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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

Jobanputra R, Sargeant JA, Plekhanova T, James E, Almaqhawi A, Webb DR, Davies MJ, Yates T

Diabetes/metabolism research and reviews, 2026

20 participants · 1 citation

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…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 20 participants or records.

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