The effects of GLP-1 RAs compared to DPP4is or SGLT2is on appendicular lean mass index (ALMI): an interim analysis.

Abstract

Newer antihyperglycemic medications, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and Dipeptidyl peptidase-4 inhibitors (DPP4is), have grown in popularity for their blood glucose-lowering effects and cardiorenal benefits, as well as their support for weight loss efforts. However, the relationships between these medications and changes in lean and muscle mass, specifically appendicular lean mass index (ALMI) are not fully explored. This retrospective cohort study using population-based data identified 82 individuals who initiated one or more of these medications between two dual-energy x-ray absorptiometry (DXA) assessments. A previously described model was applied to regional spine and hip data from DXA assessments to estimate ALMI (eALMI). In the cohort, 54 (66%) initiated a DPP4i, 38 (46%) initiated an SGLT2i, and 6 (7%) initiated a GLP-1 RA. Mean change in eALMI between one and five years across all medications was -0.13 kg/m2 (SD 0.47). SGLT2is were associated with declining muscle mass, ranging from -0.31 kg/m2 (95% CI: -0.59, -0.04) to -0.82 kg/m2 (95% CI: -1.57, -0.07) after adjustments. There was no association with any medication class with a previously defined threshold for a large decline in eALMI of  -0.45 kg/m2, or any adverse clinical outcomes, including death, long-term care admission, or new home-care use. While SGLT2is were associated with a decline in eALMI, more research should be conducted to better understand this relationship, as well as ascertain if a relationship exists for DPP4i and GLP-1 RA medications.