GLP-1RAs and SGLT2 inhibitors cause significant lean body mass loss, accounting for 28% of total weight reduction

GLP-1RAs and SGLT2is are widely used for obesity and type 2 diabetes mellitus (T2DM) due to their efficacy in weight loss and glycemic control. While effective, significant weight loss can often be accompanied by a reduction in lean body mass (LBM), which is crucial for metabolic health, strength, and overall function. Preserving LBM during weight loss is a key clinical challenge, as its loss can negatively impact long-term health outcomes and increase frailty. Understanding the specific impact of these popular pharmacotherapies on LBM is essential for optimizing treatment strategies and patient counseling. This meta-analysis addresses the gap in quantifying LBM changes.

This systematic review and meta-analysis searched PubMed, MEDLINE, Cochrane Library, and CINAHL up to October 2022. It included 36 randomized controlled trials (RCTs) involving patients with obesity, type 1 diabetes mellitus, type 2 diabetes mellitus, or polycystic ovary syndrome. Studies compared GLP-1RAs or SGLT2 inhibitors against placebo or active comparators. The primary outcome was the change in lean body mass (LBM), assessed using various body composition measurement techniques.

The meta-analysis of 36 studies revealed a consistent loss of lean body mass (LBM) with both drug classes. > GLP-1 receptor agonists were associated with a mean LBM loss of -1.51 kg (95% CI: -2.00 to -1.01). SGLT2 inhibitors resulted in a mean LBM loss of -1.04 kg (95% CI: -1.45 to -0.64). Subgroup analyses, stratified by body composition outcome type, measurement technique, and disease status, showed largely consistent results, indicating the robustness of this finding across different patient populations and assessment methods. Importantly, these effects were not modified by sex. Further analysis quantified that lean mass accounted for 28% (95% CI: 22%-34%) of the overall weight loss induced by both GLP-1RA and SGLT2i therapies. This suggests that a substantial portion of the weight reduction achieved with these agents is attributable to LBM loss.