[stock_market_widget type=”card” template=”basic2″ assets=”WVE” realtime=”true” api=”yahoo-finance”]
The newest weight loss drugs have changed what doctors expect from obesity treatment. Semaglutide, sold by Novo Nordisk A/S (NYSE: NVO) as Wegovy, produced average weight loss of about 15% in its main trial. Tirzepatide, sold by Eli Lilly and Company (NYSE: LLY) as Zepbound, delivered between 15% and 21%. That success raises an obvious question: how much of the lost weight is fat, and how much is muscle?
The answer depends on how you measure it. A review in Circulation calculated that lean mass made up about 34% of the weight lost in the main tirzepatide trial, and an even larger share in the semaglutide trial. A 2024 analysis pooling 22 randomized trials put the average closer to 25%. Lean mass is not the same thing as muscle, though. It also includes water and organs, so these figures likely overstate true muscle loss.
Some lean tissue loss is normal with any weight loss, including dieting and surgery, and researchers still debate whether the drug effect is a healthy adjustment or a real problem. The pooled analysis found lean mass as a share of body weight did not fall, so people generally ended up with a better ratio of muscle to fat. A study of 106 semaglutide patients found lean mass dropped about 3 kilograms in seven months and then held steady, while grip strength improved over the year.
Not every finding is as reassuring. A large analysis of U.S. health records, not yet peer reviewed, found tirzepatide users lost somewhat more lean mass than semaglutide users, with higher doses and longer use linked to bigger declines. Most researchers recommend pairing these drugs with resistance training and adequate protein.
That concern is the opening a Cambridge, Massachusetts, biotechnology company is aiming for. Wave Life Sciences, Inc. (NASDAQ: WVE) said it had started a Phase 2a trial combining its experimental drug WVE-007 with weekly tirzepatide. The study will test doses of 240 mg and 400 mg against placebo, with three patients receiving the drug for every one on placebo. Participants must have type 2 diabetes and a body mass index between 35 and 50. The company has not said how many people will enroll or when results are expected.
WVE-007 works differently from GLP-1 drugs. Rather than curbing appetite, it is a small interfering RNA, or siRNA, designed to silence a liver gene called INHBE. That gene makes a hormone, activin E, that appears to encourage fat storage. The idea comes from genetics. A 2022 study of more than 362,000 people found that those carrying broken copies of INHBE had less abdominal fat and healthier blood sugar and cholesterol levels
Wave says its clinical data so far show fat loss without muscle loss and support dosing once or twice a year. In animal studies, adding its INHBE drug to a GLP-1 doubled weight loss compared with the GLP-1 alone. Those are the company’s own characterizations, and animal results often fail to carry over to people. This trial is the first real test of whether the two approaches add up in patients.
Wave is also running a Phase 2a study of WVE-007 on its own. It expects to begin a separate trial in the second half of 2026 testing whether the drug can prevent weight regain after people stop GLP-1 treatment. Christopher Wright, the chief medical officer, noted that muscle matters beyond strength because it also shapes metabolism and the ability to keep weight off.
Raw weight loss may no longer be enough to stand out in the obesity market. As millions of people take these drugs, the quality of the weight they lose, and whether it stays off, is becoming the next competitive question. Wave is betting that a liver injection given once or twice a year can answer part of it, and this trial is where that bet meets real patients.
