Metabolic · part of Fat loss and metabolism
What did it do to blood sugar?
The best-measured area in the entire catalogue, because this is where the drug money went. Numbers here come from trials with tens of thousands of people.
170,638
people in trials
126
studies in people
8
compounds, animal or lab only
6
compounds people report on
33
trials found nothing
Measured in people
A trial that gave people the compound comes first. A study that only watched people, who happened to have more or less of something related, comes after. Both are studies in people and both are here. Only the first kind tested the thing you are asking about, and the watch-only ones are labelled. Within that, the most people come first. That is a fact about the studies, not a judgement about the compound. Counts are never added up across compounds, because the same person can be in more than one trial.
Peptides and blends
39 compounds · 69,586 people given one of themWhat this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.
- 01InsulinPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 29,691 people given it.4 reported28,250 people given it4 trials
Giving long-acting insulin early did not protect the heart, and it did not cause cancer either. 12,537 people with heart risk factors and blood sugar problems got insulin glargine or usual care, then were followed for about six years. Heart outcomes came out the same. Blood sugar dropping dangerously low was about three times more common on insulin. People on insulin gained about 1.6 kg while the others lost half a kilo. Sanofi, which sells the insulin, paid for it.
The numbers ORIGIN: 12,537 people with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance or type 2 diabetes randomised to insulin glargine or standard care, median 6.2 years. Cardiovascular outcomes were neutral (hazard ratio 1.02, 95 percent confidence interval 0.94 to 1.11). Severe hypoglycaemia was 1.00 versus 0.31 per 100 person-years, and median weight rose 1.6 kg on insulin while falling 0.5 kg on standard care. No excess cancer (hazard ratio 1.00). Funded by Sanofi.
New England Journal of Medicine, 2012· 12,537 people
Two long-acting insulins protected the heart equally, and one caused fewer dangerous lows. 7,637 people with type 2 diabetes, most already with heart or kidney disease, got degludec or glargine without knowing which. Major heart events happened in 8.5 percent against 9.3 percent, close enough to call equal. Severe low blood sugar hit 4.9 percent against 6.6 percent, about 17 fewer people in every thousand. Novo Nordisk, which sells degludec, paid for it.
The numbers DEVOTE: 7,637 people with type 2 diabetes, 85.2 percent with established cardiovascular or kidney disease, randomised double-blind to insulin degludec or glargine U100. Major cardiovascular events occurred in 8.5 versus 9.3 percent (hazard ratio 0.91, 95 percent confidence interval 0.78 to 1.06, non-inferior). Severe hypoglycaemia occurred in 4.9 versus 6.6 percent, an absolute difference of 1.7 percentage points (rate ratio 0.60, p < 0.001 for superiority). Sponsor Novo Nordisk.
New England Journal of Medicine, 2017· 7,637 people
The benefit of early tight control outlasted the control itself. 4,209 people from the original trial were followed for 10 more years. Within a year of the trial ending, blood sugar in the two groups had evened out. Ten years later the intensively treated group still had fewer diabetes complications, fewer heart attacks and fewer deaths of any cause. Those treated with metformin did better still. Once the trial ended nobody was assigned to anything, so this part is observation rather than a test.
The numbers UKPDS post-trial monitoring of 4,209 randomised participants. Glycaemic differences disappeared within a year of the trial ending, yet at 10 years the sulfonylurea-insulin group retained reductions in any diabetes-related endpoint (9 percent, p = 0.04), microvascular disease (24 percent, p = 0.001), myocardial infarction (15 percent, p = 0.01) and death from any cause (13 percent, p = 0.007). The metformin group showed larger reductions in myocardial infarction (33 percent) and death (27 percent).
New England Journal of Medicine, 2008· 4,209 people
Controlling blood sugar tightly protected the small blood vessels, and it came at a cost. 3,867 people newly diagnosed with type 2 diabetes got either tight treatment with insulin or sulfonylurea pills, or diet-first care. Over 10 years their typical long-term blood sugar ran 7.0 against 7.9 on the usual scale. Damage to eyes, kidneys and nerves was less common in the tight group. Blood sugar dropping too low was more common. This tested tight control, not insulin against pills.
The numbers 3,867 people with newly diagnosed type 2 diabetes randomised to intensive sulfonylurea or insulin therapy or to conventional diet-first treatment. Over 10 years, median HbA1c was 7.0 percent versus 7.9 percent, an 11 percent relative reduction, with reduced microvascular complications and more hypoglycaemia in the intensive group.
Lancet, 1998· 3,867 people
- 02TirzepatidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 9 completed trials, 22,802 people given it.11 reported18,111 people given it4 trials
Tirzepatide guarded the heart about as well as a drug already known to do it. More than 13,000 people with type 2 diabetes and hardened, narrowed arteries took either tirzepatide or dulaglutide. Heart attacks, strokes and deaths from heart disease happened to 12.2% of the tirzepatide group and 13.1% of the dulaglutide group. The trial was built to show tirzepatide was not worse, rather than to show it was better. It was not worse. That is what the 2026 heart licence rests on.
The numbers 13,299 patients with type 2 diabetes and atherosclerotic disease: primary MACE in 12.2% on tirzepatide vs 13.1% on dulaglutide (HR 0.92), meeting noninferiority against an active comparator with proven benefit; basis of the August 2026 cardiovascular indication.
New England Journal of Medicine, 2025· 13,299 people
Tirzepatide controlled blood sugar better than insulin and caused far fewer dangerous sugar lows. 1,995 people with type 2 diabetes and raised heart risk were treated for a year, everyone knowing which drug they got. Average blood sugar over three months fell about 2.5 points on tirzepatide and 1.44 on insulin glargine. Serious low blood sugar hit 6% to 9% on tirzepatide against 19% on insulin. Heart attacks and strokes leaned tirzepatide's way, on too few events to call.
The numbers 1,995 treated participants: HbA1c change at 52 weeks -2.43% (10 mg) and -2.58% (15 mg) versus -1.44% on glargine, with severe or clinically significant hypoglycaemia in 6% to 9% versus 19%. Adjudicated four-point MACE hazard ratio 0.74 (95% CI 0.51 to 1.08).
The Lancet, 2021· 1,995 people
Tirzepatide beat semaglutide head to head on blood sugar. Nearly 1,900 people with type 2 diabetes took one drug or the other for about nine months. Every tirzepatide dose brought average blood sugar down further than semaglutide did. People on the strongest tirzepatide dose also lost up to 5.5 kg more, which is about 12 pounds. One thing matters here. The semaglutide dose used was 1 mg, lower than the 2.4 mg dose people take for weight loss.
The numbers 1,879 patients over 40 weeks: all tirzepatide doses were noninferior and superior to semaglutide 1 mg for HbA1c, with greater weight loss (up to -5.5 kg more at 15 mg).
New England Journal of Medicine, 2021· 1,879 people
Tirzepatide produced large weight loss in people who also had type 2 diabetes. 938 adults took the weekly shot or a dummy one for 72 weeks, and nobody involved knew which. Those on the drug lost about 12.8% of their body weight at the middle dose and 14.7% at the top dose. The dummy group lost 3.2%. Around eight in ten on the drug lost at least 5% of their weight, against three in ten on the dummy.
The numbers 938 adults with obesity and type 2 diabetes over 72 weeks: least-squares mean weight change -12.8% (10 mg) and -14.7% (15 mg) versus -3.2% on placebo; 79% to 83% versus 32% lost at least 5%.
The Lancet, 2023· 938 people
- 03LiraglutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 6 completed trials, 16,760 people given it.9 reported10,186 people given it2 trials
Liraglutide cut heart attacks, strokes and deaths from heart disease in people with diabetes. 9,340 adults with type 2 diabetes and a high risk of heart trouble got either liraglutide or a dummy injection, and were followed for close to four years. About one in eight fewer of those events happened on the drug. In plain counts that is roughly 19 fewer heart attacks, strokes and cardiac deaths for every 1,000 people treated. Everyone here already had diabetes, so it says nothing about healthy people.
The numbers 9,340 patients with type 2 diabetes at high cardiovascular risk, median 3.8 years: primary MACE in 13.0% on liraglutide vs 14.9% on placebo (HR 0.87, a 13% relative reduction; P=0.01 for superiority).
New England Journal of Medicine, 2016· 9,340 people
Liraglutide took off a modest amount of weight in people with type 2 diabetes. 846 adults took the daily shot at one of two doses or a dummy one for 56 weeks. Nobody involved knew which. The higher dose took off 6.0% of body weight, the lower dose 4.7%, and the dummy 2.0%. A quarter of the people on the higher dose lost more than a tenth of their weight, against under seven in a hundred on the dummy.
The numbers 846 adults with overweight or obesity and type 2 diabetes over 56 weeks: weight loss 6.0% on liraglutide 3.0 mg and 4.7% on 1.8 mg versus 2.0% on placebo, with more than 10% lost by 25.2% versus 6.7%.
JAMA, 2015· 846 people
- 04TaspoglutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 2,181 people given it.2,181 people given it3 trials
Taspoglutide controlled blood sugar better than exenatide and made far more people sick. 1,189 overweight adults with diabetes were split by chance across two taspoglutide doses or twice-daily exenatide for six months, and everybody knew which. Average blood sugar fell more on taspoglutide. Weight loss was no better. Nausea hit over half on taspoglutide against a third on exenatide, and a third vomited. More people quit, and nearly half developed antibodies to the drug. The sponsor paid.
The numbers 1,189 overweight adults with type 2 diabetes on metformin randomised open-label to taspoglutide 10 mg weekly (399), 20 mg weekly (398) or exenatide 10 mcg twice daily (392), 24 weeks. HbA1c minus 1.24 and minus 1.31 percentage points against minus 0.98 (P below 0.0001 for both). Weight minus 1.6 and minus 2.3 kg against minus 2.3 kg. Nausea 53, 59 and 35 percent; vomiting 33, 37 and 16 percent; more allergic and injection site reactions and more discontinuations with taspoglutide; anti-drug antibodies in 49 percent. Sponsor funded (registry NCT00717457).
Diabetes Care, 2013· 1,189 people
Taspoglutide beat sitagliptin on blood sugar and weight, and the safety picture ended the drug. 666 people on metformin were split by chance across two taspoglutide doses, sitagliptin, or a dummy, for six months. Nobody involved knew which. Blood sugar and weight both fell further on taspoglutide. Stomach trouble, allergic reactions and injection site reactions were all worse, and more people quit. Nearly half developed antibodies. The authors say plainly that the safety profile is why dosing was stopped.
The numbers 666 people on metformin randomised double-blind to taspoglutide 10 mg (190) or 20 mg (198) weekly, sitagliptin 100 mg daily (185) or placebo (93), 24 weeks. HbA1c minus 1.23 and minus 1.30 points against minus 0.89 (sitagliptin) and minus 0.10 (placebo); weight minus 1.8 and minus 2.6 kg against minus 0.9 and minus 0.5 kg. Gastrointestinal, allergic and injection site reactions higher with taspoglutide with higher discontinuation; antibodies confirmed in 46 percent. The authors state the safety profile led to discontinuation of dosing. Sponsor funded.
Diabetes Therapy, 2012· 666 people
Taspoglutide lowered blood sugar well on top of two other diabetes drugs, and the side effects were brutal. 326 people were split by chance between two doses and a dummy for six months. Nobody involved knew which. Average blood sugar fell by well over a point against under half a point on the dummy, and most people reached target. Weight barely moved. Nausea hit a third to nearly half, a fifth to a quarter vomited, and a quarter had injection site reactions. The sponsor paid.
The numbers 326 people randomised double-blind to taspoglutide 10 mg, 20 mg or placebo weekly for 24 weeks. HbA1c minus 1.35 and minus 1.40 points against minus 0.45 (P below 0.0001); HbA1c at or below 7 percent in 69.8 and 76.1 percent against 35.1; weight minus 0.64 and minus 1.04 kg against plus 0.59 kg. Nausea 35, 44 and 10 percent; vomiting 21, 24 and 2 percent; injection site reactions 24, 24 and 5 percent. Sponsor funded.
Journal of Clinical Endocrinology and Metabolism, 2012· 326 people
- 05MazdutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 2,372 people given it.7 reported1,301 people given it3 trials
Head to head against an established diabetes drug, mazdutide won on both blood sugar and weight. Seven hundred and thirty-one Chinese adults with type 2 diabetes were given mazdutide at one of two doses or dulaglutide for about seven months. Both mazdutide doses lowered average blood sugar more than dulaglutide did. They also took off 3.8 to 5.8 percentage points more body weight. The dulaglutide dose used was 1.5 mg, which is not the highest dose that drug is licensed at.
The numbers Phase 3 in 731 adults: both mazdutide doses were superior to dulaglutide 1.5 mg for HbA1c and produced 3.8 to 5.8 percentage points more weight loss at 28 weeks.
Nature, 2026· 731 people
Mazdutide on its own lowered blood sugar sharply in a late-stage Chinese trial. 320 people with type 2 diabetes took one of two doses or a dummy shot for 24 weeks. Average blood sugar over three months fell 1.57 points on the lower dose and 2.15 on the higher, against 0.14 on the dummy. Weight fell 5.61% and 7.81%, against 1.26%. Everyone was recruited in China, so the percentages may not carry over to other populations.
The numbers Phase 3 monotherapy in 320 participants: HbA1c -1.57% (4 mg) and -2.15% (6 mg) versus -0.14% on placebo at week 24, and weight -5.61% and -7.81% versus -1.26%.
Nature, 2026· 320 people
Mazdutide beat a dummy shot on blood sugar and edged an older drug, in a short mid-stage trial. 250 Chinese adults with type 2 diabetes were treated for 20 weeks. Average blood sugar over three months fell between 1.41 and 1.67 points across mazdutide doses, against 1.35 on dulaglutide and no change at all on the dummy. Weight fell up to 7.1%. Low blood sugar was reported by 10% against 8% on the dummy. Twenty weeks is a short look.
The numbers 250 adults over 20 weeks: HbA1c -1.41% to -1.67% across mazdutide doses versus -1.35% on dulaglutide and +0.03% on placebo, with weight change up to -7.1%. Hypoglycaemia 10% versus 8% on placebo.
Diabetes Care, 2024· 250 people
- 06CagrilintidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 5,752 people given it.7 reported1,298 people given it2 trials
In a large late-stage trial the pair took off substantial weight and pulled most people's blood sugar into range. 1,206 adults with extra weight and type 2 diabetes took CagriSema or a dummy injection for about sixteen months. Body weight fell 13.7% on the drug and 3.4% on the dummy. Nearly three quarters got their average blood sugar down to 6.5% or lower. Everyone in this trial had diabetes. Sixteen months is a long trial and still says nothing about a decade.
The numbers Phase 3a, 1,206 patients: -13.7% body weight at 68 weeks with CagriSema vs -3.4% with placebo; 73.5% reached HbA1c of 6.5% or lower.
New England Journal of Medicine, 2025· 1,206 people
Adding cagrilintide to semaglutide roughly doubled weight loss in a small early trial. 92 adults with type 2 diabetes took the pair, or semaglutide alone, or cagrilintide alone, for eight months. The pair took off 15.6% of body weight. Semaglutide alone took off 5.1% and cagrilintide alone 8.1%. This was an early study in fewer than a hundred people, all of them diabetic. It is far too small to tell you how often the side effects happen or who they happen to.
The numbers 92 adults with type 2 diabetes over 32 weeks: body weight change of -15.6% with CagriSema vs -5.1% with semaglutide alone and -8.1% with cagrilintide alone (NCT04982575).
The Lancet, 2023· 92 people
- 07SemaglutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 12 completed trials, 42,363 people given it.10 reported1,210 people given it1 trial, 1 watch-only
A single eye clinic reported far more cases of a sudden blinding optic nerve stroke among its semaglutide patients. Nobody was given anything. Researchers looked back through records at one specialist clinic for eye nerve problems, covering 16,827 patients. Over three years the condition appeared in 8.9% of semaglutide patients with diabetes against 1.8% of others, and 6.7% against 0.8% among those treated for weight. This clinic has such cases referred to it, so its patients are not typical, and it cannot show the drug caused this.
The numbers Retrospective matched cohort at one neuro-ophthalmology practice, 16,827 patients screened: 36-month cumulative NAION incidence 8.9% versus 1.8% in type 2 diabetes (HR 4.28) and 6.7% versus 0.8% in overweight or obesity (HR 7.64). Observational, referral population, causality not established.
JAMA Ophthalmology, 2024· 16,827 peopleobserved only, nobody was given it
Semaglutide still worked when people also had diabetes, though the weight loss was smaller. About 1,200 adults with extra weight and type 2 diabetes got the weekly shot or a dummy one, and nobody involved knew which. After 68 weeks the drug group had lost about a tenth of their body weight and the dummy group about 3%. Roughly seven in ten on the drug lost at least 5% of their weight, against under three in ten.
The numbers 1,210 adults with overweight or obesity and type 2 diabetes: estimated body weight change -9.6% on semaglutide 2.4 mg versus -3.4% on placebo at 68 weeks; 68.8% versus 28.5% lost at least 5%.
The Lancet, 2021· 1,210 people
- 08CagriSemaPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 4,954 people given it.8 reported1,206 people given it1 trial
The same combination worked in people who also had type 2 diabetes, and it worked less well. 1,206 patients took it or a dummy for about 16 months. They lost close to 14 percent of their weight, against roughly 3 percent on the dummy. Weight drugs reliably do less in diabetes than outside it, and this is that pattern again. Less than a fifth is still a great deal of weight.
The numbers 1,206 patients with type 2 diabetes: 13.7% weight loss at 68 weeks versus 3.4% with placebo.
New England Journal of Medicine, 2025· 1,206 people
- 09CotadutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 6 completed trials, 1,221 people given it.1,147 people given it3 trials
Cotadutide lowered blood sugar and weight in people with diabetes, and it beat liraglutide on weight at the top dose. 834 adults on metformin were split by chance across three doses, a dummy, or liraglutide, for about a year. Blood sugar and weight both fell against the dummy. At the highest dose, liver enzymes and scarring scores improved, which liraglutide did not manage. Nausea hit about a third and vomiting about one in six. AstraZeneca funded it.
The numbers 834 adults with type 2 diabetes and BMI 25 or more on metformin, randomised to cotadutide 100 mcg (100), 200 mcg (256) or 300 mcg (256), placebo (110) or open-label liraglutide 1.8 mg (110) for 54 weeks. HbA1c and weight fell against placebo at weeks 14 and 54 (all P below 0.001). Weight loss at 300 mcg exceeded liraglutide; liver enzymes and fibrosis scores improved at 300 mcg but not with liraglutide. Nausea 35 percent, vomiting 17 percent. Funded by AstraZeneca (registry NCT03235050, results posted 2020).
Diabetes Care, 2021· 834 people
Cotadutide sharply cut protein leaking into the urine in diabetic kidney disease. 248 people with type 2 diabetes and kidney damage were split by chance across three doses, a dummy, or semaglutide, for about six months. Protein in the urine fell by roughly half at the two higher doses, and the fall held. Serious side effects were balanced across groups. Protein in the urine is a marker, not a kidney that has been saved. Nobody was followed long enough to see kidney failure. The sponsor paid.
The numbers 248 people with type 2 diabetes and chronic kidney disease (mean eGFR 55, 47 percent on SGLT2 inhibitors), 26 weeks, randomised to cotadutide 100, 300 or 600 mcg, placebo, or open-label semaglutide 1 mg weekly. Urine albumin to creatinine ratio fell 43.9 percent at 300 mcg (95 percent CI 30.6 to 54.7) and 49.9 percent at 600 mcg (38.4 to 59.3) against placebo at week 14, sustained to week 26. Serious adverse events balanced; tolerability at 600 mcg described as comparable to semaglutide. Sponsor funded (NCT04515849, results posted January 2025).
Kidney International, 2024· 248 people
An early trial showed cotadutide blunts the blood sugar spike after a meal, and takes off some weight. 65 adults with diabetes and extra weight took it daily for seven weeks, or a dummy. After meals, blood sugar rose about a fifth less, while it climbed on the dummy. Weight fell about three and a half percent, against almost nothing on the dummy. The stomach emptied roughly two hours more slowly. Seven weeks tells you about the mechanism, not about living with the drug. The sponsor paid.
The numbers Phase 2a, 65 adults with type 2 diabetes and overweight or obesity, 49 days of daily cotadutide (50 to 300 mcg) or placebo. Postprandial glucose area under the curve fell 21.5 percent against a 6.3 percent rise on placebo (P below 0.001); weight fell 3.41 percent against 0.08 percent (P equals 0.002); postprandial insulin rose and gastric emptying half-time lengthened by about two hours. Sponsor funded.
Journal of Clinical Endocrinology and Metabolism, 2020· 65 people
- 10RetatrutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,345 people given it.8 reported818 people given it2 trials
This is the first full late-stage report for retatrutide, and it holds up. 537 people with type 2 diabetes not controlled by diet and exercise took the drug or a dummy shot for 40 weeks. Nobody involved knew which. Average blood sugar over three months fell between 1.69 and 1.94 points across the doses, against 0.81 on the dummy. Weight fell between 11.5% and 15.3%, against 2.6%. This is a diabetes trial, not the obesity trials everyone is waiting for.
The numbers 537 participants over 40 weeks (NCT06354660): HbA1c -1.69% to -1.94% across doses versus -0.81% on placebo, and body weight -11.5% to -15.3% versus -2.6%. The first fully published Phase 3 result for retatrutide.
The Lancet, 2026· 537 people
Retatrutide lowered blood sugar and weight more than an older drug, in a mid-stage trial. 281 people with type 2 diabetes were split by chance between retatrutide, dulaglutide and a dummy shot, and nobody involved knew which. At the top dose, average blood sugar over three months fell about 2 points, against almost nothing on the dummy and 1.41 on dulaglutide. Weight fell 16.94% against 3.00%. Nobody had a severe sugar low and nobody died. It ran under a year.
The numbers 281 randomized, 275 analysed (NCT04867785): HbA1c -2.02% at 12 mg versus -0.01% on placebo and -1.41% on dulaglutide at 24 weeks; body weight -16.94% versus -3.00% and -2.02% at 36 weeks. No severe hypoglycaemia and no deaths.
The Lancet, 2023· 281 people
- 11AmylinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 651 people given it.4 reported651 people given it1 trial
It worked, and the benefit was modest. 651 people with type 1 diabetes took pramlintide with their insulin, or a dummy shot, for a year. Their average blood sugar over three months fell by about a third of a point. On the dummy it barely moved. Weight control also got better. A third of a point is a real difference and a small one. This page says so rather than rounding it up.
The numbers 651 people with type 1 diabetes, 52 weeks, randomised. HbA1c fell 0.29 to 0.34 percentage points against 0.04 on placebo. Statistically clear and clinically modest, and the page says so rather than rounding it up.
Diabetic Medicine, 2004· 651 people
- 12PEG-loxenatidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 590 people given it.590 people given it4 trials2 found nothing
On its own it lowered blood sugar clearly, and the higher dose brought more sickness. 361 Chinese patients whose blood sugar was not under control were split by chance to a dummy, 100 or 200 micrograms weekly for 24 weeks. Average blood sugar fell 1.02 and 1.34 points against 0.17 on the dummy. 34.7 and 46.6 percent got below 7 percent against 15.7 percent. Nausea hit 5.6 and 10.0 percent against nobody on the dummy, and vomiting 2.4 and 8.3 percent against nobody. 4 patients made antibodies.
The numbers 361 Chinese patients with inadequate glycaemic control randomised to placebo, 100 or 200 micrograms weekly for 24 weeks, then a 28 week extension. Glycated haemoglobin fell 1.02 percentage points on 100 micrograms and 1.34 on 200 against 0.17 on placebo. 34.7 percent and 46.6 percent reached below 7 percent against 15.7 percent. Nausea occurred in 5.6 and 10.0 percent against none on placebo, vomiting in 2.4 and 8.3 percent against none. Antidrug antibodies developed in 4 patients, 1.2 percent.
Diabetes, Obesity and Metabolism, 2021· 361 people
Very high doses took off a lot of weight, and this trial cannot carry that. 123 enrolled at one centre and 105 finished, split by chance to 300 or 400 micrograms weekly or a dummy. Weight fell 16.34 kg and 21.14 kg against 6.75 kg. Side effects hit 36.11 percent on the high dose against 11.43 percent. Here is the problem. The doses run up to four times the registered ones, only patients were kept in the dark, and the dummy group lost 6.75 kg, so everyone was dieting hard.
The numbers Single-centre, single-blind trial, 123 enrolled and 105 completed, randomised to 300 or 400 micrograms weekly or placebo for 24 weeks. Weight fell 16.34 kg on 300 micrograms and 21.14 kg on 400 against 6.75 kg on placebo. Glycated haemoglobin fell 1.02 and 1.34 percentage points against 0.50. Adverse drug reactions reached 36.11 percent on the high dose against 11.43 percent on placebo. These doses are one and a half to four times the registration doses, the trial is single-centre and single-blind, and the placebo arm losing 6.75 kg indicates a substantial background intervention in all groups.
Frontiers in Endocrinology, 2026· 123 people
found nothingIt matched the comparison drug on a urine marker, and no actual kidney outcome was measured. 106 people at one centre were assigned by chance and everybody knew what they were taking. 80 finished. Over 24 weeks, protein leaking into the urine fell 29.3 percent on PEG-loxenatide and 31.8 percent on dapagliflozin, a gap too small to call. Average blood sugar fell almost identically. Stomach side effects were more common on PEG-loxenatide. Protein in the urine is a marker. Nobody counted dialysis, transplants or failing kidneys.
The numbers Single-centre open-label trial against dapagliflozin. 106 randomised, 80 completed. Urine albumin to creatinine ratio fell 29.3 percent on PEG-loxenatide against 31.8 percent on dapagliflozin over 24 weeks, a difference that was not significant. Glycated haemoglobin fell almost identically in both arms. Triglycerides fell more on PEG-loxenatide. Gastrointestinal adverse events were more common on PEG-loxenatide. Albuminuria is a surrogate marker; no kidney outcome such as dialysis, transplantation or doubling of creatinine was measured.
Frontiers in Endocrinology, 2024· 106 people
found nothingAdded to metformin it worked, and doubling the dose added nothing. Across 44 Chinese sites patients took metformin plus a dummy, plus 100 micrograms, or plus 200 micrograms, for 24 weeks. Average blood sugar fell 1.16 and 1.14 points on the two doses, while the dummy group's rose 0.35. 37.4 and 40.6 percent got below 7.0 percent against 16.8 percent. The two doses came out the same, so there is no case for the bigger one. Stomach reactions were mild, and under 2 percent made antibodies.
The numbers The add-on registration trial across 44 Chinese sites, randomised to metformin plus placebo, plus 100 micrograms or plus 200 micrograms, 24 weeks core plus 28 week extension. Glycated haemoglobin fell 1.16 and 1.14 percentage points against a rise of 0.35 on placebo. 37.4 and 40.6 percent reached below 7.0 percent against 16.8 percent. Notably the two doses performed the same, gastrointestinal reactions were mild, hypoglycaemia and weight gain did not increase, anti-drug antibodies appeared in under 2 percent, and no treatment-emergent serious adverse events occurred.
Diabetes, Obesity and Metabolism, 2020· number of people not given
- 13VisepegenatidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 572 people given it.560 people given it3 trials1 found nothing
It lowered blood sugar in people newly treated for diabetes, and the weight number needs care. 273 adults who had never been treated were split evenly by chance to 150 micrograms weekly or a dummy for 24 weeks. Average blood sugar fell 1.36 points against 0.63. 50.4 percent got below 7.0 percent against 14.2 percent. 3 people on the drug needed rescue treatment against 17 on the dummy. The 4.77 kg weight loss at week 52 varied so widely that it should not be read as typical. PegBio funded it.
The numbers 273 treatment-naive adults at 30 Chinese centres, randomised 1:1 to 150 micrograms weekly or placebo for 24 weeks, then all on active drug to week 52. At week 24 glycated haemoglobin fell 1.36 percentage points against 0.63 on placebo, a difference of 0.73 points. 50.4 percent reached below 7.0 percent against 14.2 percent. Rescue therapy was needed by 3 participants on drug against 17 on placebo. Weight loss was reported as BMI-dependent and reached 4.77 kg at week 52 in those with BMI above 32, with a standard deviation of 13.94 kg, which is wide enough to warrant caution. Funded by PegBio.
The Lancet Regional Health Western Pacific, 2024· 273 people
The middle dose beat the highest one, which is why the middle dose went forward. 251 Chinese patients who had never been treated got a dummy or 75, 150 or 200 micrograms weekly for 12 weeks. Average blood sugar over three months fell further than the dummy group by 0.72, 1.18 and 1.02 points. Nobody had a serious drug-related event, severe low blood sugar, or died. One thing to know before quoting it: this paper has a published correction.
The numbers 251 treatment-naive Chinese patients randomised to placebo or 75, 150 or 200 micrograms weekly for 12 weeks. Glycated haemoglobin differences against placebo were 0.72, 1.18 and 1.02 percentage points, with the middle dose performing best rather than the highest, which is why 150 micrograms went forward. No treatment-emergent serious adverse event, severe hypoglycaemia or death. Note that this paper has a published correction.
Diabetologia, 2021· 251 people
found nothingA mechanism study in 36 people, and the plainest measure of insulin resistance did not budge. The patients got 25 or 50 micrograms weekly, or twice-daily exenatide, for 12 weeks. Meal tests were used to model how the pancreas and body handled insulin. Both treatments improved pancreas function against each group's own starting point. The high dose improved a modelled insulin sensitivity measure. The standard measure of insulin resistance showed no change, within groups or between them. This was built to look at biology, not benefit.
The numbers 36 Chinese patients randomised to 25 or 50 micrograms weekly or to twice-daily exenatide for 12 weeks, with oral mixed meal tolerance tests modelled to estimate beta cell function and insulin sensitivity. Both treatments raised beta cell function parameters, disposition index and insulin secretion rates against their own baseline. The high dose improved a modelled insulin sensitivity parameter, but the simpler homeostatic model assessment of insulin resistance showed no significant change within or between treatments. A 36 person mechanistic study, not an efficacy trial.
Frontiers in Pharmacology, 2023· 36 people
- 14PramlintidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 684 people given it.480 people given it2 trials, 1 watch-only
Pramlintide improved blood sugar control in type 1 diabetes, and people lost weight instead of gaining it. Four hundred and eighty patients were treated alongside their insulin for a year. At three months, average blood sugar had fallen by 0.67 percentage points on the drug and 0.16 on a dummy injection. Severe low blood sugar episodes did not become more frequent. The improvement is real but modest, and it is a blood number rather than a count of complications avoided.
The numbers 52-week trial in 480 patients with type 1 diabetes: pramlintide lowered HbA1c by 0.67% versus 0.16% for placebo at week 13, with weight loss rather than gain and no rise in severe hypoglycemia.
Diabetes Care, 2002· 480 people
In type 2 diabetes the benefit is real but small. Researchers pooled two long trials of overweight and obese patients who were already on insulin. After six months, the drug groups had about 0.41 percentage points lower average blood sugar than the dummy groups, and were 1.8 kg lighter. They also needed less insulin. Pooling two finished trials is not the same as running a new one, and 1.8 kg over six months is a modest return for a daily injection.
The numbers Pooled analysis of two long-term trials: placebo-corrected reductions of 0.41% in HbA1c and 1.8 kg in weight at 26 weeks, with lower insulin use.
Obesity Research, 2004· number of people not given
This is the regulator's instruction sheet, not a study. It approves pramlintide only as an add on to insulin taken at meals, in both type 1 and type 2 diabetes. It carries the strongest warning the regulator issues, because combining it with insulin can drop blood sugar dangerously low. To manage that, the label tells doctors to halve the mealtime insulin dose when starting. It is not approved as a weight loss drug, and it is not meant to be used alone.
The numbers FDA-approved label: adjunct to mealtime insulin in type 1 and type 2 diabetes; boxed warning for severe insulin-induced hypoglycemia and a 50% mealtime insulin reduction at initiation.
U.S. FDA (Drugs@FDA label), 2015· number of people not givenobserved only, nobody was given itpoints the wrong way
- 15SurvodutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 2,034 people given it.7 reported413 people given it1 trial
Against semaglutide, survodutide matched it on blood sugar, beat it on weight, and cost more in side effects. The trial put 413 people with type 2 diabetes on one of six survodutide doses, on semaglutide, or on a dummy injection for four months. Average blood sugar fell by about the same amount on both drugs. Weight fell further on the highest survodutide dose. Side effects hit around three quarters on survodutide and about half on semaglutide. Everyone knew who was getting semaglutide.
The numbers 413 randomized over 16 weeks: HbA1c fell 1.46% on low-dose survodutide against 1.47% on open-label semaglutide, while weight fell up to 8.7% on the highest survodutide dose against 5.3% on semaglutide. Adverse events 77.8% against 52.0%.
Diabetologia, 2024· 413 people
- 16ExenatidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 15,088 people given it.1 reported336 people given it1 trial
Exenatide lowered blood sugar and took off a little weight in people already on metformin. 336 patients at 82 US clinics added exenatide or a dummy injection twice a day for seven months. Average blood sugar over three months fell about three quarters of a point on the higher dose and four tenths on the lower one. On the dummy it drifted slightly upward. Weight fell by up to 2.8 kg, more at the higher dose. Seven months is too short to tell you about years of use.
The numbers 336 patients at 82 US sites: HbA1c fell 0.78% (10 mcg twice daily) and 0.40% (5 mcg) versus a 0.08% rise on placebo, with dose-dependent weight loss of up to 2.8 kg.
Diabetes Care, 2005· 336 people
- 17BofanglutidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 750 people given it.4 reported272 people given it1 trial
It matched semaglutide on blood sugar and cost people far more stomach trouble. 272 adults with type 2 diabetes at 37 Chinese hospitals took bofanglutide or semaglutide, and everybody knew which. By week 24 average blood sugar had fallen 1.87 to 2.32 points on bofanglutide, against 1.60 on semaglutide. Stomach side effects hit 82 to 87 percent of the bofanglutide groups against 52 percent on semaglutide. Low blood sugar stayed rare. The trial was short, everyone was Chinese, and the maker paid for it.
The numbers Open-label phase 2b trial at 37 Chinese sites, 272 adults with type 2 diabetes, mean baseline glycated haemoglobin 8.35 percent. At week 24 the change from baseline was minus 1.87, minus 2.28 and minus 1.94 percentage points for bofanglutide 12, 18 and 24 mg every two weeks, minus 2.32 for 24 mg weekly, and minus 1.60 for semaglutide 1 mg weekly. Gastrointestinal adverse events, mostly grade 1 or 2, occurred in 81.8 to 87.3 percent of bofanglutide participants against 51.9 percent on semaglutide. Hypoglycaemia occurred in 0 to 3.8 percent versus 1.9 percent, none severe. The authors list open-label design, short duration and an all-Chinese population as limitations. Funded by Gan and Lee Pharmaceuticals.
Annals of Internal Medicine, 2026· 272 people
- 18TesamorelinPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 8 completed trials, 1,729 people given it.10 reported149 people given it3 trials1 found nothing
found nothingIt worked on liver fat, in a small trial. 61 people with HIV and a fatty liver were split evenly and given a daily injection of tesamorelin or a dummy version for a year. Nobody involved knew which. Liver fat came down by about a third more on tesamorelin than on the dummy. By the end 35% of the tesamorelin group had liver fat back under the normal threshold, against 4% on the dummy. With 61 people this is a first answer, not a settled one.
The numbers 61 people with HIV and NAFLD (NCT02196831) randomized 30 to 30 to 12 months of tesamorelin 2 mg daily or placebo, with hepatic fat fraction as the primary endpoint. Hepatic fat fraction fell further on tesamorelin, absolute effect minus 4.1 percent (95% CI minus 7.6 to minus 0.7, p = 0.018), a minus 37 percent relative reduction (95% CI minus 67 to minus 7, p = 0.016). At 12 months 35 percent on tesamorelin and 4 percent on placebo had a hepatic fat fraction under 5 percent (p = 0.0069). Fasting glucose and glycated haemoglobin did not differ between groups. Injection site complaints were more common on tesamorelin, none judged serious.
The Lancet HIV, 2019· 61 people
Tesamorelin shrank both deep belly fat and liver fat, in a small trial. 50 people with HIV and belly fat were split by chance, and 48 were treated for six months. Deep fat around the organs fell 42 cm2 more than on the dummy shot, and liver fat fell about 3 percentage points more. Fasting blood sugar rose 7 mg/dL more than the dummy in the first two weeks. By six months that blood sugar difference had gone.
The numbers 50 randomized, 48 treated over 6 months: visceral fat treatment effect -42 cm2 (95% CI -71 to -14) and net liver fat -2.9% lipid-to-water. Fasting glucose rose 7 mg/dL more than placebo at 2 weeks.
JAMA, 2014· 50 people
The drug still worked in people taking the newer HIV medicines that tend to add weight. 38 of the 61 people in this trial were on integrase inhibitors, and 31 finished the year. Their deep belly fat fell about 25 cm2 while it rose about 14 cm2 on the dummy shot, and liver fat fell 4.2% against 0.5%. Blood sugar control did not get worse. This is a slice of a small trial, not a trial of its own.
The numbers 38 participants on integrase-inhibitor regimens within a 61-person randomized trial, 31 completing 12 months: median visceral fat -25 cm2 versus +14 cm2 and hepatic fat -4.2% versus -0.5%, without worsening glycemic control.
AIDS, 2024· 38 peoplepoints the wrong way
- 19EfinopegdutidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 145 people given it.145 people given it1 trial1 found nothing
found nothingA dual-acting drug cleared far more liver fat than semaglutide in a head to head test. 145 people with fatty liver disease were split by chance between the two drugs for about six months. Everybody knew which drug they were taking. Liver fat fell by roughly three quarters on efinopegdutide against a little over two fifths on semaglutide. Weight loss was similar. Liver fat on a scan is a marker. Nobody here was followed long enough to see scarring, liver failure or death.
The numbers 145 participants with liver fat content of 10 percent or more, randomised 1:1 to efinopegdutide 10 mg or semaglutide 1 mg weekly for 24 weeks, open-label. Mean baseline BMI 34.3 and liver fat 20.3 percent; 33.1 percent had type 2 diabetes. Relative reduction in liver fat 72.7 percent (90% CI 66.8 to 78.7) against 42.3 percent (90% CI 36.5 to 48.1), p < 0.001. Body weight reduction 8.5 percent against 7.1 percent, p = 0.085, not significant. Slightly higher adverse events on efinopegdutide, mainly gastrointestinal.
Journal of Hepatology, 2023· 145 people
- 20CT-868PeptideModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 103 people given it.103 people given it1 trial
Blood sugar fell a long way and weight barely moved, which is unusual for this drug class. 103 adults with type 2 diabetes took CT-868 daily at 1.75 mg, 4.0 mg or a dummy for 26 weeks, nobody knowing which. Average blood sugar fell 1.61 to 2.24 points further than the dummy group. Weight fell only 2.9 percent further on the higher dose. Covid supply problems meant some on the higher dose got less and were counted separately. Most authors work or worked for Roche or Carmot.
The numbers 26 week phase 2 in 103 adults with type 2 diabetes, body mass index at least 27 and glycated haemoglobin 7.0 to 10.0 percent, randomised to once-daily CT-868 1.75 mg, 4.0 mg or placebo. Glycated haemoglobin fell 1.61 to 2.24 percentage points against placebo. Body weight fell only 2.9 percent against placebo on 4.0 mg. Fasting glucose, self-monitored glucose and most lipid parameters improved. No participant experienced hypoglycaemia. COVID-19 supply constraints meant some participants assigned 4.0 mg received a maximum of 3.25 mg and were analysed as a separate arm. Most authors are current or former Roche or Carmot employees.
Diabetes, Obesity and Metabolism, 2026· 103 people
- 21GlucagonPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 141 people given it.3 reported75 people given it1 trial
A puff up the nose rescued dangerously low blood sugar as well as an injection into the muscle did. 75 Japanese adults with type 1 or type 2 diabetes had their blood sugar deliberately driven low under supervision, then received both treatments in turn. Every single patient recovered on both routes. Blood sugar rose along much the same path for the first hour either way. The spray brought some nose pain, and both routes brought nausea and vomiting. Everyone knew which treatment they were getting each time.
The numbers 75 adults with type 1 or type 2 diabetes underwent insulin-induced hypoglycemia and received nasal or intramuscular glucagon in crossover. The endpoint was the proportion reaching a plasma glucose of 3.9 mmol/L or a 1.1 mmol/L rise from nadir within 30 minutes, tested for non-inferiority.
Diabetes, Obesity and Metabolism, 2020· 75 people
- 22BGM0504PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 64 people given it.64 people given it1 trial
This is a twelve-people-per-group signal, and its authors call it that. 64 Chinese adults with type 2 diabetes took BGM0504 at 5, 10 or 15 mg, a dummy, or semaglutide, weekly for 12 weeks. Average blood sugar fell 1.72, 1.94 and 2.48 points on the three doses, against 1.43 on semaglutide and 0.28 higher on the dummy. The top dose took off more weight than semaglutide. Twelve people per group over twelve weeks cannot settle a comparison. Five authors work for BrightGene and may hold its stock.
The numbers 64 Chinese adults with type 2 diabetes randomised to BGM0504 at 5, 10 or 15 mg, placebo, or semaglutide 1 mg, all weekly for 12 weeks. Mean glycated haemoglobin change was minus 1.72, minus 1.94 and minus 2.48 percentage points against minus 1.43 for semaglutide and plus 0.28 for placebo. The 15 mg dose showed greater weight reduction than semaglutide. The authors describe the findings as a signal throughout, which is appropriate for 12 participants per arm over 12 weeks. Five authors are BrightGene employees who may hold stock.
Diabetes, Obesity and Metabolism, 2026· 64 people
- 23SermorelinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 139 people given it.8 reported19 people given it1 trial1 found nothing
found nothingThe hormone response faded while the injections carried on. Nineteen adults aged 55 to 71 injected salt water nightly for a month, then a sermorelin-like peptide for four more months. Growth hormone and its main blood marker rose within two weeks, stayed up for three months, then drifted back to where they started even though dosing never stopped. Muscle, insulin response, mood and libido improved in the men and not the women. Bone density and sleep did not change in anyone.
The numbers 19 adults aged 55 to 71 on 4 weeks of placebo then 16 weeks of the Nle27 analogue at 10 micrograms/kg nightly: IGF-1 and IGFBP-3 rose within 2 weeks and returned toward baseline by week 16 while dosing continued. Lean mass, insulin sensitivity, well-being and libido improved in men only; bone mineral density and sleep quality did not change.
Journal of Clinical Endocrinology and Metabolism, 1997· 19 people
- 24GalaninPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 21 people given it.13 people given it2 trials2 found nothing
found nothingGalanin shuts down insulin in dogs and rodents, and in people it did nothing of the kind. Seven healthy men were given a sugar load on its own, and again with galanin at two high infusion rates. Blood sugar and insulin came out the same either way, though growth hormone still rose. The authors' own conclusion is the lesson of this entry. Be careful assuming that what a peptide does in an animal is what it will do in you.
The numbers Seven healthy male volunteers given an intravenous glucose tolerance test alone and with porcine galanin at 80 and 160 pmol/kg per minute. Galanin inhibits glucose-stimulated insulin release in dogs and rodents; in humans it had no effect on plasma glucose or serum insulin, though growth hormone still rose. The authors' explicit conclusion is that caution should be exercised in extrapolating a physiological role for galanin in humans from animal results, which is the central lesson of this entry.
Diabetes, 1989· 7 people
found nothingHuman galanin drove growth hormone up eightfold and left the pancreas completely alone. Six healthy volunteers were infused for an hour while their blood sugar was deliberately held high. Insulin, glucagon and blood sugar behaved exactly as they had without it. The body cleared half the galanin in under four minutes, which is very fast indeed. So this is a powerful growth hormone signal and, at these levels, has nothing to do with blood sugar control.
The numbers Human galanin, not porcine, infused at 74 pmol/kg per minute for 60 minutes into six healthy volunteers during a hyperglycaemic clamp. Galanin concentrations plateaued around 1500 pmol/L against pre-infusion levels of 20 to 30 pmol/L. Growth hormone rose eightfold. Insulin, C-peptide, glucagon and glucose curves were indistinguishable from control. Galanin was eliminated from plasma with a half-life of 3.7 plus or minus 0.4 minutes. The authors conclude that human galanin powerfully stimulates growth hormone secretion in man but has no effect on pancreatic endocrine secretion or glucose metabolism at these concentrations.
Diabetologia, 1993· 6 people
- 25GLP-1PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 8 people given it.1 reported8 people given it1 trial
The natural hormone brought blood sugar back to normal after major surgery. Eight people with type 2 diabetes were treated twice, once with a GLP-1 drip and once with a dummy. On the hormone, blood sugar reached the normal fasting range within about two and a half hours. On the dummy it did not. Insulin rose, glucagon fell, and nobody's blood sugar dropped too low. Eight people is about as small as a trial gets, and this was hours in a hospital, not a treatment.
The numbers Randomized crossover in eight patients with type 2 diabetes after major surgery. An eight-hour infusion of native GLP-1 brought plasma glucose into the normoglycemic fasting range within 150 minutes while placebo did not, raising insulin and C-peptide and suppressing glucagon, with no hypoglycemic events.
Critical Care Medicine, 2004· 8 people
- 26MOTS-cPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.6 reported0 people given it1 trial, 3 watch-only2 found nothing
found nothingThe gene variant that made MOTS-c famous for longevity turned out to do the opposite, and the longevity claim did not survive. Researchers pooled three large Japanese population studies covering 27,527 people. Nobody was given anything. Men carrying the weaker version of the MOTS-c gene had more type 2 diabetes, not less, and the pattern was strongest in men who did not exercise. In a separate group of 736 people aged 100 or more, the variant was no more common than in everyone else.
The numbers Meta-analysis of 27,527 people across three Japanese cohorts (J-MICC, MEC, TMM): the reduced-function C-allele of m.1382A>C was linked to higher, not lower, prevalence of type 2 diabetes in men, especially sedentary men. In an expanded cohort of 736 centenarians, allele frequency did not differ from controls (7.7% vs 7.5%), refuting the earlier longevity hypothesis.
Aging (Albany NY), 2021· 27,527 peopleobserved only, nobody was given it
This study points the other way, and the MOTS-c story does not hold together. A hundred and fifty-nine adults without diabetes or heart disease had their blood measured. Nobody was given anything. Those with metabolic syndrome carried more MOTS-c, not less, and levels rose with belly fat and with fat in the liver. That is the reverse of what the diabetes and heart studies found. When studies disagree this sharply, the honest reading is that nobody knows what a blood MOTS-c level means.
The numbers 125 Chinese adults plus 34 additional Caucasian women without overt type 2 diabetes or cardiovascular disease: plasma MOTS-c was higher, not lower, in those with metabolic syndrome and rose with android and liver fat, the opposite direction from studies in diabetes and coronary disease.
Biochimica et Biophysica Acta, General Subjects, 2021· 125 peopleobserved only, nobody was given it
found nothingHeavier boys carried less MOTS-c in their blood. Heavier girls did not. Forty obese children and teenagers in China were compared with fifty-seven of normal weight. Nobody was given anything. In boys, MOTS-c was about a fifth lower, at 465 against 584 units, and fell as weight, waist size, fasting insulin and average blood sugar rose. In girls there was no difference worth reporting. This is a snapshot of two groups, so it cannot tell you which came first.
The numbers 40 obese children/adolescents versus 57 controls in China: circulating MOTS-c was lower in obese boys (465 vs 584 ng/mL, p<.001) and correlated negatively with BMI, waist-to-hip ratio, fasting insulin, HOMA-IR and HbA1c; no significant difference in girls.
Pediatric Diabetes, 2018· 40 peopleobserved only, nobody was given it
Nobody has results yet. This is a trial that is still recruiting, not a finding. It plans to give 120 adults with extra weight and blood sugar creeping towards diabetes a daily injection of MOTS-c or a dummy for twelve weeks, alongside lifestyle advice. Neither the participants nor the staff will know who got which. The thing being measured is how well the body handles a sugar drink at the end. Recruitment began in February 2026 and the first results are expected in 2027.
The numbers Verified on ClinicalTrials.gov: two-arm, 1:1 randomized, quadruple-blind, placebo-controlled trial, estimated enrollment 120, daily subcutaneous injection for 12 weeks plus lifestyle counseling, primary outcome change in OGTT-derived insulin sensitivity (Matsuda Index) at week 12. Recruiting since February 2026; estimated primary completion February 2027.
ClinicalTrials.gov, Hudson Biotech, 2026· number of people not given
- 27AOD-9604PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.5 reported0 people given it1 trial1 found nothing
found nothingAOD9604 was tested properly for weight loss and it did not work. Six separate trials compared it with a dummy, and none of them delivered the fat loss the drug was built for. It did not change the growth hormone marker in the blood, and it did not change how people handled sugar. Its side effect profile looked the same as a dummy injection. So the honest summary is that it is safe and it is ineffective.
The numbers Summary of six randomized, double-blind, placebo-controlled human trials: AOD9604 (Tyr-hGH177-191) had no effect on IGF-1 or glucose tolerance and a safety profile indistinguishable from placebo; the programme did not establish efficacy for weight loss.
Journal of Endocrinology and Metabolism, 2013· number of people not given
Also measured in animals or in the lab
In obese rats, the fat-burning piece of growth hormone switched on a fat breakdown enzyme and slowed weight gain. It did not cause blood sugar problems.
The numbers The hGH 177-191 lipolytic domain stimulated hormone-sensitive lipase and reduced weight gain in obese rats without inducing insulin resistance or glucose intolerance.
Journal of Molecular Endocrinology, 2000· animal study
- 28ARA-290PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 5 completed trials, 95 people given it.7 reported0 people given it1 trial
People with diabetes and painful nerve damage injected ARA-290 daily for a month, and several measures moved. Average blood sugar and blood fats improved over two months of watching, and people reported less nerve pain. Nerve fibres in the eye increased only in those who started well below normal. The published summary never says how many people took part, which makes the result impossible to weigh. Nobody has repeated it.
The numbers 28 days of 4 mg per day self-administered subcutaneously in type 2 diabetes with painful neuropathy: improved HbA1c and lipids over 56 days of observation and improved PainDetect scores. Corneal nerve fiber density rose only in subjects starting more than 1 SD below normal. The abstract does not state the number randomized.
Molecular Medicine, 2015· number of people not given
- 29LixisenatidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 6,068 people given it.2 reported0 people given it1 trial
Added on top of insulin, the drug helped a little. People with type 2 diabetes whose insulin was not controlling them took lixisenatide or a dummy injection for six months. Their three month average blood sugar fell about 0.4 points further than the dummy group. The gain came mostly from lower blood sugar after meals. Nobody put on weight, which matters because insulin usually causes that. A 0.4 point move is a small effect, not a transforming one.
The numbers Placebo-corrected HbA1c reduction of 0.4% at 24 weeks with improved postprandial glucose and no weight gain.
Diabetes Care, 2013· number of people not given
- 30EcnoglutidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 664 people given it.1 reported0 people given it1 trial
This trial set the drug against dulaglutide, an established weekly injection, in people with type 2 diabetes already taking metformin. It ran for a year, and it was designed to show the newcomer was not worse rather than that it was better. That is a lower bar. It is also the right bar to set when a good treatment already exists.
The numbers 52-week Phase 3 non-inferiority trial versus dulaglutide in type 2 diabetes on metformin.
The Lancet Diabetes and Endocrinology, 2025· number of people not given
- 31KN069PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.0 people given it1 trial
The first human data look promising, and they come from a very small, very early study. Chinese men with overweight or obesity were given single rising doses, three on the drug for every one on a dummy, plus a smaller repeat-dose group. Side effects were mostly mild stomach and bowel complaints. The drug clears extremely slowly, staying in the body for weeks. At the best single dose, weight was down about 4.7% at day seven against 0.4% on the dummy.
The numbers First-in-human in Chinese men with overweight or obesity. Single ascending dose 12 to 120 mg, n = 36, randomised 3:1 active to placebo, plus multiple ascending dose n = 12 escalating 15 to 60 mg. Well tolerated with predominantly mild to moderate gastrointestinal adverse events. Dose-proportional exposure from 12 to 90 mg with a total-drug half-life of 899.74 to 1099.01 hours. Maximum early weight change at day 7 on 90 mg was minus 4.71% against minus 0.41% on placebo, sustained up to 133 days. In the multiple-dose part the 60 mg group reached minus 2.57% at day 25 with a significant fall in waist circumference (p = 0.0446). Fasting glucose, triglycerides and uric acid fell and insulin and C-peptide rose.
Diabetes, Obesity and Metabolism, 2026· number of people not given
- 32Neuropeptide YPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 20 people given it.5 reported0 people given it1 trial
This is a small mechanism study about diabetes drugs, not a test of neuropeptide Y as a treatment. Eighteen non smokers, twelve healthy and six with type 2 diabetes, took sitagliptin or a dummy pill in turn, and nobody involved knew which. Neuropeptide Y was then infused into an arm artery and blood flow was measured. It narrowed blood vessels, and it narrowed them more when sitagliptin was on board. The authors think this may explain some heart effects of that drug class in people on blood pressure medicines.
The numbers Eighteen non-smokers, twelve healthy controls and six with type 2 diabetes, in randomised double-blind placebo-controlled crossover studies of sitagliptin against placebo, with NPY infused into the brachial artery and forearm blood flow measured by plethysmography. NPY caused dose-dependent vasoconstriction, and sitagliptin significantly potentiated it during enalaprilat and during valsartan. The authors suggest this could contribute to the cardiovascular effects of DPP-4 inhibitors in patients taking an ACE inhibitor or an angiotensin receptor blocker. This is a mechanistic safety finding about diabetes drugs, not a therapeutic result for NPY.
Hypertension, 2018· number of people not given
- 33ApelinPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 68 people given it.3 reported0 people given it1 trial
This one finished and never said what it found. A hospital in Toulouse gave apelin or a dummy to 16 healthy volunteers and completed the study in October 2014. No results have been posted, and none had been as of September 2026. A companion study in 9 people with type 2 diabetes finished in April 2017 and is also silent. A completed trial that reports nothing is itself a finding, and not a reassuring one.
The numbers University Hospital Toulouse, phase 1, 16 healthy volunteers, apelin versus placebo, completed October 2014, no results posted as of 11 September 2026. A companion 9-person phase 1 in type 2 diabetes (NCT02724566) completed April 2017, also with no results posted. Completed and unreported is a finding.
ClinicalTrials.gov, 2014· number of people not given
- 34OsteocalcinPeptidePreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.nobody was given it1 watch-only study
The arrow points the other way. Osteocalcin was measured in 5,169 people in China, and lower levels went with higher blood sugar, insulin resistance, triglycerides, liver fat and weight. That is exactly what the bone hormone story predicts. Then the researchers used genetics to test which way the causation runs, and the genes say type 2 diabetes lowers osteocalcin rather than low osteocalcin causing diabetes. Nobody was given anything. This is the most important caveat on the page.
The numbers 5,169 Chinese participants with measured osteocalcin, plus bidirectional two-sample Mendelian randomisation against Biobank Japan and East Asian diabetes GWAS. Osteocalcin correlated with lower glucose, insulin resistance, triglycerides, liver fat and BMI, but the causal analysis supported type 2 diabetes lowering osteocalcin (causal effect -0.03, -0.05 to -0.01, p = 0.006 and p = 0.001 in two datasets), not the reverse.
Journal of Bone and Mineral Research, 2021· 5,169 peopleobserved only, nobody was given it
- 35BeinaglutidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 443 people given it.nobody was given it1 watch-only study
Nobody was given anything here. Researchers looked back at the records of 314 Chinese patients with type 2 diabetes. After three months, the records showed weight down 10.05 kg and average blood sugar down 2.87 points. Those numbers are far bigger than the careful study with a dummy-shot group found. Looking back only at people who stayed on a drug picks out the ones it suited. These figures should never be quoted as what the drug does.
The numbers Retrospective observational data on 314 Chinese patients with type 2 diabetes treated between 2017 and 2018. After three months, weight fell 10.05 kg and glycated haemoglobin 2.87 percentage points, with 84.96 percent losing at least 5 percent of body weight. These figures are far larger than the randomised phase 3 produced, which is what uncontrolled retrospective selection does to effect estimates, and they should not be quoted as the drug's effect size.
Obesity Science and Practice, 2019· 314 peopleobserved only, nobody was given it
Also measured in animals or in the lab
In mice made obese on a fatty diet. Treated mice had lower weight, less fat and lower blood fats. Their fat tissue responded better to insulin. The kinds of fat stored in that tissue changed, and so did the genes that handle fat. None of this has been measured in a human study of this drug.
The numbers Diet-induced obese mice. Treated animals showed lower body weight, fat mass and plasma lipids, improved insulin sensitivity in white adipose tissue, and changes in the content and composition of glycerolipids, glycerophospholipids and sphingolipids alongside altered expression of lipid metabolism genes. A mouse mechanism study; none of these lipidomic endpoints has been measured in a human trial of this drug.
iScience, 2021· animal study
- 36PancragenPeptidePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.nobody was given it1 watch-only study1 found nothing
found nothingBlood sugar markers improved, and there was no proper comparison group. 33 people with type 2 diabetes and 30 healthy older adults took pancragen. In the diabetes group, fasting blood sugar, a sugar drink test, insulin and a measure of insulin resistance all came down. Untreated patients did not change. The study is small, and it comes from the same single research group as everything else written about pancragen.
The numbers 30 healthy older adults and 33 with type 2 diabetes. In the diabetes group pancragen lowered fasting glucose, glucose on a standard tolerance test, plasma insulin and an insulin-resistance index, while untreated patients did not change. Small, uncontrolled, and from the same single research lineage as the rest of the pancragen literature.
Bulletin of Experimental Biology and Medicine, 2011· 30 peopleobserved only, nobody was given it
Also measured in animals or in the lab
In old female monkeys. Ten days of the peptide sped up how fast they cleared sugar from the blood and brought their insulin response back to normal. Part of the effect was still there three weeks after stopping. Same research group.
The numbers 50 micrograms per animal per day for 10 days in old female rhesus monkeys raised the glucose disappearance rate and normalised insulin and C-peptide responses, with a partial effect still present three weeks after stopping. Same research lineage.
Advances in Gerontology (Uspekhi Gerontologii), 2014· animal study
- 37HumaninPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.6 reportednobody was given it1 watch-only study
People whose fasting blood sugar had started to drift up carried less humanin. Twenty-three of them were compared with fifty-eight people whose blood sugar was normal, at a clinic screening for diabetes complications. Nobody was given anything. Humanin in the blood was about two fifths lower in the higher sugar group, at 124.3 against 204.8 units. The authors think the body's protective response has weakened. Twenty-three people is a very small group, and one measurement cannot show what caused what.
The numbers Diabetes complications screening clinic: plasma humanin was significantly lower in 23 people with impaired fasting glucose than in 58 controls (124.3 vs 204.8 pg/mL, p=.0001), interpreted by the authors as a blunted adaptive response.
Physiological Reports, 2016· 23 peopleobserved only, nobody was given it
Also measured in animals or in the lab
In rats, humanin given to the brain or the body made the whole body respond better to insulin, through a signal in the brain. Humanin levels fell with age in rodents. In a group of people it also fell with age, but the paper does not say how many people.
The numbers Central or peripheral humanin improved whole-body insulin sensitivity in rats via hypothalamic STAT-3; humanin levels fell with age in rodents and, in a cross-sectional human sample, in humans (exact cohort size not reported in the published methods).
PLoS One, 2009· animal study
- 38UBT251PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.1 reportednobody was given it1 watch-only study
Blood sugar fell as well as weight in people with type 2 diabetes. Average blood sugar over about three months dropped by up to 2.16 percentage points after 24 weeks, which is a large fall for a diabetes drug. This came from a company announcement about a mid-stage Chinese trial. No independent reviewer has seen the full data, and everyone in the study was Chinese.
The numbers Glycemic benefit alongside weight loss.
Novo Nordisk press release, 2026· number of people not givenobserved only, nobody was given it
- 39GIPPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 10 people given it.2 reportednobody was given it1 watch-only study
GIP slows the breakdown of bone, and it does not need insulin or blood sugar to do it. Blood markers of bone breakdown dropped on the hormone compared with a control. The effect held when insulin and blood sugar were taken into account. This is the most repeated human effect of GIP outside blood sugar. It was measured in blood over hours. Nobody checked whether bones got stronger or broke less.
The numbers Randomised. GIP acutely suppresses bone resorption, and does so independently of insulin and blood glucose. This is the best-replicated non-glycaemic human effect of GIP.
Journal of Clinical Endocrinology and Metabolism, 2018· number of people not givenobserved only, nobody was given it
Supplements
11 compounds · 814 people given one of themVitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.
- 01ResveratrolSupplementModerate. At least one finished study in people, and at least 100 people who took it. 14 completed trials, 403 people given it.7 reported357 people given it8 trials7 found nothing
found nothingThe longest and largest diabetes trial of resveratrol found nothing that counted. 192 patients took 40 mg, 500 mg or a dummy pill every day for six months. An inflammation marker fell further on resveratrol, but not by enough to call real. Weight, waist, blood pressure, blood sugar, insulin and a string of other markers did not change. Cholesterol and triglycerides rose slightly on the high dose. Patients earlier in their diabetes did show a real fall in inflammation.
The numbers The largest and longest diabetes trial here: 192 patients, 40 or 500 mg per day for six months. CRP fell 5.6% and 15.9% versus placebo but not significantly, and there was no significant change in weight, BMI, waist, blood pressure, fasting glucose, HbA1c, insulin, C-peptide, free fatty acids, liver enzymes, uric acid, adiponectin or IL-6. Total cholesterol and triglycerides rose slightly on 500 mg. Subgroups with shorter diabetes duration did show a significant CRP reduction.
Pharmacological Research, 2016· 192 people
found nothingThe longest resveratrol trial found a small gain in thinking that has not been confirmed since. 125 women past menopause, aged 45 to 85, took 75 mg twice a day for a year and a dummy pill for another year. Their overall thinking scores came out better on resveratrol, though the gain was small. Blood flow in the brain, fasting insulin and insulin resistance improved too. A 2025 review pooling ten trials in 928 women found no effect on thinking or memory.
The numbers The longest resveratrol trial published: 125 postmenopausal women aged 45 to 85, 75 mg twice daily for 12 months then crossover for 12 months. Overall cognitive performance improved 33% versus placebo, though the effect size was small (Cohen's d = 0.170, p = 0.005). Resting cerebral blood flow velocity (d = 0.275, p = 0.001), fasting insulin and insulin resistance index also improved. A 2025 meta-analysis of 10 trials in 928 postmenopausal women found no significant effect on cognition or memory, so this result is not settled.
Clinical Nutrition, 2021· 125 people
found nothingA tiny dose improved insulin resistance in nineteen patients over four weeks. A marker of oxidative damage in the urine fell, and a signalling protein in the blood platelets rose. The insulin-making cells did not change. The odd thing here is the dose. It is a hundredth of what most good trials use, which is hard to square with the idea that more does more.
The numbers Nineteen patients, double-blind, 2 x 5 mg per day for four weeks. HOMA-IR and urinary ortho-tyrosine fell and the platelet pAkt:Akt ratio rose; beta-cell function (HOMA-B) did not change. Notable because the dose is a hundredth of what most positive trials use, which cuts against a simple dose-response story.
British Journal of Nutrition, 2011· 19 people
This is the strongest good human result resveratrol has, and it rests on eleven men. Obese but otherwise healthy men took 150 mg a day for a month, and also spent a month on a dummy pill. Their resting metabolism slowed the way it does when people eat less. Liver fat, blood sugar, triglycerides, a liver enzyme and inflammation markers all fell. Blood pressure improved. Muscle samples showed the cell's energy machinery switched on.
The numbers Eleven healthy obese men, randomised double-blind crossover, 150 mg per day for 30 days. Sleeping and resting metabolic rate fell; muscle AMPK was activated with higher SIRT1 and PGC-1alpha protein and improved mitochondrial respiration on a fatty-acid substrate; intrahepatic lipid, circulating glucose, triglycerides, ALT and inflammation markers fell; systolic blood pressure and HOMA improved. The strongest positive mechanistic human result in the literature, in eleven men.
Cell Metabolism, 2011· 11 people
Also measured in animals or in the lab
found nothingIn a dish. The main challenge, from Pfizer. With natural test proteins that had no glowing tag, none of the four compounds switched SIRT1 on. They only worked with the tagged test protein, because they stick to the tag. One of them also failed to lower blood sugar in mice on a fatty diet.
The numbers The central challenge, from Pfizer. Using a p53-derived peptide with no fluorophore, and full-length native p53 and acetyl-CoA synthetase 1, none of the four compounds activated SIRT1; they activated it only with the fluorophore-tagged peptide. NMR, surface plasmon resonance and calorimetry showed the compounds bind the labelled peptide itself. SRT1720 also failed to lower plasma glucose in high-fat-fed mice. Amgen (Beher, 2009) had reported the same fluorophore artefact a year earlier, and Kaeberlein and colleagues first raised it in 2005.
Journal of Biological Chemistry, 2010· lab (cells in a dish)
- 02BerberineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 186 people given it.4 reported186 people given it3 trials
A larger diabetes study than the famous 36 person one. 116 adults with type 2 diabetes and high blood fats took 1 gram of berberine a day, or a dummy pill, for three months. Fasting sugar fell from 7.0 to 5.6. HbA1c fell from 7.5 to 6.6 percent. Triglycerides, total cholesterol and LDL fell too. It measured blood tests, not heart attacks or deaths.
The numbers 116 adults with type 2 diabetes and dyslipidaemia randomised to berberine 1.0 g/day or placebo for 3 months. Fasting glucose 7.0 to 5.6 mmol/L, post-load 12.0 to 8.9, HbA1c 7.5% to 6.6%, triglycerides 2.51 to 1.61, LDL 3.23 to 2.55, all versus placebo p <= 0.001.
Journal of Clinical Endocrinology and Metabolism, 2008· 116 people
Berberine lowered blood sugar about as well as metformin in a very small, short study. Thirty-six adults newly diagnosed with type 2 diabetes took either berberine or metformin three times a day for three months. Average blood sugar over three months fell from 9.5 to 7.5 percent on berberine. A second group of 48 poorly controlled patients added berberine and fell from 8.1 to 7.3 percent. About a third had stomach upset that passed. Thirty-six people cannot settle a question about a lifelong disease.
The numbers The head to head everyone cites. 36 adults with newly diagnosed type 2 diabetes randomised to berberine or metformin 0.5 g three times daily for three months, with the hypoglycaemic effect similar between them. HbA1c fell from 9.5% to 7.5% on berberine. A second arm added berberine in 48 poorly controlled patients, with HbA1c falling from 8.1% to 7.3%. 34.5% of patients had transient gastrointestinal adverse effects.
Metabolism, 2008· 36 people
A small prediabetes pilot moved the same sugar numbers. 34 people took a branded berberine, or a dummy, for 12 weeks. Fasting sugar fell from 6.75 to 5.33. The two hour sugar test fell too. 34 people is a pilot. A branded product result does not transfer to every bottle on the shelf.
The numbers 34 adults with prediabetes randomised to HIMABERB berberine or placebo for 12 weeks. Fasting glucose 6.75 to 5.33 mmol/L, two-hour OGTT 10.44 to 8.12, with parallel falls in fasting insulin and HbA1c versus control.
BMC Endocrine Disorders, 2023· 34 people
- 03NMNSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 94 people given it.6 reported80 people given it3 trials3 found nothing
found nothingNMN raised NAD in the blood and added a little to how far people could walk, and did nothing for blood sugar handling. Eighty healthy middle aged adults took one of three daily doses or a dummy for two months, and nobody involved knew which. Walking distance in six minutes improved modestly. Insulin resistance did not budge. Most people took it without trouble. Two months is short, walking distance is easy to improve, and nobody was followed long enough to see whether anything lasted.
The numbers 60-day RCT in 80 adults: 300 to 900 mg/day raised blood NAD and modestly improved six-minute walk distance; well tolerated; HOMA-IR unchanged.
GeroScience, 2023· 80 people
found nothingNMN improved one thing in one narrow group of people, and left everything else alone. The women taking part were past menopause, carried extra weight and had blood sugar creeping towards diabetes. Half took NMN daily for ten weeks, half took a dummy pill, and nobody involved knew which. Muscle became more responsive to insulin in the NMN group. Nothing else the researchers measured changed. This was a small study in one kind of person, so it says nothing about men, or about anyone healthy.
The numbers 10-week RCT in overweight or obese postmenopausal women with prediabetes: 250 mg/day NMN increased muscle insulin sensitivity and insulin signaling versus placebo; other metabolic outcomes did not change.
Science, 2021· number of people not given
found nothingA high dose NMN tablet raised NAD in the blood and moved weight and cholesterol, but not muscle. 30 overweight or obese adults took MIB-626, 1000 mg twice a day, or a dummy pill, for 28 days. Weight fell 1.9 kg. The lower blood pressure number and LDL cholesterol fell too. Strength, tiredness, fitness and stair climbing power did not change. Neither did the body's response to insulin. The maker paid for it.
The numbers 30 overweight or obese adults aged 45 and over randomised 2:1 to MIB-626 (microcrystalline NMN) 1000 mg twice daily or placebo for 28 days. Weight -1.9 kg, diastolic BP -7.01 mmHg, LDL -18.73 mg/dL versus placebo. Muscle strength, fatigability, aerobic capacity and stair-climbing power did not differ. Insulin sensitivity unchanged. Funder: Metro International Biotech.
Journal of Clinical Endocrinology and Metabolism, 2023· number of people not given
Also measured in animals or in the lab
In mice, 12 months of NMN by mouth improved how they handled sugar, used energy, moved around and saw, with no obvious harm.
The numbers 12 months of oral NMN in ageing mice improved insulin sensitivity, energy metabolism, physical activity and eye function without obvious toxicity.
Cell Metabolism, 2016· animal study
- 04SulforaphaneSupplementModerate. At least one finished study in people, and at least 100 people who took it. 7 completed trials, 423 people given it.6 reported74 people given it2 trials
It missed the target the researchers set in advance, and the effect it did produce was smaller. 74 adults with prediabetes who were on no diabetes drugs took broccoli sprout extract or a dummy for 12 weeks, 35 and 39 of them. They had said beforehand they needed fasting blood sugar to drop by 0.3 units to count. It dropped 0.2. Stomach side effects occurred and nothing severe happened. A group of apparent responders was picked out afterwards, which raises a question rather than answering one.
The numbers 74 drug-naive adults with prediabetes randomised to broccoli sprout extract (n = 35) or placebo (n = 39) for 12 weeks. The authors report that the extract did not meet the prespecified primary outcome of a 0.3 mmol/L fall in fasting blood glucose; the overall effect was 0.2 mmol/L (95 percent CI -0.44 to -0.01, p = 0.04). Gastrointestinal side effects, no severe adverse events. A responder subgroup was identified in exploratory analysis, which is hypothesis generating rather than confirmatory.
Nature Microbiology, 2025· 74 people
The human part of this much-cited paper is the smallest part of it. Sulforaphane was picked out by computer, by matching a diabetic liver pattern against 3,800 drug patterns. It cut sugar production in liver cells. In diabetic animals it improved glucose handling about as much as metformin. Finally, in a small human group, obese patients with poorly controlled type 2 diabetes took concentrated sprout extract and their fasting and average blood sugar came down. A later prediabetes trial could not confirm that human piece.
The numbers A multi-part paper. Sulforaphane was identified computationally by matching a type 2 diabetes liver disease signature against 3,800 drug signatures; it suppressed glucose production in hepatic cells via NRF2 nuclear translocation, attenuated glucose intolerance in diabetic animals by a magnitude similar to metformin, and in the final human component, given as concentrated broccoli sprout extract, reduced fasting blood glucose and HbA1c in obese patients with dysregulated type 2 diabetes. The human arm is the smallest part of the paper and is the part that the later prediabetes trial did not confirm on its primary endpoint.
Science Translational Medicine, 2017· number of people not given
- 05EpicatechinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 44 people given it.1 reported37 people given it2 trials2 found nothing
found nothingPure epicatechin did not improve blood vessel function, and the small insulin change is easy to over-read. 37 adults aged 40 to 80 with raised blood pressure took 100 mg a day for four weeks, and each also took a dummy for four weeks, in turn. Artery widening improved slightly, too little to separate from chance. Fasting insulin fell a little. Blood pressure, artery stiffness and cholesterol did not budge. No funding was stated in the abstract retrieved.
The numbers 37 adults aged 40 to 80 with systolic pressure 125 to 160 mmHg, 100 mg (-)-epicatechin a day for 4 weeks in crossover. Flow-mediated dilation: +1.1 percentage points, 95 percent CI -0.1 to 2.3, p = 0.07, not significant. Fasting insulin fell 1.46 mU/L (p = 0.03) and HOMA-IR fell 0.38 (p = 0.04). No change in blood pressure, arterial stiffness or lipids. Funding not stated in the abstract retrieved.
American Journal of Clinical Nutrition, 2015· 37 people
found nothingA food-sized dose of pure epicatechin did nothing. 48 overweight or obese non-smokers with features of metabolic syndrome took 25 mg a day for two weeks, and each took a dummy for two weeks as well, in turn. Nothing moved: not blood pressure, glucose, insulin, triglycerides, or any cholesterol measure. The authors conclude that whatever cocoa does, epicatechin alone does not explain it. Two weeks is short, and the dose was deliberately a dietary one.
The numbers 48 overweight or obese non-smokers aged 20 to 65 with features of metabolic syndrome, 25 mg (-)-epicatechin a day for 2 weeks in crossover. No significant effect on blood pressure, glucose, insulin, HOMA-IR, triglycerides, total, LDL or HDL cholesterol, or oxidised LDL. The authors conclude the cocoa effect cannot be ascribed to epicatechin alone.
American Journal of Clinical Nutrition, 2018· number of people not given
- 06L-leucineSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.3 reported30 people given it1 trial1 found nothing
found nothingThree months of leucine did nothing at all for muscle in healthy older men. 30 men averaging 71 took 2.5 g of leucine with each main meal, 7.5 g a day, or a dummy, decided by chance. Scans of muscle size showed no change in either group. Strength on a one-lift maximum did not change either. Insulin sensitivity, long-run blood sugar and blood fats were all unmoved. These men were healthy to begin with, not frail and not already losing muscle.
The numbers 30 healthy men, mean age 71, randomised to 2.5 g leucine or placebo with each main meal, 7.5 g daily for three months. No change in skeletal muscle mass measured by computed tomography and DXA, and no change in one-repetition-maximum strength, in either group. No improvement in whole-body insulin sensitivity, HbA1c or plasma lipids.
American Journal of Clinical Nutrition, 2009· 30 people
- 07OxaloacetateSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 112 people given it.4 reported30 people given it1 trial1 found nothing
found nothingIt was safe and it reached the brain, but thinking did not get better. 30 people with Alzheimer's disease, 15 in each group, took 500 or 1,000 mg twice a day for one month. Both doses were tolerated. The higher dose raised how much sugar the brain took up in several regions and lifted an antioxidant in two of them. Blood levels moved inconsistently. Cognitive scores did not improve. One month in 30 people tests safety and biology, not whether anyone benefits.
The numbers 30 participants with Alzheimer's disease, 15 per group, given 500 or 1,000 mg twice daily for one month. Both doses were safe and tolerated. The higher dose increased FDG PET glucose uptake across multiple brain regions and raised parietal and frontoparietal glutathione. Blood level changes were not consistent, and cognitive scores did not improve.
Alzheimer's and Dementia, 2021· 30 people
- 08TUDCASupplementLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 54 people given it.7 reported20 people given it1 trial1 found nothing
found nothingFour weeks of TUDCA improved insulin sensitivity in liver and muscle, and not in fat. 20 obese adults took 1,750 mg a day or a dummy for four weeks, with detailed infusion tests and samples from muscle and fat. Liver and muscle insulin sensitivity rose by roughly 30 percent while the dummy group did not change. The cell stress markers that were meant to explain all this did not move in either tissue. NIH funded. Twenty people over four weeks is a mechanism study.
The numbers 20 obese adults, mean age 48 and BMI 37, randomised to 1,750 mg a day of TUDCA or placebo for 4 weeks, with two-stage hyperinsulinaemic-euglycaemic clamps, tracer infusions and muscle and adipose biopsies. Hepatic and muscle insulin sensitivity rose approximately 30 percent (p < 0.05) with no change on placebo, and muscle insulin signalling improved. Markers of endoplasmic reticulum stress in muscle and adipose tissue did not change after either treatment, despite that being the hypothesised mechanism. NIH funded.
Diabetes, 2010· 20 people
- 09Nicotinamide RibosideSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 90 people given it.5 reported0 people given it1 trial1 found nothing
found nothingIn obese men, it did not help. 40 inactive men with a BMI over 30 took 1000 mg twice a day, or a dummy pill, for 12 weeks. A careful test of how their bodies handled insulin showed no change. Neither did how they burned fuel, their body fat or muscle, or the fat in their liver. It was safe. Raising NAD in a mouse and fixing insulin in a man turned out to be different things.
The numbers 40 obese insulin-resistant sedentary men, BMI over 30, aged 40 to 70, randomised to NR 1000 mg twice daily or placebo for 12 weeks. Insulin sensitivity by hyperinsulinaemic euglycaemic clamp, endogenous glucose production, glucose disposal, resting energy expenditure, lipolysis and body composition did not improve. Safe. NCT02303483.
American Journal of Clinical Nutrition, 2018· number of people not given
- 10MIB-626SupplementModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 107 people given it.1 reported0 people given it1 trial1 found nothing
found nothingThe tablet moved some body measurements and left every measure of physical function untouched. 30 overweight or obese adults aged 45 and over took MIB-626 or a dummy tablet for four weeks. Weight fell by about two kilograms. Blood pressure and cholesterol both came down. Strength, stamina, how quickly muscles tired and stair climbing power did not change. Insulin sensitivity, liver fat and belly fat did not change either. The manufacturer helped fund it. This study looked at many things at once, so treat any single result as a hint.
The numbers Randomised 2:1, 30 overweight or obese adults aged 45 and over, MIB-626 two 500 mg tablets twice daily for 28 days. Body weight fell 1.9 kg (95 percent CI -3.3 to -0.5, P=.008), diastolic blood pressure fell 7.01 mmHg (-13.44 to -0.59, P=.034), total cholesterol fell 26.89 mg/dL (P=.004) and LDL fell 18.73 mg/dL (P=.007). Muscle strength, muscle fatigability, aerobic capacity and stair-climbing power did not change. Insulin sensitivity, hepatic fat and intra-abdominal fat did not change in either group. Metro International Biotech, the manufacturer, is a listed funder. This is a physiologic study with multiple outcomes rather than a trial powered on one of them.
Journal of Clinical Endocrinology and Metabolism, 2023· number of people not given
- 11Alpha-ketobutyrateSupplementPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.3 reportednobody was given it2 watch-only studies
Two long follow-up studies say the same thing, and it is not a longevity finding. 1,261 people without diabetes were followed for three years and 2,580 more for 9.5 years. Nobody was given anything; researchers watched and measured. Higher alpha-hydroxybutyrate went with more insulin resistance and predicted who would go on to develop high blood sugar or type 2 diabetes. That held after accounting for family history, sex, age, body size and fasting glucose. In pancreas cells in a dish, the same chemical blocked insulin release.
The numbers 1,261 non-diabetic participants in the RISC study followed 3 years and 2,580 in the Botnia Prospective Study followed 9.5 years. Alpha-hydroxybutyrate was a positive correlate of insulin resistance and an independent predictor of incident dysglycaemia or type 2 diabetes, adjusted odds ratios 1.25 (95 percent CI 1.00 to 1.60) and 1.26 (1.07 to 1.48) per standard deviation, independent of familial diabetes, sex, age, BMI and fasting glucose. In INS-1e cells alpha-hydroxybutyrate inhibited glucose-induced insulin release.
Diabetes, 2013· 1,261 peopleobserved only, nobody was given it
In people, this chemical marks metabolic trouble rather than health. Researchers screened the blood chemistry of people without diabetes and found alpha-hydroxybutyrate, which the body makes from alpha-ketobutyrate, rising early in insulin resistance and poor glucose handling. Nobody was given anything here. This is the human setting the lifespan claim has to sit inside. In humans, this branch of metabolism runs high in the people heading toward metabolic disease, not in the ones staying well.
The numbers The metabolomic screen that identified alpha-hydroxybutyrate, the reduction product of alpha-ketobutyrate, as an early marker of insulin resistance and glucose intolerance in non-diabetic people. This is the human context that the lifespan claim sits inside: in people, this branch of metabolism is elevated in the direction of metabolic disease rather than health.
PLoS One, 2010· number of people not givenobserved only, nobody was given it
Other compounds
22 compounds · 12,363 people given one of themApproved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.
- 01EmpagliflozinSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 16,738 people given it.4 reported7,020 people given it1 trial1 found nothing
found nothingA diabetes drug that turned out to keep people alive. 7,020 people with type 2 diabetes and high heart risk took empagliflozin or a dummy for about three years. 12.1 percent of the dummy group had a heart attack, had a stroke, or died of heart disease. On empagliflozin, 10.5 percent did. Deaths from any cause were 8.3 percent against 5.7 percent. Heart attacks and strokes alone did not change, so the gain came from fewer deaths. Genital infections were more common on the drug.
The numbers EMPA-REG OUTCOME. 7,020 people with type 2 diabetes at high cardiovascular risk, median observation 3.1 years. The primary composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke occurred in 10.5 percent on empagliflozin against 12.1 percent on placebo (hazard ratio 0.86, P = 0.04). Death from any cause was 5.7 percent against 8.3 percent, a 32 percent relative risk reduction. There was no significant difference in rates of myocardial infarction or stroke, and genital infection was more common on the drug.
New England Journal of Medicine, 2015· 7,020 people
- 02OrforglipronSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 8 completed trials, 17,383 people given it.8 reported2,660 people given it3 trials, 1 watch-only
Head to head against the rival pill, it controlled blood sugar better and was harder to put up with. 1,698 adults on metformin took orforglipron or oral semaglutide for a year. Average blood sugar fell further on orforglipron at both dose pairings. Tolerability went the other way every time. Roughly six in ten had stomach and bowel side effects, against four to five in ten. About twice as many quit over side effects, and resting pulse rose more. Everyone knew which drug they were taking. Eli Lilly funded it.
The numbers 1,698 adults on metformin, 52 weeks, head to head against oral semaglutide. From a baseline HbA1c of 8.3 percent, orforglipron 12 mg gave -1.71 and 36 mg -1.91 against semaglutide 7 mg -1.23 and 14 mg -1.47, meeting non-inferiority and then superiority at both pairings. Orforglipron was worse on tolerability at every comparison: gastrointestinal events 58 to 59 percent against 37 to 45 percent, discontinuation for adverse events 9 to 10 percent against 4 to 5 percent, pulse rise 3.7 and 4.7 bpm against 1.0 and 1.5. Open label, funded by Eli Lilly.
The Lancet, 2026· 1,698 people
A pill in this drug class produced real weight loss in people with both obesity and type 2 diabetes. 1,613 adults took one of three doses or a dummy pill for about seventeen months. Weight fell by roughly 5, 7 and 10 percent as the dose rose, against about 2 percent on the dummy. More people quit for side effects on the drug. Ten people died, six on drug and four on dummy, judged unrelated. Eli Lilly funded it, and some authors are employees who hold its stock.
The numbers 1,613 adults with obesity and type 2 diabetes across 136 sites in ten countries, 72 weeks. Weight change by the treatment-regimen estimand was -5.1, -7.0 and -9.6 percent on 6, 12 and 36 mg against -2.5 percent on placebo, all p<0.0001. Discontinuation for adverse events 6.1 to 9.9 percent against 4.1 percent. Ten deaths, six on drug and four on placebo, all judged unrelated except one placebo case and one 12 mg case for which no treatment-related association was reported. Funded by Eli Lilly, with employee-shareholder authors.
The Lancet, 2026· 1,613 peopleobserved only, nobody was given it
It beat the rival pill on blood sugar and lost to it on side effects. 962 adults on metformin were sorted by chance to orforglipron or dapagliflozin for about ten months. Average blood sugar fell further on orforglipron at every dose. Stomach and bowel trouble was the price: roughly half that group had it, against one in eight on dapagliflozin. Around three times as many stopped their tablets. Nobody had a dangerous blood sugar low. Everyone knew which drug they were on. Eli Lilly paid for the trial.
The numbers 962 adults on metformin, 40 weeks, open label with the orforglipron dose blinded. HbA1c fell 1.23, 1.50 and 1.56 percentage points on 3, 12 and 36 mg against 0.81 on dapagliflozin 10 mg, all treatment differences p<0.0001. Tolerability ran the other way: gastrointestinal events in 46 to 54 percent against 12 percent, and study drug discontinuation in 15 to 20 percent against 6 percent. No severe hypoglycaemia. Funded by Eli Lilly.
The Lancet, 2026· 962 people
In people early in type 2 diabetes, the tablet pulled average blood sugar down hard. Adults took orforglipron or a dummy tablet for about nine months. Their three month average blood sugar fell by 1.24 to 1.48 points, depending on the dose. On the dummy it fell 0.41 points. That is a large move for a diabetes drug you swallow. These people were early in the disease, so this does not say what happens after years of it.
The numbers Phase 3: HbA1c fell 1.24 to 1.48 points at 40 weeks versus 0.41 with placebo.
New England Journal of Medicine, 2025· number of people not given
- 03AlbiglutideBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 10,304 people given it.841 people given it2 trials
In a head to head against liraglutide, albiglutide lost. 841 adults were split by chance between the two drugs for eight months, and everybody knew which they were on. Average blood sugar fell further on liraglutide. Albiglutide was meant to prove it was no worse, and it failed to prove that. Injection site reactions were more than twice as common on albiglutide. Stomach side effects were less common. GlaxoSmithKline funded it, and the result still went against their drug.
The numbers 841 adults randomised to albiglutide 30 mg weekly (titrated to 50 mg) or liraglutide titrated to 1.8 mg daily, 32 weeks, open-label. HbA1c change minus 0.78 percentage points against minus 0.99; difference 0.21 (95 percent CI 0.08 to 0.34), non-inferiority not met at the 0.3 margin (P equals 0.0846). Injection site reactions 12.9 against 5.4 percent; gastrointestinal events 35.9 against 49.0 percent. Funded by GlaxoSmithKline. A head to head result in which the comparator won on the primary endpoint.
Lancet Diabetes and Endocrinology, 2014· 841 people
Albiglutide let most people drop their mealtime insulin without losing blood sugar control. 814 people on insulin were split by chance: one group swapped mealtime insulin for albiglutide, the other carried on. After six months blood sugar was the same in both. More than half on albiglutide stopped mealtime insulin entirely. They lost two kilograms while the others gained two and a half. Stomach side effects were twice as common. Published after the drug had already been withdrawn. The sponsor paid.
The numbers 814 people on basal plus prandial insulin randomised to albiglutide plus glargine with lispro withdrawn (402) or continued lispro plus glargine (412), 26 weeks. HbA1c 6.7 against 6.6 percent, non-inferior; 54 percent on albiglutide stopped all prandial insulin; weight minus 2.0 against plus 2.4 kg; documented hypoglycaemia 57.2 against 75.0 percent; gastrointestinal adverse events 26 against 13 percent. Published after the drug was withdrawn. Sponsor funded.
Diabetes Care, 2020· number of people not given
- 04DulaglutideBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 10,500 people given it.1 reported599 people given it1 trial
A weekly shot matched a daily one for blood sugar control. 599 people with type 2 diabetes already on metformin took either weekly dulaglutide or daily liraglutide for six months. Average blood sugar over three months fell by about the same amount on each. The trial was built only to show the weekly drug was no worse, never that it was better. Everybody knew which drug they were on. Nobody got a dummy shot, so neither result can be compared against no treatment at all.
The numbers 599 patients: weekly dulaglutide 1.5 mg was noninferior to daily liraglutide 1.8 mg for HbA1c reduction at 26 weeks.
The Lancet, 2014· 599 people
- 05MetforminSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 489 people given it.6 reported395 people given it2 trials, 2 watch-only
The longest follow-up in people we have found no drop in deaths. 3234 adults at high risk of diabetes were given metformin, an intensive lifestyle program, or a dummy pill. After a median 21 years, 453 had died. Neither metformin nor lifestyle cut deaths from any cause, cancer or heart disease. Preventing diabetes and preventing death were different questions, and only the first one moved.
The numbers DPP and DPPOS. 3,234 adults at high risk for type 2 diabetes, median 21 years. 453 deaths. Neither metformin nor lifestyle reduced all-cause, cancer or cardiovascular mortality.
Diabetes Care, 2021· 3,234 peopleobserved only, nobody was given it
This is the diabetes study that made metformin a first-choice drug, not a longevity study. 342 overweight adults with new type 2 diabetes took metformin, and 411 stayed on diet as the main plan. They were followed for a median of 10.7 years. Deaths from any cause were 36 percent lower on metformin. A second part of the paper added metformin to the top dose of a sulphonylurea pill, and it pointed the other way on diabetes deaths. Nobody here was a healthy adult taking it to age slower.
The numbers UKPDS 34. 342 overweight adults with newly diagnosed type 2 diabetes randomised to metformin versus 411 on conventional diet policy, median 10.7 years. All-cause mortality risk reduction 36% (95% CI 9 to 55). A supplementary randomisation adding metformin to maximum sulphonylurea found a higher risk of diabetes-related death. Not a trial in people without diabetes.
Lancet, 1998· 342 peoplepoints the wrong way
Metformin dulled the gains from exercise again, this time from cardio. 53 adults with an average age of 62 did 12 weeks of aerobic training, on either metformin or a dummy pill. The people on metformin improved less in fitness, and less in how well their bodies handled blood sugar. Training still helped them. It just helped them less than it helped everyone else.
The numbers 53 adults averaging 62 years did 12 weeks of aerobic training on metformin or placebo, double-blinded. Metformin diminished the training-induced improvements in insulin sensitivity and cardiorespiratory fitness.
Aging Cell, 2019· 53 people
Twenty years of Welsh records tell the same story. 129140 people on metformin for type 2 diabetes did not outlive matched people without diabetes. An early bump in the first three years reversed after five. A short window can manufacture a longevity claim that a long window erases.
The numbers Welsh SAIL records. 129,140 metformin-treated type 2 diabetes patients versus matched non-diabetic controls. Over a twenty-year window metformin patients had shorter survival than controls. An apparent benefit in the first three years reversed after five.
BMC Public Health, 2023· number of people not givenobserved only, nobody was given it
- 06MitoglitazoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 385 people given it.1 reported356 people given it1 trial, 1 watch-only
It lowered blood sugar about as well as the older drug it was meant to improve on, with less water retention. 356 people with type 2 diabetes were split by chance between three doses of mitoglitazone, pioglitazone, or a dummy pill, for twelve weeks, and 258 finished. Fasting blood sugar fell about the same on both real drugs. The blood changes that signal water retention were about half the size. Metabolic Solutions Development Company paid for it.
The numbers Phase 2b, 12 weeks, 258 completers of 356 randomised to 50, 100 or 150 mg mitoglitazone, pioglitazone 45 mg or placebo. Fasting glucose fell equally on the two active drugs; HbA1c reductions at 100 and 150 mg were not different from pioglitazone; haematocrit, red cell and haemoglobin changes indicating fluid retention were 50 percent smaller; HMW adiponectin rose less (p < 0.0001). Sponsored by Metabolic Solutions Development Company.
Clinical Pharmacology and Therapeutics, 2013· 356 people
This is the registry entry for the diabetes trial above. 356 people enrolled, it finished in December 2011, and results were posted in March 2013. The main thing it was built to measure was the change in fasting blood sugar at twelve weeks. The published paper describes what came of it. The company behind the drug, Metabolic Solutions Development Company, ran it.
The numbers Registry record: 356 enrolled, completed December 2011, results posted March 2013, sponsor Metabolic Solutions Development Company. Primary endpoint change in fasting plasma glucose at week 12.
ClinicalTrials.gov, 2013· 356 peopleobserved only, nobody was given it
- 07DHEAHormoneModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 267 people given it.5 reported144 people given it1 trial1 found nothing
found nothingThe biggest study of DHEA against a dummy pill as an anti-ageing supplement found nothing that mattered. 144 older men and women with low levels took it for two years. The hormone went up and little else changed. Body shape, strength, fitness, blood sugar control and quality of life did not get better. Bone density went up slightly at one spot in men and one in women. These were healthy volunteers with low levels, not patients.
The numbers 144 people, 87 men and 57 women aged 60 or over with low DHEA-S, randomised double-blind to 2 years of oral DHEA, testosterone (men only) or placebo. DHEA raised serum DHEA-S by a median 3.4 mcg/mL in men and 3.8 in women. No significant effect on body composition, peak oxygen uptake, muscle strength, insulin sensitivity or quality of life. Small gains in bone density at the femoral neck in men and the ultradistal radius in women. No major adverse effects.
The New England Journal of Medicine, 2006· 144 people
- 08SupaglutideBiologicModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 190 people given it.140 people given it2 trials
It lowered blood sugar well in newly diagnosed diabetes, and barely touched weight at the lower dose. A first stage split 140 people across three doses and a dummy. A second stage split 297 more to 1 mg, 3 mg or a dummy. At week 24 average blood sugar fell 1.73 points on 1 mg and 2.15 on 3 mg, ahead of the dummy by 1.26 and 1.68. Weight fell 0.97 and 3.14 percent, and only the higher dose beat the dummy. The sponsoring company's founder wrote the paper.
The numbers Two-stage seamless adaptive trial in drug-naive adults with newly diagnosed type 2 diabetes. Phase 2b randomised 140 participants across 1, 2 and 3 mg weekly and placebo; phase 3 randomised a further 297 to 1 mg, 3 mg or placebo. At week 24 glycated haemoglobin fell 1.73 percentage points on 1 mg and 2.15 on 3 mg, with treatment differences against placebo of 1.26 and 1.68 percentage points. 56 percent and 68 percent reached a glycated haemoglobin below 7.0 percent. Body weight fell 0.97 percent on 1 mg and 3.14 percent on 3 mg, and only the 3 mg weight difference against placebo was significant. Sponsored by Innogen Pharmaceutical; the corresponding author is the company's founder.
Diabetologia, 2026· 140 people
Added on top of metformin, it lowered blood sugar substantially. A first stage gave 1 mg, 3 mg or a dummy for 12 weeks, and average blood sugar fell 1.10 and 1.43 points. A second stage gave new participants 3 mg or a dummy for 24 weeks, then 28 more weeks in which everyone knowingly took the drug. Average blood sugar fell 1.80 points against 0.74 on the dummy. Side effects were mostly mild or moderate stomach complaints. Same company sponsor and same founder as the earlier trial.
The numbers The add-on to metformin trial. Phase 2b randomised to 1 mg, 3 mg or placebo for 12 weeks, at which point glycated haemoglobin had fallen 1.10 and 1.43 percentage points. Phase 3 randomised new participants to 3 mg or placebo for 24 weeks of double-blind treatment followed by a 28 week open-label extension; glycated haemoglobin fell 1.80 percentage points against 0.74 on placebo, an estimated treatment difference of 1.06 points. Adverse events were predominantly mild to moderate gastrointestinal events. Same sponsor and same founder as SUPER1.
Nature Communications, 2026· number of people not given
Also measured in animals or in the lab
In diabetic monkeys. One shot lowered blood sugar for a while, more at higher doses. Four weeks of weekly shots lowered fasting blood sugar. The monkeys ate less and lost weight, and they handled sugar better. This study is filed under the old name. It is one reason a search for supaglutide makes an approved drug look untested.
The numbers Diabetic rhesus monkeys. A single subcutaneous injection transiently reduced blood glucose dose-dependently; over four weeks of weekly dosing fasting and random glucose fell dose-dependently with declining plasma fructosamine, body weight decreased alongside reduced food intake, glucose tolerance improved and glucose-stimulated insulin secretion increased. A monkey study, indexed under the development name, and one of the reasons a search on supaglutide makes an approved medicine look preclinical.
Journal of Endocrinology, 2021· animal study
- 09MK-677Small moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 65 people given it.11 reported65 people given it1 trial1 found nothing
found nothingIt shifted muscle and fat, and it did not make anyone stronger or more able. 65 adults aged 60 to 81 took MK-677 or a dummy pill daily for up to two years. Growth hormone and IGF-1 climbed back to young-adult levels. Lean tissue rose about 1.1 kg while the dummy group lost about half a kilo. Strength and everyday function did not improve at all. Fasting blood sugar rose and the body handled insulin worse. That last sentence is the part people skip.
The numbers 65 adults aged 60 to 81 on MK-677 25 mg daily for up to 2 years: GH and IGF-1 rose to young-adult levels and fat-free mass increased 1.1 kg vs a 0.5 kg loss on placebo, but strength and function did not improve and fasting glucose and insulin resistance rose.
Annals of Internal Medicine, 2008· 65 people
What people using it report
- Blood sugar is what the more medically literate posters keep returning to. Raised fasting glucose and worsening insulin sensitivity are discussed as the expected trade rather than as a rare event, and running metformin alongside is described as a common response to that.
- 10SomatropinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 84 people given it.9 reported60 people given it1 trial
Take growth hormone away from adults who need it and most things get worse. 60 adults with a pituitary shortage, treated for about ten years, were switched onto a dummy for four months. Their IGF-1 fell sharply. Two aspects of quality of life declined. Waists grew, deep belly fat rose, and cholesterol and an inflammation marker worsened. One thing improved: their response to insulin got better. This is about people with a diagnosed shortage, not about anybody whose own levels are normal.
The numbers 60 hypopituitary adults on GH for a mean of 10 years were crossed over to four months of placebo. IGF-1 fell from 168 to 98 micrograms per litre, two quality-of-life domains deteriorated, waist circumference and visceral fat rose, and lipids and C-reactive protein worsened, while insulin sensitivity improved.
Journal of Clinical Endocrinology and Metabolism, 2012· 60 peoplepoints the wrong way
- 11MifepristoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 320 people given it.4 reported50 people given it1 trial
In Cushing's syndrome, where cortisol is the problem, blocking its receptor with mifepristone improved blood sugar, blood pressure and weight over six months. 50 adults took part, and there was no dummy pill group. Tiredness, nausea, headache and low potassium were common. This is the approved use, not a study of ageing.
The numbers 50 adults with endogenous Cushing's syndrome, after failed treatment, were given mifepristone 300 to 1,200 mg daily for 24 weeks, open-label, at 17 US centres. In the diabetes or impaired glucose tolerance group 60% had a glucose AUC response; HbA1c fell from 7.43% to 6.29% and fasting glucose from 149 to 105 mg/dL. In the hypertension group 38% had a diastolic pressure response. Mean weight change -5.7%; 87% judged clinically improved. Fatigue, nausea, headache, low potassium, arthralgia, vomiting, oedema and endometrial thickening were common.
The Journal of Clinical Endocrinology and Metabolism, 2012· 50 people
- 12LeptinBiologicModerate. At least one finished study in people, and at least 100 people who took it. 6 completed trials, 844 people given it.5 reported32 people given it2 trials
In partial lipodystrophy the drug did not clearly help. 23 patients with the partial form and either diabetes or very high blood fats took metreleptin for a year, with everybody knowing what they were getting. Average blood sugar drifted down by under a point and blood fats came down, but neither change was big enough to separate from chance. Nausea affected 39% and low blood sugar 26%. Partial lipodystrophy is still outside what the drug is approved to treat.
The numbers Open-label expanded access, 23 patients with partial lipodystrophy and diabetes or hypertriglyceridaemia, 1 year: mean HbA1c change -0.88 percentage points (SE 0.62), triglycerides -119.8 mg/dL (SE 84.1), numerically but not significantly lower. Nausea 39 percent, hypoglycaemia 26 percent. Partial lipodystrophy remains outside the approved indication.
Journal of Diabetes and Metabolism, 2016· 23 people
Leptin worked, and it worked in the disease it is now approved for. Nine women with lipodystrophy, a condition where body fat is lost from the places it belongs, had very low leptin and eight also had diabetes. They injected leptin twice a day for four months. Average blood sugar fell nearly two points, blood fats fell about 60% and liver size fell about 28%. Diabetes drugs were stopped or cut back. Everybody knew who was getting the drug. Public money paid for it.
The numbers Open-label, 9 women aged 15 to 42 with lipodystrophy and leptin below 4 ng/mL, 8 with diabetes, recombinant methionyl human leptin twice daily for 4 months. HbA1c fell 1.9 percentage points (95 percent CI 1.1 to 2.7) in those with diabetes; triglycerides fell 60 percent and liver volume 28 percent in all nine; antidiabetic drugs were stopped or greatly reduced. NIH and non-US government funded.
New England Journal of Medicine, 2002· 9 people
- 13MibavademabBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 1 person given it.1 people given it1 trial1 found nothing
found nothingThe antibody only worked in people who were already short of leptin. In an early study in people, compared with a dummy shot, it was well tolerated. In the authors' words, it reduced body weight over twelve weeks in people with low leptin in the blood, and had no effect on weight in people whose leptin was higher. One patient given it outside a trial had better triglycerides and less liver fat. In mice bred without leptin, it brought weight, eating and blood sugar back to normal.
The numbers A fully human antibody activating the leptin receptor with or without leptin. In obese leptin knockout mice it normalised body weight, food intake, blood glucose and insulin sensitivity. In a randomised double-blind placebo-controlled two-part phase 1 it was well tolerated. Verbatim: treatment of individuals with overweight or obesity decreased body weight over 12 weeks in those with low circulating leptin concentrations, under 8 ng/mL, but had no effect on body weight in individuals with higher baseline leptin. Compassionate use in one patient with atypical partial lipodystrophy and neutralising antibodies to metreleptin was associated with improvements in triglycerides and hepatic steatosis.
Science Translational Medicine, 2023· 1 people
- 14EfpeglenatideBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 4,076 people given it.3 reported0 people given it1 trial
Used on its own, the drug brought blood sugar down into a normal range. People with type 2 diabetes took it or a dummy injection for about seven months. Their three month average blood sugar started at 8.1 and finished somewhere around 6.4 to 6.9. They lost weight as well. Side effects looked like those of other drugs in this family, mostly stomach and bowel upset. This trial measured blood sugar and weight, not whether anyone lived longer.
The numbers HbA1c fell to 6.4% to 6.9% from 8.1% at 30 weeks with body weight reduction; tolerability similar to other GLP-1 RAs.
Diabetes Care, 2022· number of people not given
- 15MariTideBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.1 reported0 people given it1 trial
This is the company's own account of its trial, given at a conference. It reports up to about 20 percent weight loss in people with obesity after a year, and about 17 percent in people who also had type 2 diabetes. The figure quoted assumes people stayed on the drug. A full late stage programme has now started, and that is what will decide the question.
The numbers Up to about 20% weight loss (efficacy estimand) in obesity and about 17% with type 2 diabetes at 52 weeks; Phase 3 MARITIME program initiated.
Amgen press release, 2025· number of people not given
- 16DanuglipronSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.3 reported0 people given it1 trial
In people with type 2 diabetes, the pill moved everything in the right direction. Over 16 weeks it lowered average blood sugar, fasting blood sugar and body weight compared with a dummy. That is three things improving at once in a mid-sized trial. What happened to this drug afterwards is the part that matters, and it is in the entries below this one.
The numbers Reduced HbA1c, fasting glucose and body weight at 16 weeks versus placebo.
JAMA Network Open, 2023· number of people not given
- 17HRS-7535Small moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 235 people given it.2 reported0 people given it1 trial
Two large final-stage trials both came out positive. Over about a year, people taking the daily pill lost roughly 11% of their body weight, against a little over 2% on a dummy pill. In the separate diabetes trial, average blood sugar over three months fell by 1.5 to 1.7 percentage points. Both results arrived as a company announcement. Neither trial has been published in full, so the safety detail is not yet public.
The numbers About 11% weight loss at 50 weeks; HbA1c down 1.5% to 1.7%.
Kailera press release, 2026· number of people not given
- 18MyostatinBiologicModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 188 people given it.0 people given it1 trial
Blocking the receptor, not the hormone, caused big changes in body makeup. Adults with type 2 diabetes and obesity took bimagrumab or a dummy for 48 weeks. Fat fell by about a fifth, 7.5 kg, against almost nothing on the dummy. Muscle rose by 1.7 kg, waists shrank 9 cm, and average blood sugar fell by three quarters of a point. Note what this drug blocks. It shuts the receptor down, so it blocks activin A as well as myostatin.
The numbers Receptor-level blockade rather than myostatin-only blockade, so it neutralises activin A too. At 48 weeks fat mass fell 20.5% (7.5 kg) against 0.5% on placebo, lean mass rose 3.6% (1.7 kg), waist fell 9.0 cm and HbA1c fell 0.76 points, all p < 0.006.
JAMA Network Open, 2021· number of people not given
- 19LotiglipronSmall moleculePreliminary. Studied in people, but no published study has had people take it. 1 registered with no result.3 reported0 people given it1 trial
Lotiglipron worked on blood sugar and weight, and it was stopped anyway for safety. 901 people took at least one dose, 512 with type 2 diabetes and 389 with obesity. Some got a dummy pill. Average blood sugar fell by up to 1.44 points against almost nothing on the dummy pill. Weight fell by up to 7.47 percent against 1.84 percent. The study was stopped early for safety after a routine review. Nausea reached 60.6 percent at the highest obesity dose. Most people never reached their target dose.
The numbers Phase 2, randomised, double-blind, placebo-controlled, dose-ranging. 901 participants treated with at least one dose, 512 in the type 2 diabetes cohort and 389 in the obesity cohort. Terminated early for safety reasons after routine data and monitoring review, with planned analyses modified before unblinding. HbA1c fell across all doses at week 16 (p < 0.0001), by up to 1.44 percent (90% CI minus 1.63 to minus 1.26) against minus 0.07 percent on placebo. Weight fell across all doses at week 20 (p < 0.01), by up to 7.47 percent (90% CI minus 8.50 to minus 6.43) against minus 1.84 percent on placebo. Most participants on higher doses did not reach their target maintenance dose. Nausea ranged from 4 percent on placebo to 28.8 percent at 80 mg in diabetes, and 12.5 percent on placebo to 60.6 percent at 200 mg in obesity.
Diabetes, Obesity and Metabolism, 2025· number of people not given
- 20AdiponectinBiologicPreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it.2 reportednobody was given it2 watch-only studies
Adiponectin looks protective until you use genetics to test it, and then the link disappears. Inherited variants in up to 31,000 people were used as a natural experiment. Simply measuring the hormone, lower adiponectin went with higher fasting insulin and clearly higher diabetes risk. Being born with genetically lower adiponectin showed no such link, on either measure. The authors found no consistent evidence that raising adiponectin would improve insulin sensitivity or diabetes risk. The NIH paid for it.
The numbers ADIPOQ variants as instruments in up to 31,000 people, 2,969 with gold-standard insulin sensitivity, 15,960 diabetes cases and 64,731 controls. Observationally, 1 SD lower adiponectin went with 0.31 SD higher fasting insulin and diabetes odds of 1.75. Genetically lower adiponectin showed no association with fasting insulin (0.02 SD, 95 percent CI -0.07 to 0.11) or diabetes (OR 0.94, 0.75 to 1.19; genetic risk score OR 0.99 per allele). The authors found no consistent evidence that raising adiponectin would improve insulin sensitivity or diabetes risk. NIH funded.
Diabetes, 2013· 31,000 peopleobserved only, nobody was given it
Genetics points the harm the wrong way for anyone hoping to raise adiponectin. 356 people with type 2 diabetes in Italy were followed for about five and a half years, and 58 died of heart disease. Those carrying a gene variant that raises adiponectin died of heart disease about twice as often. The genetic signal was stronger than the plain observed one, which the authors read as evidence the paradox is real. Public money paid for it.
The numbers Gargano Heart Study, 356 patients with type 2 diabetes, mean follow-up 5.4 years, 58 cardiovascular deaths. The ADIPOQ variant rs822354 raised adiponectin and was associated with cardiovascular mortality (incidence rate ratio 1.94, 95 percent CI 1.23 to 3.07), with a genetic effect larger than the observational one, interpreted by the authors as evidence that the paradoxical association is causal. Non-US government funded.
Cardiovascular Diabetology, 2016· 356 peopleobserved only, nobody was given it
Also measured in animals or in the lab
In mouse cells and tissues. This paper found adiponectin's two receptors, AdipoR1 and AdipoR2. It showed they carry adiponectin's effects on fat burning and sugar uptake.
The numbers Identification of AdipoR1 and AdipoR2 and demonstration in mouse cells and tissues that they mediate adiponectin's effects on fatty acid oxidation and glucose uptake through AMPK and PPAR-alpha.
Nature, 2003· animal study
In mice. AdipoRon, a pill-type molecule, switched on both adiponectin receptors. It helped insulin work and improved blood sugar handling in mice on a high-fat diet. It did nothing in mice missing both receptors. It eased diabetes in a diabetic strain and lengthened their shortened lifespan. Mouse only. There is no human data.
The numbers AdipoRon, an oral small molecule binding AdipoR1 and AdipoR2, activated AMPK and PPAR-alpha, improved insulin resistance and glucose tolerance in mice on a high-fat diet (abolished in double knockouts), ameliorated diabetes in db/db mice and prolonged their shortened lifespan on a high-fat diet. Mouse only; no human data exist.
Nature, 2013· animal study
- 21ClenbuterolSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 11 people given it.5 reportednobody was given it1 watch-only study
Clenbuterol mixed into street heroin sent 34 people to emergency rooms across five US states. They arrived with racing hearts, low blood pressure, high blood sugar, low potassium and raised lactate. Six of them had blood evidence of damage to the heart muscle. The drug was confirmed in their blood. Nobody chose these doses and nobody was measuring anything in advance. This is a hazard report, not a study of the drug.
The numbers 34 probable or confirmed emergency department presentations across 5 US states over 6 months. Blood clenbuterol 2.4 to 26 ng/mL. Significant tachycardia, hypotension, hyperglycaemia, hypokalaemia and raised lactate; 6 of the patients had biochemical evidence of myocardial injury.
Annals of Emergency Medicine, 2008· number of people not givenobserved only, nobody was given it
- 22GYM329BiologicPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it, 1 registered with no result.1 reportednobody was given it1 watch-only study
Nobody has shown that a myostatin blocker improves blood sugar control in people. This trial is testing it in adults with type 2 diabetes who also carry extra weight. The reasoning is that muscle is where most of your blood sugar goes after a meal, so more muscle should mean better control. That chain has never been demonstrated with one of these drugs. Enrolment is closed and the trial is still running. No results have been posted.
The numbers The metabolic indication. Muscle is the main site of insulin-stimulated glucose disposal, so more muscle should improve insulin sensitivity. That chain has not been demonstrated with a myostatin antibody in humans.
ClinicalTrials.gov, 2026· number of people not givenobserved only, nobody was given it
What people using these actually report
These are people describing their own use. They come from clinic write-ups, complaint records kept by regulators, and public forums, and they are shown as written. They are the best guide on this page to what people actually do, what they expect, and what goes wrong. They cannot show that anything works. Nobody was compared with people on a dummy pill, and people who saw no effect mostly stopped posting. Both things are true at once. The bad reports are kept in for the same reason.
- Blood sugar is what the more medically literate posters keep returning to. Raised fasting glucose and worsening insulin sensitivity are discussed as the expected trade rather than as a rare event, and running metformin alongside is described as a common response to that.
Sources: Multi-page MK-677 side effects threads and a separate low-dose healthspan thread on ExcelMale, found by site-restricted search and read directly, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Mouth sores and rashes are the most consistently described problem, and people describe them settling when they pause or lower the dose. Raised blood glucose is discussed as an expected consequence rather than a surprise, insomnia is described after the first doses, and worry about lowered white blood cells and infection risk recurs without an answer.
Sources: Rapamycin experience and dosing threads on LongeCity, found by site-restricted search and read directly, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Bloodwork reports disagree with each other. Sharply raised LDL, the bad cholesterol, and raised liver enzymes after about a month at the higher amounts appear. So do reports of better blood fat results from other people. A raised fasting glucose reading appears and is then questioned by the same poster who raised it.
Sources: Cardarine threads on ExcelMale and MESO-Rx, with T-Nation and LongeCity threads surfaced by the same site-restricted search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Raised blood sugar and a worsened HbA1c are given as reasons for stopping. Erectile function is raised as a concern too, though less consistently and usually as a question rather than a report.
Sources: Statin threads on ExcelMale, found by site-restricted search and read directly, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Individual claims of large effects circulate, including a strikingly low glycated haemoglobin attributed to it, and the threads themselves push back on those as single uncontrolled observations rather than accepting them.
Sources: Carnosine experience, dosage and glycation threads in the LongeCity supplements forum, found by site-restricted search, September 2026. Nothing above is attributed to any specific post and no post is reproduced.
- Rising fasting blood sugar or HbA1c (a three-month blood sugar average) on follow-up blood tests. This is a known concern when you push the growth hormone system, and it is why clinics check it.
Sources: Fluid retention, arthralgia and glucose effects appear in the tesamorelin Phase 3 safety data and its FDA labelling, which is trial-derived. The sleep reports, the timelines and the abdominal fat impressions are from clinic write-ups and peptide user forums and are not from any trial of the blend. The 2026 Sports Medicine and Frontiers in Endocrinology reviews both say belief alone is a real contributor to what users report on unapproved peptides.
Measured in animals or in the lab, not yet in people
These are kept apart from the studies in people, not ranked against them. They answer a different question. A result in a rat is a real result, and a reason somebody ran the study. It is not a measure of what happens in you. When the work in people is missing, the reason is usually money, not failure. The bottom of this page explains why.
Peptides and blends
- 01HGH Fragment 176-191PeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, no human study.5 reported2 animal or lab studies
Measured in animals or in the lab
In obese rats, the tail end of growth hormone copied growth hormone's fat burning in fat tissue and slowed weight gain, without blood sugar problems.
The numbers The C-terminal 177-191 domain of hGH mimicked GH's lipolytic actions on adipose tissue and reduced weight gain in obese rats without insulin resistance.
Journal of Molecular Endocrinology, 2000· animal study
In rats, fed by mouth, over 19 days. That is where the fat-loss story for this fragment comes from. Fat rats given the peptide daily gained less than half the weight the untreated rats gained, and their response to insulin was not harmed. They swallowed it. People buy it as a shot. Nothing here was measured in a human, and nobody has checked whether a shot in a person does anything like this.
The numbers Oral AOD9604 at 500 mcg/kg for 19 days in obese Zucker rats reduced body-weight gain by over 50%, 15.8 plus or minus 0.6 g against 35.6 plus or minus 0.8 g in controls, with no adverse effect on insulin sensitivity by euglycemic clamp.
Hormone Research, 2000· animal study
- 02SHLP2PeptidePreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.6 reported2 animal or lab studies
Measured in animals or in the lab
In mice. Scientists found the switch SHLP2 presses, called CXCR7. Given by shot or into the brain, SHLP2 kept male mice from getting fat on a high fat diet, and helped insulin work better. It is the strongest paper on this peptide, and it is all animal work.
The numbers Identifies CXCR7 as the receptor SHLP2 binds and activates. Systemic and intracerebroventricular SHLP2 protected male mice from high fat diet induced obesity and improved insulin sensitivity, acting through POMC neurons in the arcuate nucleus. Male mice. This is the strongest mechanistic paper on the peptide and it is entirely preclinical.
Nature Communications, 2023· animal study
This paper found SHLP2 and five sister peptides. In people, it only measured blood levels, and they fall with age. Nobody was given anything. In rodents, SHLP2 put into the brain helped the body handle blood sugar. In a dish, it cut cell death and cell damage, and helped mitochondria run.
The numbers The naming paper. An in silico search of the 16S rRNA region of mitochondrial DNA that encodes humanin found six more short open reading frames, SHLP1 to SHLP6. SHLP2 and SHLP3 reduced apoptosis and reactive oxygen species and improved mitochondrial metabolism in vitro and enhanced 3T3-L1 preadipocyte differentiation in culture. Rodent clamp studies showed intracerebrally infused SHLP2 increasing glucose uptake and suppressing hepatic glucose production. It also reports that circulating SHLP2 declines with age in human plasma, which is a measurement, not an intervention.
Aging (Albany NY), 2016· lab (cells in a dish)
- 03AdipotidePeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.6 reported1 animal or lab study
Measured in animals or in the lab
In obese rhesus monkeys, adipotide killed off blood vessels in white fat. They lost 7.4 to 14.7% of their weight in four weeks and handled insulin better. Kidney changes grew with the dose and went away after stopping.
The numbers Adipotide induced apoptosis in white-fat blood vessels of obese rhesus monkeys, producing 7.4 to 14.7% weight loss in four weeks with improved insulin resistance; renal proximal tubule changes were dose-dependent and reversible.
Science Translational Medicine, 2011· animal study
- 04MOTS-c with SS-31BlendPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.6 reported1 animal or lab study
Measured in animals or in the lab
In mice made fat on a rich diet, MOTS-c shots lowered three kinds of fat and fuel breakdown products in the blood. These same markers run high in fat and diabetic mice. The paper says MOTS-c helped these mice use insulin better and burn more fat, so less was stored. This was mice only. The lead scientist advises and owns shares in a company making mitochondria peptides, and the paper says so.
The numbers In diet-induced obese mice, MOTS-c injection reduced three plasma metabolite pathways that are upregulated in obesity and type 2 diabetes models: sphingolipid, monoacylglycerol and dicarboxylate metabolism. The paper describes MOTS-c as improving insulin sensitivity and increasing beta oxidation to prevent fat accumulation in these mice. Mice only. The senior author discloses being a consultant and stockholder in a company developing mitochondrial peptides.
Physiological Reports, 2019· animal study
- 05Mitochondrial+ blendBlendPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.6 reported1 animal or lab study
Measured in animals or in the lab
In mice made fat on a rich diet, MOTS-c lowered three kinds of fat and fuel breakdown products in the blood. These markers run high in fat and diabetic mice. The paper says the mice used insulin better and burned more fat. This was mice only. The lead scientist advises and owns shares in a mitochondria peptide company, and the paper says so.
The numbers In diet-induced obese mice, MOTS-c reduced sphingolipid, monoacylglycerol and dicarboxylate metabolism pathways, which are upregulated in obesity and diabetes models, with the paper describing improved insulin sensitivity and increased beta oxidation. Mice. The senior author discloses a consulting and stockholding interest in a mitochondrial peptide company.
Physiological Reports, 2019· animal study
Supplements
- 01ApigeninSupplementPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported1 animal or lab study
Measured in animals or in the lab
In mice. This is the strongest evidence for blocking CD38, and it did not use apigenin. A strong, precise blocker called 78c reversed the fall in NAD with age. It improved blood sugar control, muscle function, exercise ability and heart function, in mice that aged normally or fast. An author holds a patent on CD38 blockers. 78c is not for sale and has no human data.
The numbers The strongest evidence for the CD38 strategy, and it was not generated with apigenin. 78c, a highly potent and specific thiazoloquinazolinone CD38 inhibitor, reversed age-related NAD decline and improved glucose tolerance, muscle function, exercise capacity and cardiac function in mouse models of natural and accelerated ageing. The effects depended on tissue NAD levels and were reversed by inhibiting NAD synthesis. A declared conflict: an author holds a patent on the use of CD38 inhibitors for metabolic disease. 78c is not commercially available and has no human data.
Cell Metabolism, 2018· animal study
Other compounds
- 01BAM15Small moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.2 reported1 animal or lab study
Measured in animals or in the lab
In mice. It improved blood sugar control.
The numbers Improved glucose tolerance.
EMBO Molecular Medicine, 2020· animal study
- 02Senolytic CAR T cellsBiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.1 animal or lab study
Measured in animals or in the lab
In mice. A single dose of the uPAR-hunting T cells helped normally ageing mice exercise more. It helped old mice and mice on a high-fat diet handle blood sugar better. The effect lasted, and it also worked as prevention.
The numbers Mouse. uPAR-positive senescent cells accumulate with age and were targetable with senolytic CAR T cells. A single administration improved exercise capacity in physiologically ageing mice and ameliorated metabolic dysfunction, including glucose tolerance, in aged and high-fat-diet mice, with long-lasting therapeutic and preventive effect.
Nature Aging, 2024· animal study
Why the trial record looks like this
A missing trial usually means nobody would pay for it. Nobody spends hundreds of millions of dollars on a molecule they cannot own. So the compounds with the thinnest record in people are often the oldest and easiest to get, not the weakest. Taking HGH Fragment 176-191 as the example, because it states the problem most clearly:
Two names, one molecule, and two very different evidence records. The difference is about filing, not about the drug. AOD-9604 is the end piece of growth hormone, pieces 177 to 191, with one extra building block added at the front to make it more stable. That is why it is often written hGH 176-191, or just GH fragment. Sold as AOD-9604, it carries a failed 24-week obesity study in 502 people and a project that was shut down. Sold as Fragment 176-191, it carries fat rats and a theory.
That mismatch is the whole story of this page. A buyer comparing the two pages would fairly guess that the fragment is less studied, so still an open question. In fact it is the same compound, with the negative result filed under the other name. The honest way to read this page is to read the AOD-9604 page. The honest thing to say about the difference is that it is a labelling accident.
Why nobody fixed it: the recipe is a piece of a human hormone published decades ago, so no company can own the plain fragment. The one company that owned a tweaked version already spent its money and got its answer. There is no business path to pay for a study of the plain fragment, and no scientific reason to expect it would answer anything the tweaked version did not. What remains is an open question. That is not a yes and it is not a no. It sits next to a no that was filed under a different name.
A compound shows up here only when a study on its own page names this goal and reports a result for it. Just naming it is not enough. Work in people, in animals and in the lab is counted separately and never mixed. People counts come from the study lines, and when in doubt they count low. Nothing here is advice. Nothing here tells you to take or to avoid anything.