By Julia Parker — JBizNews Desk
A peer-reviewed analysis published last month in Nature Reviews Endocrinology is intensifying scrutiny around what many researchers now view as the most important unresolved risk tied to the blockbuster Ozempic-class weight-loss drugs: significant muscle loss accompanying rapid reductions in body fat.
The paper, led by researcher Henning T. Langer, reviewed growing evidence that patients taking obesity injections such as Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound can lose substantial amounts of skeletal muscle alongside fat — a dynamic increasingly shaping the next multibillion-dollar phase of the pharmaceutical obesity market.
According to the review, as much as 25% to 40% of total weight lost on leading GLP-1 and dual-action obesity drugs may come from lean body mass rather than fat tissue alone. That finding is now driving a wave of investment into so-called “muscle-preserving” obesity therapies as drugmakers race to improve what physicians increasingly call the “quality” of weight loss rather than simply the quantity.
The concern is rooted in clinical trial data already embedded inside the industry’s biggest products.
In Novo Nordisk’s pivotal STEP-1 trial for semaglutide — the active ingredient in Ozempic and Wegovy — patients lost roughly 15% of body weight on average, while body-composition scans showed lean mass declines accounting for approximately 40% to 45% of total pounds shed.
Eli Lilly’s SURMOUNT-1 trial for tirzepatide — marketed as Mounjaro and Zepbound — produced even greater average weight reduction of roughly 21%, though lean mass losses represented closer to 25% of total weight lost.
Doctors broadly agree the drugs deliver major metabolic and cardiovascular benefits, including improvements in blood sugar, blood pressure, and heart-disease risk. But geriatric specialists are increasingly warning that rapid weight loss in older patients can create a condition known as “sarcopenic obesity,” where body weight improves on paper while muscle function and physical strength deteriorate underneath.
That risk is colliding directly with surging adoption rates.
Eli Lilly CEO David Ricks said earlier this year during an appearance on CNBC’s Squawk Box that between 20 million and 25 million people are currently taking obesity and diabetes medications from the two dominant manufacturers. Novo Nordisk CEO Mike Doustdar estimated the obesity-treatment population alone at roughly 15 million patients between the companies, while noting that approximately 110 million Americans are believed to live with obesity overall.
The demographic overlap worries researchers. According to the Centers for Disease Control and Prevention, nearly 40% of Americans over age 60 qualified as obese in 2023 — the same age group already most vulnerable to age-related muscle deterioration and frailty.
The financial stakes surrounding the market are enormous. Analysts at Barclays estimate the obesity-drug sector could generate roughly $150 billion annually within the next decade.
Eli Lilly projected 2026 revenue between $80 billion and $83 billion earlier this year, surpassing Wall Street expectations. Novo Nordisk, by contrast, warned of potential sales pressure after both companies agreed to “most favored nation” pricing arrangements negotiated with President Donald Trump last November, agreements expected to lower U.S. prices while expanding Medicare obesity-drug coverage later this year.
The next frontier in the obesity industry is increasingly focused on preserving muscle while maximizing fat loss.
Regeneron Pharmaceuticals presented data last year from its Phase 2 COURAGE trial showing that combining semaglutide with its experimental antibody trevogrumab preserved roughly 50% to 80% of the lean muscle mass typically lost during treatment with obesity drugs alone.
George D. Yancopoulos, Regeneron’s president and chief scientific officer, said the results demonstrated that blocking specific muscle-regulation pathways “can preserve muscle and further increase fat loss” when combined with Ozempic-style therapies.
The race has rapidly expanded across the industry.
Eli Lilly paid up to $1.9 billion in 2023 to acquire Versanis Bio and its muscle-preservation drug candidate bimagrumab. Phase 2b BELIEVE trial data presented at the American Diabetes Association last year showed the bimagrumab-semaglutide combination generated roughly 22.1% total weight loss, with nearly 93% of that reduction attributed specifically to fat rather than lean tissue.
Although Lilly later halted one of its mid-stage bimagrumab studies for what it described as “strategic business reasons,” the broader program remains active.
Other biotechnology firms including Scholar Rock, Biohaven, Veru, and Wave Life Sciences are also developing muscle-sparing therapies designed to pair with GLP-1 drugs. Wave Life Sciences CEO Paul Bolno recently told CNBC the company believes its experimental therapy could potentially “double the weight loss” achieved with obesity drugs while preserving strength and muscle quality.
For now, physicians are increasingly emphasizing lifestyle interventions alongside the medications themselves.
Researchers and geriatric specialists recommend resistance training and elevated protein intake — generally between 1.6 and 2.2 grams of protein per kilogram of body weight daily — to reduce muscle deterioration during rapid weight loss. Existing clinical studies suggest those interventions can reduce lean-mass decline by approximately 15% to 20%.
Another growing concern is weight cycling.
Researchers at the University of Copenhagen recently highlighted data involving more than 125,000 patients showing that between 46% and 65% of users discontinued obesity-drug treatment within 12 months. Separate meta-analysis data found that patients regained an average of roughly 21 pounds within about a year after stopping therapy.
The biological problem is asymmetrical: fat often returns faster than muscle can be rebuilt. Repeated cycles of loss and regain could therefore leave some patients physically weaker over time even if their body weight temporarily improves.
That dynamic is increasingly reshaping how pharmaceutical companies, doctors, and investors think about the obesity market itself.
The next generation of obesity medicine may no longer be judged simply by how much weight patients lose, but by how much strength, mobility, and muscle they manage to keep.
JBizNews Desk
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