About 31% of weight lost by adults during GLP-1 therapy comes from lean mass
Key takeaways:
- In a meta-analysis of nine randomized controlled trials, adults had an average lean mass loss of 2.5 kg with GLP-1 therapy.
- More research is needed to examine the implications of lean mass loss with GLP-1s.
Lean mass constituted 30.8% of total body weight lost for adults who received a GLP-1 drug during a randomized controlled trial, according to findings published in Obesity.
Researchers conducted a systematic review and meta-analysis of nine randomized controlled trials assessing exenatide (Byetta, AstraZeneca), liraglutide (Victoza/Saxenda, Novo Nordisk), semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Eli Lilly) for the treatment of diabetes or obesity that reported on changes in fat mass, lean mass or bone mineral density as measured by DXA scan. Researchers found that most of the weight lost during GLP-1 therapy came from fat mass, but Kristen M. Beavers, PhD, MPH, RD, professor of internal medicine in the section of gerontology and geriatric medicine at Wake Forest University School of Medicine, noted that the proportion of body weight loss coming from lean mass is similar to what has been observed with bariatric surgery.
“While change in percentages (especially with small absolute numbers) can be deceptive, it does call attention to the possibility of additional mechanisms of lean mass loss that accompany GLP-1-based therapy,” Beavers told Healio.
There were 659 participants included in the meta-analysis, of whom 419 received a GLP-1-based medication and 240 received placebo (mean age, 41.7 years; 75% women). Five trials used medication doses indicated for obesity treatment, and the remaining four used doses indicated for diabetes management. Liraglutide was the medication evaluated in six trials, with exenatide, semaglutide and tirzepatide assessed in one trial each.
Participants receiving a GLP-1 drug had a mean 8.1 kg body weight reduction compared with a 1.2 kg weight loss for those receiving placebo. Adults using a GLP-1 drug had a 5.4 kg decrease in fat mass and a 2.5 kg loss in lean mass. The reduction in lean mass comprised 30.8% of total mass lost with GLP-1 therapy.
“The clinical relevance of GLP-1 receptor agonist-induced muscle mass loss is an active area of discussion, and more data are needed associating lean mass loss with clinical endpoints to aid in interpretability,” Beavers said. “That said, we felt an important and timely contribution to the field was to quantify the magnitude of loss reported in the literature.”
Only two trials in the meta-analysis reported on BMD change. One trial found once-weekly exenatide 2 mg was associated with a greater increase in lumbar spine BMD at 3 months compared with placebo. The second trial reported no change in total body BMD for adults receiving once-daily liraglutide 3 mg compared with placebo.
Beavers said several questions remain to be answered in future studies, included what the clinical implications of lean mass loss could be with GLP-1s, what happens to lean mass and BMD if GLP-1 therapy is stopped and whether interventions could minimize the loss of lean mass and bone mass with GLP-1s.
For more information:
Kristen M. Beavers, PhD, MPH, RD, can be reached at kbeavers@wakehealth.edu.
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