Metabolic
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.
139,450
people in trials
100
human studies
8
compounds, animal or cell only
28
trials found nothing
Measured in people
Ranked by how many people, which is a fact about the evidence and not a judgement about the compound. The one at the top is the most studied, which is not the same as the best. Counts are never added across compounds, because the same person can appear in more than one trial.
- 31,356 people2 human studies
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 people
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 people
Also measured, in animals or cells
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
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
- 28,250 people4 human studies
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
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
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
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
- 27,692 people4 human studies2 found nothing
found nothingMeta-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 people
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 people
found nothing40 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 people
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 · no headcount in the line
- 15,178 people2 human studies
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
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
- 9,340 people1 human study
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
- 7,020 people1 human study1 found nothing
found nothingEMPA-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
What people using it report
- Euglycaemic diabetic ketoacidosis is the serious one, and community discussion repeatedly underestimates it because blood glucose looks normal while it is happening. Fasting, low carbohydrate intake, acute illness and surgery all raise the risk, and a glucometer will not warn you.
- 5,169 people1 human study
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 people
- 2,181 people3 human studies
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
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
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
- 1,655 people2 human studies
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
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 · 814 people
- 1,298 people2 human studies
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
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
- 1,261 people2 human studies
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 people
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 · no headcount in the line
- 1,206 people1 human study
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
- 1,147 people3 human studies
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
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
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
- 901 people1 human study
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 · 901 people
- 731 people1 human study
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
- 651 people1 human study
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
- 599 people1 human study
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
- 560 people3 human studies1 found nothing
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
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 nothing36 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
- 480 people3 human studies
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
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 · no headcount in the line
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 · no headcount in the line
- 361 people4 human studies2 found nothing
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
found nothingThe 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 · no headcount in the line
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 · no headcount in the line
found nothingSingle-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 · no headcount in the line
- 357 people8 human studies7 found nothing
found nothingThe 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 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 nothingNineteen 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
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 cells
found nothingThe 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 · in vitro
- 336 people1 human study
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
- 314 people1 human study
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 people
Also measured, in animals or cells
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
- 272 people1 human study
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
- 145 people1 human study1 found nothing
found nothing145 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
- 140 people2 human studies
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
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 · no headcount in the line
Also measured, in animals or cells
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
- 103 people1 human study
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
- 80 people2 human studies2 found nothing
found nothing60-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 nothing10-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 · no headcount in the line
Also measured, in animals or cells
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
- 75 people1 human study
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
- 74 people2 human studies
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
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 · no headcount in the line
- 65 people1 human study1 found nothing
found nothing65 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
- 64 people1 human study
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
- 60 people1 human study
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 people
- 53 people1 human study
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
- 37 people2 human studies2 found nothing
found nothing37 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 nothing48 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 · no headcount in the line
- 36 people1 human study
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
- 32 people2 human studies
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
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
- 30 people1 human study1 found nothing
found nothing30 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 people
Also measured, in animals or cells
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
- 30 people1 human study1 found nothing
found nothing30 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
- 30 people1 human study1 found nothing
found nothing30 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
- 23 people1 human study
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 people
Also measured, in animals or cells
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
- 20 people1 human study1 found nothing
found nothing20 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
- 16 people1 human study
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 · 16 people
- 13 people2 human studies2 found nothing
found nothingSeven 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, 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
- 8 people1 human study
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
- 1 people1 human study1 found nothing
found nothingA 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
- no headcount stated2 human studies
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 · no headcount in the line
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 · no headcount in the line
- no headcount stated1 human study1 found nothing
found nothingSummary 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 · no headcount in the line
Also measured, in animals or cells
The hGH 177-191 lipolytic domain stimulated hormone-sensitive lipase and reduced weight gain in obese rats without inducing insulin resistance or glucose intolerance.
- no headcount stated1 human study
Phase 3: HbA1c fell 1.24 to 1.48 points at 40 weeks versus 0.41 with placebo.
New England Journal of Medicine, 2025 · no headcount in the line
- no headcount stated1 human study
Placebo-corrected HbA1c reduction of 0.4% at 24 weeks with improved postprandial glucose and no weight gain.
Diabetes Care, 2013 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
52-week Phase 3 non-inferiority trial versus dulaglutide in type 2 diabetes on metformin.
The Lancet Diabetes and Endocrinology, 2025 · no headcount in the line
- no headcount stated1 human study
Reduced HbA1c, fasting glucose and body weight at 16 weeks versus placebo.
JAMA Network Open, 2023 · no headcount in the line
- no headcount stated1 human study
Glycemic benefit alongside weight loss.
Novo Nordisk press release, 2026 · no headcount in the line
- no headcount stated1 human study
About 11% weight loss at 50 weeks; HbA1c down 1.5% to 1.7%.
Kailera press release, 2026 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
A randomised controlled trial in resistance-trained males examining metabolic rather than hypertrophic endpoints, specifically fat oxidation and insulin sensitivity. Included because it is a second randomised human study of the same molecule from an independent group and a different source material.
Journal of Nutritional Science and Vitaminology, 2025 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study1 found nothing
found nothingRandomised 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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
Measured in animals or cells, not yet in people
These are separated from the trials above rather than ranked against them, because 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 measurement of what happens in you. Where the human work is missing, the reason is usually money rather than failure, and that is set out at the bottom of this page.
- 2 preclinical studies
Measured in animals or cells
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
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 · in vitro
- 1 preclinical study
Measured in animals or cells
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.
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
Improved glucose tolerance.
EMBO Molecular Medicine, 2020 · animal
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
What people using these actually report
Uncontrolled self-reports, gathered from clinic write-ups, regulatory complaint records and public forums, and reproduced here as written. They are the best guide on this page to what people actually do, what they expect, and what goes wrong, and they cannot show that anything works, because nobody was measured against a placebo and the people who saw no effect mostly stopped posting. Both halves of that are true at once. The negative reports are kept in for the same reason.
- Euglycaemic diabetic ketoacidosis is the serious one, and community discussion repeatedly underestimates it because blood glucose looks normal while it is happening. Fasting, low carbohydrate intake, acute illness and surgery all raise the risk, and a glucometer will not warn you.
Sources: Longevity forums, diabetes communities and clinic write-ups. Uncontrolled self-report, useful for knowing what to watch for and worthless as evidence of an ageing effect.
- Rising fasting glucose or HbA1c on follow-up bloods, which is a documented concern with growth hormone axis stimulation and is the reason 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 flag the placebo effect as a real contributor to what users report on unapproved peptides.
- Higher fasting glucose on bloodwork, which is the most commonly reported laboratory change.
Sources: Peptide and bodybuilding forums including r/peptides, plus clinic write-ups. Uncontrolled self-reports. The appetite and fluid retention effects also appear in the controlled literature on sustained ghrelin-receptor agonism.
Why the trial record looks like this
A missing trial is usually a missing sponsor. Nobody runs a nine-figure programme on a molecule they cannot own, so the compounds with the thinnest human records are often the oldest and most freely available ones rather than the weakest. Taking SHLP2 as the example, because it states the problem most clearly:
SHLP2 is best read as one member of a class, because the class-level summary is the honest one. The mitochondrial-derived peptides now comprise humanin and its nuclear-encoded isoforms, MOTS-c, and SHLP1 through SHLP6. As of this review date there is exactly one registered interventional human trial of any mitochondrial-derived peptide anywhere in the world, it is for MOTS-c, it is recruiting, and it will not report before 2028.
Every other piece of human data in the entire class is observational: levels measured in plasma, muscle, semen or cerebrospinal fluid and correlated with age, exercise, fat mass or disease. Those observations are genuine and they are interesting. They are not evidence that administering the peptide does anything.
Among the six SHLPs, SHLP2 carries nearly all of the literature. SHLP1 and SHLP4 through SHLP6 are barely characterised beyond the naming paper, and anything sold or written about them is extrapolation from SHLP2 and humanin.
A compound appears here only when a citation on its own page states this outcome and reports a result for it; naming it is not enough. Human, animal and cell work are counted separately and never merged. Participant counts are read from the study lines and deliberately undercount. Nothing here is advice, and nothing here is a recommendation to take or to avoid anything.