Metabolic
What does it do to the liver?
Fatty liver is the condition the metabolic drugs moved into next, so this is one of the fastest-growing evidence areas here.
8,636
people in trials
27
human studies
3
compounds, animal or cell only
7
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.
- 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
- 1,475 people2 human studies
1,075 postmenopausal women randomised to extract with 843 mg EGCG a day or placebo for one year. Adverse events 75.6 versus 72.8 percent; serious 2.2 versus 1.5 percent; more nausea and skin events on extract. ALT elevation in 36 (6.7 percent) versus 4 (0.7 percent), p < 0.001; 1.3 percent had ALT-related serious adverse events. US National Cancer Institute funded.
Food and Chemical Toxicology, 2015 · 1,075 people
Secondary analysis of the Minnesota trial (400 women on extract, 98 percent white, mean age 59.8). Mean ALT rose 78 to 82 percent from baseline at months 6 and 9 in UGT1A4 rs6755571 A/C carriers against 28 to 30 percent in C/C, p < 0.001 and p = 0.004. Points to a genetic component in who gets liver injury.
Journal of Dietary Supplements, 2023 · 400 people
- 1,075 people1 human study
1,075 postmenopausal women randomised to an extract delivering 843 mg EGCG a day or placebo for one year. Alanine aminotransferase elevation in 36 women on extract (6.7 percent) against 4 on placebo (0.7 percent), p < 0.001, with 1.3 percent having an ALT-related serious adverse event. Overall adverse event rates were similar, 75.6 against 72.8 percent, with more nausea and skin events on extract. US National Cancer Institute funded.
Food and Chemical Toxicology, 2015 · 1,075 people
- 293 people1 human study
48-week trial in 293 adults with biopsy-confirmed MASH: histologic improvement without worsening fibrosis in 47 to 62% on survodutide versus 14% on placebo.
New England Journal of Medicine, 2024 · 293 people
- 181 people1 human study1 found nothing
found nothingSYMMETRY, a Phase 2b trial in 181 patients with biopsy-confirmed compensated cirrhosis. The primary endpoint was missed: at 36 weeks fibrosis improved without worsening MASH in 19% on 50 mg against 13% on placebo. At 96 weeks the figures were 29% on 50 mg against 11% on placebo, a 16 percentage point difference (95% CI 2 to 30).
New England Journal of Medicine, 2025 · 181 people
- 145 people2 human studies1 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
The follow-on programme in steatohepatitis, which is the disease stage where liver fat matters clinically. Liver fat is a biomarker; fibrosis progression and liver outcomes are not.
ClinicalTrials.gov, 2026 · no headcount in the line
- 125 people1 human study
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
- 74 people1 human study
PROXYMO: 74 people with biopsy-proven non-cirrhotic MASH with fibrosis, randomised to cotadutide 600 mcg, 300 mcg or placebo for 19 weeks. At 600 mcg, absolute liver fat fraction fell 5.0 percentage points against placebo (95 percent CI 1.5 to 8.5), ALT fell 23.5 U per L and AST 16.8 U per L. Any adverse event in 91.7, 76.9 and 37.5 percent; discontinuation for adverse events 16.7, 7.7 and 4.2 percent. No histological endpoint. Sponsor funded.
Clinical Gastroenterology and Hepatology, 2024 · 74 people
- 61 people1 human study
61 people with HIV and NAFLD (NCT02196831) randomized to 12 months of tesamorelin 2 mg or placebo, with hepatic fat fraction as the primary endpoint.
The Lancet HIV, 2019 · 61 people
- 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
- 17 people3 human studies2 found nothing
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
found nothingThe finding that reframes the null trials. Using 14C-resveratrol in six volunteers, absorption of a 25 mg oral dose was at least 70% and peak plasma resveratrol plus metabolites reached about 2 micromolar with a 9.2 hour half-life, but only trace amounts of unchanged resveratrol were detectable. Rapid intestinal and hepatic sulfation is the rate-limiting step; glucuronidation and microbial hydrogenation of the double bond are the other routes.
Drug Metabolism and Disposition, 2004 · 6 people
found nothingTwenty overweight or obese men with NAFLD, 3,000 mg daily for eight weeks. No improvement in insulin resistance, steatosis, abdominal fat distribution, plasma lipids or antioxidant activity, and no change in NQO1, PTP1B, IL6 or HO1 transcription. ALT and AST rose significantly versus placebo through week 6, which the authors read as increased hepatic stress. A 2016 trial of 1.5 g daily for six months with paired biopsies also found no histological improvement, while a 2014 trial of 500 mg for 12 weeks alongside lifestyle advice did report improved inflammatory markers.
Clinical Gastroenterology and Hepatology, 2014 · no headcount in the line
- 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
Once-weekly pemvidutide reduced liver fat content in MASLD, with the glucagon component acting directly on the liver.
Journal of Hepatology, 2025 · no headcount in the line
Met MASH resolution without worsening of fibrosis at 24 weeks; did not meet fibrosis improvement at that timepoint.
The Lancet, 2025 · no headcount in the line
- no headcount stated2 human studies
ENLIVEN phase 2b, 222 randomised and 219 treated, biopsy-confirmed NASH with F2 or F3 fibrosis, 24 weeks. Fibrosis improvement without NASH worsening: 7 percent placebo, 22 percent on 15 mg weekly, 26 percent on 30 mg weekly (p 0.009), 27 percent on 44 mg every 2 weeks (p 0.008). NASH resolution: 2 percent placebo versus 37, 23 and 26 percent. Most common adverse events nausea and diarrhoea. Funded by 89bio.
New England Journal of Medicine, 2023 · no headcount in the line
128 randomised at 41 US centres, MASH with F2 or F3 fibrosis, efruxifermin 28 mg or 50 mg weekly or placebo. At 96 weeks, fibrosis improvement of at least one stage without MASH worsening: 19 percent placebo, 30 percent on 28 mg (difference 12 points, p 0.19), 49 percent on 50 mg (difference 31 points, 95 percent CI 12 to 49, p 0.003). Adverse events in 95 to 100 percent of every group including placebo. Sponsor Akero Therapeutics.
Lancet, 2025 · no headcount in the line
Also measured, in animals or cells
Transgenic overexpression of FGF21 markedly extended lifespan in mice without reducing food intake, apparently by blunting hepatic growth hormone and IGF-1 signalling. The same paper records that FGF21 blocks somatic growth and causes bone loss in mice. There is no human lifespan data.
eLife, 2012 · animal
- no headcount stated1 human study
Phase 2a substudy (NCT04881760): at 24 weeks, normal liver fat (below 5%) was reached by 86% of participants on 12 mg, 79% on 8 mg and 52% on 4 mg versus 0% on placebo.
Nature Medicine, 2024 · no headcount in the line
- no headcount stated1 human study
Oral NR raised blood NAD+ up to 2.7-fold in a human pilot and showed superior hepatic NAD+ kinetics in mice.
Nature Communications, 2016 · no headcount in the line
- no headcount stated1 human study
Fibrosis improvement without worsening of MASH at 24 weeks.
New England Journal of Medicine, 2023 · no headcount in the line
- no headcount stated1 human study
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
- no headcount stated1 human study
The safety report from the same 80-patient trial, 91.3 percent completion, average age 54, 71 percent female. No adverse drug reactions on hepatic, renal or glucose markers and no statistically significant self-reported or major adverse reactions. The stated conclusion is that pterostilbene is generally safe for use in humans up to 250 mg a day. It reports safety only and makes no efficacy claim.
Journal of Toxicology, 2013 · 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
Human plasma measurement in people without diabetes. Both MOTS-c and SHLP2 associated positively with android fat and liver fat. Worth reading carefully: the direction is positive, meaning higher peptide with more fat, which does not sit neatly with the mouse story in which giving the peptide protects against diet-induced obesity. An association in one direction and an intervention in the other are not in conflict, but neither can be used to predict the other.
Biochimica et Biophysica Acta, General Subjects, 2021 · no headcount in the line
Also measured, in animals or cells
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
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.
- 1 preclinical study
Measured in animals or cells
Reduced liver fat and oxidative stress in mice.
JCI Insight, 2025 · animal
- 1 preclinical study
Measured in animals or cells
Fifteen rhesus monkeys with biopsy-confirmed metabolic dysfunction-associated steatohepatitis, given weekly subcutaneous supaglutide at 50 or 150 micrograms per kg or placebo for three months. Liver fat measured by MRI proton density fat fraction fell 40 percent from baseline against placebo, and histological steatosis improved without worsening of fibrosis on ultrasound-guided biopsy. Fifteen monkeys, three months, no human liver endpoint has been tested.
- 1 preclinical study
Measured in animals or cells
The entire mouse lifespan case, from one laboratory. Empagliflozin extended the median survival of male mice by 5.9 percent, improved learning, memory and motor balance, lowered body weight, reduced hepatic P21 and P16, altered gut flora composition and raised short-chain fatty acids. A single-site study, not part of any multi-site replication programme.
GeroScience, 2024 · 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.
- Liver enzyme monitoring is standard clinical practice on danazol and is frequently absent from self-administered protocols.
Sources: Longevity forums and patient communities in aplastic anaemia and telomere biology disorders. Uncontrolled self-report, and the patient communities are describing a different population from the people considering it for ageing.
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 Supaglutide as the example, because it states the problem most clearly:
The gap between this compound's evidence and its visibility is the point of this batch.
By the standard this site applies to Western programmes, the diabetes case here is solid: two randomised, double-blind, placebo-controlled adaptive trials, one drug-naive and one on metformin background, both with prespecified phase 3 stages, both published in journals with real peer review, both reporting effect sizes in the range you would expect from a weekly GLP-1 agonist. That is more and better human evidence than most compounds documented on this site have.
It is also invisible in English. The reason is naming. The preclinical work says supaglutide. The trials say efsubaglutide alfa. The Chinese market says something else again. Nothing connects them in a search.
The honest reading is therefore split. For type 2 diabetes this is an approved drug with published pivotal trials. For weight loss it is a 50 person phase 2a signal with a published protocol for the larger trial, and any claim that it is an obesity drug is ahead of the data.
A note on what Chinese approval does and does not tell you. China's National Medical Products Administration requires trials in Chinese patients, and the pivotal trials behind these approvals are real randomised controlled trials published in mainstream journals, several of them in Diabetologia, Nature Communications, Diabetes Obesity and Metabolism and the Lancet regional title. What is usually missing compared with the Western incretin programmes is a cardiovascular outcome trial. Semaglutide and liraglutide carry cardiovascular outcome data in tens of thousands of patients followed for years; none of the compounds on this page does. So the correct statement is that these drugs are shown to lower glycated haemoglobin and body weight in Chinese adults over months, not that they are shown to prevent heart attacks. That gap is a real difference in the evidence, and it is separate from the question of whether a Western reader has heard of the drug.
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.