Recorded under Weight, alongside 4 other indications.

Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. MK-677

   human RCT Direct outcome Not approved for this condition

   Who was studied

   healthy older adults aged 60-81, n=65 completing year 1 (43 MK-677, 22 placebo), 25 mg orally daily, 12 months with a 2-year exploratory extension

   Both compartments were measured. Fat-free mass rose 1.1 kg (0.7 to 1.5) against a fall on placebo, while total fat mass did not differ between groups and abdominal visceral fat did not fall (+8.4 cm2 vs +4.2 cm2, p=0.68) - so the lean gain was not accompanied by fat loss. The same trial recorded fasting blood glucose up 0.3 mmol/L (p=0.015), HbA1c up 0.2% (p=0.002) and a significant decline in insulin sensitivity, and the fat-free mass gain produced no change in measured strength or function. No regulator has approved it for any indication.

   Source PubMed Central 1 primary source read for this row

2. Retatrutide

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with type 2 diabetes and overweight or obesity; a prespecified substudy of a phase 2 placebo- and dulaglutide-controlled trial, 36 weeks; the substudy sample size is not established from the abstract read

   The substudy measured both compartments by DXA, with percent change in total body fat mass at week 36 as its primary endpoint; total fat mass fell more than with placebo or dulaglutide, and the proportion of lean mass lost relative to total weight lost was reported as similar to other obesity treatments - lean mass fell alongside fat. The separate 48-week phase 2 obesity trial reported body weight only (22.8% and 24.2% reductions at 8 mg and 12 mg), which is not a composition measure. Retatrutide is investigational and approved by no regulator.

   Source PubMed 2 primary sources read for this row

3. Tesamorelin

   human RCT Direct outcome Not approved for this condition

   Who was studied

   HIV-infected adults with lipodystrophy and excess abdominal fat, mean age 48, 84-86% male; n=273 vs 137 placebo (study 1) and n=270 vs 126 placebo (study 2), 26 weeks with a 26-week extension

   Both compartments were measured: visceral adipose tissue by CT at L4-L5 fell 27 cm2 (-18%) and 21 cm2 (-14%) against placebo, and lean body mass rose 1.3 kg and 1.2 kg. The FDA label states the drug is weight-neutral and is not indicated for weight loss, and it records elevated HbA1c (>=6.5%) in 5% on tesamorelin vs 1% on placebo, hazard ratio 3.3. The FDA approval is for reduction of excess abdominal fat in HIV-infected adults with lipodystrophy only; there is no approval, and no trial on file, in people without that diagnosis.

   Source DailyMed — the FDA label 2 primary sources read for this row

4. CJC-1295 DAC

   human RCT Mechanistic only Not approved for this condition

   Who was studied

   healthy adults aged 21-61, two randomised placebo-controlled trials of 28 and 49 days; sample size not reported in the abstract

   Recorded, and not evidence for this condition

   The trials measured peak concentration and area under the curve of GH and IGF-1 and standard pharmacokinetic parameters. No study measured body composition: neither lean mass nor fat mass was assessed, and a rise in GH or IGF-1 is not a composition outcome. A registered trial in HIV patients with visceral obesity (NCT00267527) was terminated in September 2006 with no results posted.

   Source DOI 2 primary sources read for this row

5. Sermorelin

   human RCT Mechanistic only Not approved for this condition

   Who was studied

   prepubertal children with idiopathic growth hormone deficiency, 30 mcg/kg/day subcutaneously, 12 months

   Recorded, and not evidence for this condition

   The registrational outcome was height velocity in growth-hormone-deficient children. No study measured body composition: neither lean mass nor fat mass was assessed, in that population or any other. The FDA approval (Geref, NDA 019863) is for short stature associated with paediatric growth hormone deficiency; there is no approval for any body composition indication and no trial in adults without that diagnosis on file.

   Source FDA label 1 primary source read for this row

6. SS-31

   human RCT Mechanistic only Not approved for this condition

   Who was studied

   adults with genetically confirmed primary mitochondrial myopathy, n=218 (109 elamipretide, 109 placebo), mean age 45.6, 64% women, 40 mg/day subcutaneously, 24 weeks

   Recorded, and not evidence for this condition

   MMPOWER-3 measured distance on the 6-minute walk test and total fatigue on a symptom scale, and did not meet either primary endpoint in the overall population. No study measured body composition: neither lean mass nor fat mass was assessed, and the link from mitochondrial bioenergetics to a change in the lean-to-fat ratio is an argument, not a result. The enrolled population had a diagnosed mitochondrial disease and does not stand in for anyone else.

   Source NCBI 2 primary sources read for this row

7. Ipamorelin

   human observational Mechanistic only Not approved for this condition

   Who was studied

   healthy human volunteers in a pharmacokinetic-pharmacodynamic study; sample size and duration not reported in the abstract

   Recorded, and not evidence for this condition

   What was measured was GH release and the pharmacokinetic-pharmacodynamic relationship. No study measured body composition - neither lean mass nor fat mass was assessed in any human trial on file. The only registered human efficacy trial (NCT01280344) had recovery of gastrointestinal function after bowel resection as its endpoint, which is unrelated to body composition.

   Source DOI 2 primary sources read for this row

8. 5-Amino-1MQ

   animal in vivo Surrogate marker Not approved for this condition

   Who was studied

   diet-induced obese mice maintained on a high-fat diet; sample size and duration not reported in the abstract read

   In mice, 5-amino-1-methylquinolinium limited gains in body weight and white adipose tissue mass, reduced adipocyte size and lowered total plasma cholesterol. Only the fat compartment was measured; lean mass was not reported, so no ratio of lean to fat mass was established. The later mouse work that reported normalised body composition tested the inhibitor together with a reduced-calorie diet, so nothing there is attributable to the compound by itself. There is no human study of any kind on file.

   Source DOI 2 primary sources read for this row

9. IGF-1 LR3

   animal in vivo Mechanistic only Not approved for this condition

   Who was studied

   guinea pigs, continuous infusion of Long R3 IGF-I; sample size and duration not reported in the abstract

   Recorded, and not evidence for this condition

   What was measured in guinea pigs was organ growth and circulating IGF-I, IGF-II and IGF binding protein concentrations, which fell. No study measured body composition in any species: neither lean mass nor fat mass was assessed. A separate animal study reported that IGF-1 LR3 did not promote growth in growth-restricted fetal sheep. No human study is on file.

   Source DOI 2 primary sources read for this row

Recorded absences

1 compound is listed here without a rung. Each row exists to mark a distinction a reader would otherwise draw wrongly, and each says what is missing rather than leaving the compound off the page.

1. CJC-1295 no-DAC

   No rung — nothing on file to grade Not approved for this condition

   This row records an absence, not a finding. The record carries no evidence rung and none of its eight citations is graded; no trial, registry entry or regulator document measuring lean mass, fat mass or any other body composition outcome for CJC-1295 without DAC was located. The modified GRF(1-29) fragment sold under this name is a different molecule from the DAC-conjugated compound, and evidence for the latter does not transfer to it.

Checked, and nothing recorded

1 compound was checked against body recomposition and produced no gradeable row.

• AOD-9604 — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.