Clinicians turn to muscle preservation and nutrition on GLP-1 therapy

At the American Diabetes Association's 2026 Scientific Sessions, a symposium on GLP-1 receptor agonists spent significant time on a side effect that gets less attention than nausea or cost: muscle loss. Doctors said the newest, higher-dose incretin drugs can shift how much of a person's weight loss comes from muscle rather than fat, and they are now urging protein intake and structured exercise alongside the medications ^[1].

Muscle loss and the numbers

Ian Neeland, MD, director of cardiovascular prevention at University Hospitals Harrington Heart & Vascular Institute, told the symposium that roughly 25% of total weight loss from any intervention — diet, medication, or surgery — typically comes from lean body mass. With newer, higher-dose GLP-1 compounds, he said, that share can climb to 40% or more ^[1]. The stakes go beyond appearance: Neeland said each kilogram of muscle lost cuts resting energy expenditure by about 13 kilocalories, compared with 4 kilocalories for a kilogram of fat lost, meaning muscle loss can make it harder to keep weight off over time ^[1].

What clinicians are recommending

Neeland pointed to the S-LITE trial, in which people combined liraglutide with supervised resistance and aerobic training. That combination not only produced more weight loss but let some patients gain lean mass, an outcome not seen with medication alone ^[1]. He cited evidence supporting a protein intake of 1.2 to 1.6 grams per kilogram of body weight per day, with little added benefit above that range ^[1]. Separately, dietitian Patti Urbanski, who helped write the ADA's 2026 nutrition consensus statement, outlined targets from a 2025 obesity nutrition report: protein at 1.5 g/kg/day, fiber at 25 to 35 grams daily depending on sex, at least 2 liters of water, and a food-first approach using smaller plates and lean proteins ^[1]. She said trials show involving a registered dietitian can cut GLP-1 discontinuation rates by 5% to 10%, and likely more in everyday practice ^[1].

On the drug-development side, the experimental combination of semaglutide with the myostatin inhibitor bimagrumab, tested in the phase 2 BELIEVE trial, reduced the lean-mass share of weight loss from about 21% to 7% ^[1]. But Neeland noted a gap: there is little large-scale trial data measuring actual muscle function, and no clear clinical standard for how to measure it ^[1].

The symposium also covered osteoarthritis. In the STEP 9 trial, semaglutide 2.4 mg produced a mean weight loss of 13.7% in people with knee osteoarthritis and cut WOMAC pain scores by 41.7 points, versus 27.5 points in a structured-care comparison group, with less use of pain medications including opioids ^[1]. Notably, topline data from the TRIUMPH 4 trial showed tirzepatide's larger 23% weight loss produced pain relief similar to semaglutide's smaller 13% loss, suggesting joint benefits may not simply track with pounds lost ^[1].

Why it matters for patients

For people taking or considering semaglutide, tirzepatide, or other GLP-1 drugs, this shift in clinical thinking means the scale number alone may not capture what is happening to the body. Losing a large share of muscle along with fat could affect strength, metabolism, and long-term weight maintenance, according to the data presented ^[1]. The emerging guidance pairing these drugs with protein intake and resistance training reflects an attempt to protect muscle while still losing fat, though researchers acknowledged that standardized tools to measure muscle function in the clinic are still lacking ^[1].

What happens next

Sources reviewed do not specify when trials like BELIEVE or TRIUMPH 4 will report final results, or when formal guidelines on protein and exercise for GLP-1 users might be issued. Full peer-reviewed results and dosing guidance beyond the conference presentation are not yet available in the material reviewed ^[1].