Semaglutide is a GLP-1 receptor agonist used to treat obesity and type 2 diabetes, sold under names including Ozempic and Wegovy. Most of the research reaching the news cycle right now does not ask whether it works, but what it is being measured against and what comes off the body along with the fat.

Head to head with retatrutide

Eli Lilly said in October that in a large diabetes study, people on the highest dose of its investigational triple agonist retatrutide saw a 2.2 percentage-point reduction in A1c at 80 weeks, compared with 1.8 points for those on Ozempic. Weight loss in the same comparison was 20.9% on the highest retatrutide dose against 9.4% on Ozempic.

Those figures come from Lilly's own announcement and are based on analyses of participants who stayed on treatment, not all participants. That is a meaningful caveat on a number that looks dramatic in a headline.

The muscle question, in monkeys

The more interesting research direction is not more weight lost but what kind. iBio reported body-composition data from an eight-week study in obese non-human primates in which fat accounted for 93% of the weight lost by animals given semaglutide plus a single dose of its Activin E antibody IBIO-610, against 77% in animals on semaglutide alone.

This was six monkeys per group over eight weeks, and the release did not state total weight lost by either group or give lean mass in absolute terms. iBio says first-in-human studies are planned for the first half of 2027.

An add-on pill in human trials

Sironax said on 13 October it has reached roughly 50% of targeted enrollment in FORGE-LM, a double-blinded, randomized, placebo-controlled Phase 2 trial of its NAMPT activator SIR4156 alongside semaglutide in adults with obesity. The primary objective is the effect on body fat mass and composition, with lean mass sitting among the secondary objectives.

The supporting data so far are preclinical, including mouse work presented in Boston. Sironax notes that SIR4156 is not approved by any regulator and that its safety and efficacy in humans have not been established.

What Isn't Established

None of the muscle-preservation work has produced human results. The iBio figures are primate data at n=6 per group, and the company's own forward-looking statements flag that primate findings may not replicate in people.

The retatrutide comparison is a company statement about a competitor's marketed drug, not a published paper, and it covers a diabetes population specifically. No source here reports how much lean mass people on semaglutide actually lose, which is the question all three programs are circling.

Where the evidence stands

Semaglutide itself is now the comparator rather than the subject: it is the benchmark other candidates are tested against and the backbone other drugs are added to. The quality-of-weight-loss question that drives both add-on programs remains open, with one trial half-enrolled and the other not yet in humans.