How do glucagon‐like Peptide‐1 receptor agonists affect measures of muscle mass in individuals with, and without, type 2 diabetes: A systematic review and meta‐analysis

Summary Glucagon‐like peptide‐1 receptor agonists (GLP1RAs) are used for the management of type 2 diabetes (T2DM) and obesity. GLP1RAs induce significant weight loss but concerns have been raised regarding the associated effects on muscle mass (MM). We therefore conducted a systematic review and meta‐analysis assessing the effects of GLP1RAs on various measures of MM in individuals living with overweight or obesity, with and without T2DM. Comprehensive search of Medline, Pubmed, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. Studies involving cohorts with a mean age over 40 years and a mean body mass index over 25 kg.m ‐2 were included. The primary outcome was any measure used to estimate MM, whilst fat mass (FM) and total body weight were included as secondary outcomes. Thirty‐eight publications, involving 1735 participants, were included in the review. Separate meta‐analyses were performed for studies involving participants with T2DM and individuals without T2DM (non‐DM). In individuals with T2DM, GLP1RAs induced a non‐significant mean reduction in MM measures (‐0.74 kg, 95% CI: ‐1.61, 0.14, p = 0.10), despite significantly reducing FM (‐3.18 kg, 95% CI: ‐4.09, ‐2.28, p < 0.0001). In the non‐DM analysis, a significant mean reduction in MM measures was observed (‐1.41 kg, 95% CI: ‐2.12, ‐0.71, p = 0.0001), however, this was significantly less than the reduction in FM (‐6.02 kg, 95% CI: ‐7.53, ‐4.50, p < 0.0001). In both populations, the reduction in measures of MM accounted for less than 20% of the total weight reduction. These findings provide some clarity to clinicians that use GLP1RAs to manage individuals with T2DM and/or obesity, however, further more detailed analysis of the impact of these medications on functional skeletal muscle is required.