Endocrinol Metab.  2019 Sep;34(3):247-262. 10.3803/EnM.2019.34.3.247.

A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans

  • 1Diabetes Research Centre, University of Leicester, Leicester, UK. melanie.davies@uhl-tr.nhs.uk
  • 2NIHR Leicester Biomedical Research Centre, University Hospital of Leicester NHS Trust and the University of Leicester, Leicester, UK.
  • 3National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK.
  • 4NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC), Leicester, UK.


Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.


Glucagon-like peptide-1 receptor agonists; Sodium-glucose cotransporter 2 inhibitors; Diabetes mellitus, type 2; Weight loss; Body composition; Lean body mass

MeSH Terms

Bariatric Surgery
Body Composition
Body Weight
Diabetes Mellitus, Type 2
Glucagon-Like Peptide 1*
Glucagon-Like Peptide-1 Receptor*
Muscle, Skeletal
Population Characteristics
Weight Loss
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
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