The Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Co-Transporter-2 Inhibitors on Lean Body Mass in Humans: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Aims

The use of pharmacotherapies with weight loss properties for the management of obesity and chronic disease are now routinely prescribed. We investigated the evidence from randomised-controlled trials for the effects on lean body mass of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) in humans.

Materials and Methods

PubMed, MEDLINE, the Cochrane Library and CINAHL were searched from inception to October 2022. The primary outcome was change in body composition focused on measures of lean body mass (LBM).

Results

Thirty-six studies in population groups with obesity (n = 8), type 2 diabetes mellitus (n = 20), type 1 diabetes mellitus (n = 5) and polycystic ovary syndrome (n = 3) receiving a GLP-1RA or SGLT2i therapy versus placebo or active comparator satisfied our inclusion criteria, including 21 for GLP-1RA and 15 for SGLT2i. Meta-analysis showed an overall loss of LBM in the direction of the intervention groups prescribed GLP-1RA (MD: −1.51 kg [95% CI: −2.00 to −1.01]) and SGLT2i (MD: −1.04 kg [95% CI: −1.45 to −0.64]) with sub-group analysis showing largely consistent results when stratified by type of body composition outcome, type of body composition measurement technique and disease status. Results were not modified by sex. Further meta-analysis found that lean mass accounted for 28% (95% CI: 22%–34%) of overall weight loss induced by GLP-1RA and SGLT2i.

Conclusions

GLP-1RA and SGLT2i are associated with a loss of LBM that appears congruent with overall weight loss. Monitoring of body composition and provision of combined therapy to preserve lean mass during weight loss should be considered.