THE CLASS PICTURE
GLP-1 medicines, fat mass and lean mass
Scale weight is not the same as fat loss. Total weight cannot distinguish fat, lean tissue, water and bone — and under GLP-1 and multi-agonist therapies, all four compartments can move. The class-wide DXA record is the context in which the retatrutide body-composition question is asked.
What the landmark trials measured — and what they did not
STEP 1 (semaglutide 2.4 mg, NEJM 2021) ↗ reported −14.9% mean weight change at 68 weeks versus −2.4% with placebo. SURMOUNT-1 (tirzepatide, NEJM 2022) ↗ reported −15.0% to −20.9% at 72 weeks. Both support the potency of the class; neither primary paper breaks body weight into fat and lean compartments.
The composition data came from substudies. The SURMOUNT-1 DXA substudy ↗ (n=160) measured −33.9% fat mass and −10.9% lean mass at week 72 — roughly 75% of weight lost as fat, ~25% as lean mass, in both active and placebo arms. The SUSTAIN 8 substudy ↗ measured semaglutide 1.0 mg reducing fat mass by 3.4 kg and lean mass by 2.3 kg over 52 weeks, without a placebo arm. Both support the same directional statement — fat dominates, lean moves too — and both carry the DXA caveat: lean mass includes water and non-muscle lean tissue.
Aggregated, the 35-trial systematic review ↗ puts the median at ~28.3% of weight lost on incretin therapies from muscle-based indices, with two-thirds of studies above the ~25% benchmark — and, pointedly, no objective physical-function outcomes in any included study.
Where retatrutide sits in the class
Retatrutide adds glucagon-receptor agonism to GIP and GLP-1. The phase 2 obesity trial (NEJM 2023 ↗) reported weight loss up to −24.2% at 48 weeks; the phase 2 DXA substudy in type 2 diabetes ↗ measured fat mass falling up to 26.1% at week 36, with the lean-mass share reported as similar to other obesity treatments. Read against the class benchmarks, retatrutide looks consistent rather than exceptional on composition — with the important limit that its DXA evidence is one substudy, in one population, over 36 weeks.
The full retatrutide-specific reading is at retatrutide and lean mass: the body-composition evidence; the muscle question at does retatrutide cause muscle loss?.