Growing Use of GLP-1 Drugs Linked to Concerns Over Muscle and Bone Loss

The rapidly expanding use of GLP-1 receptor agonists and related incretin mimetics for weight management is raising concerns about their potential effects on muscle and bone health, according to a narrative review published in Obesity.

Researchers analyzed data from randomized clinical trials and observational studies evaluating liraglutide, semaglutide, and tirzepatide in people with overweight or obesity. As prescriptions for these medications have increased dramatically in recent years, scientists sought to better understand how they affect body composition, particularly in older adults.

The review found that treatment with incretin mimetics consistently led to reductions in lean body mass alongside weight loss. Depending on the medication and study, losses of lean soft tissue or fat-free mass ranged from 0.8 kg to 5.6 kg, accounting for approximately 12% to 44% of total weight lost. In the only study using MRI, tirzepatide was associated with an approximately 6% reduction in thigh muscle volume.

Several studies also reported decreases in bone mineral density, particularly at the hip and lumbar spine. In older adults at increased risk for fractures, semaglutide reduced bone mineral density at both sites, while similar findings were observed with liraglutide in adults with overweight or obesity. Some studies also showed increased levels of biochemical markers associated with bone resorption.

Despite these structural changes, the available evidence on physical function remains mixed. One semaglutide study found improvements in participants' self-reported physical function despite reductions in lean mass, while a liraglutide trial demonstrated better performance in a chair stand test compared with placebo.

Data on fracture risk are also inconclusive. In a large safety trial involving more than 17,000 older adults with diabetes, overall fracture rates were similar between semaglutide and placebo. However, among participants aged 75 years and older, fractures occurred more frequently in those receiving semaglutide.

The authors emphasize that although incretin mimetics are highly effective at reducing body weight, it remains unclear whether the observed losses in muscle and bone mass translate into poorer mobility or a greater risk of fractures over the long term. They call for larger, long-term studies focused on older adults and recommend that clinicians carefully monitor musculoskeletal health while prescribing these medications.

Follow NEWS.am Medicine on Facebook and Twitter