Endocrinology

Bariatric surgery versus GLP-1RAs: much larger fat and lean mass losses, but both improve composition

In this 24-month retrospective cohort (n=3,066), bariatric surgery produced substantially greater fat mass reductions than semaglutide or tirzepatide. Adjusted fat mass reductions with surgery approached 50% by 12 months and were sustained at 24 months. GLP-1RA therapy yielded more modest fat mass reductions, remaining under 20% at 12–24 months. Lean mass losses were smaller than fat mass losses but still greater with surgery than with GLP-1RA treatment. Both strategies increased the fat-free mass to fat mass ratio, with surgical patients maintaining higher ratios throughout follow-up. 1

Umbrella review: GLP-1RAs show broad benefits but nontrivial adverse event signals and evidence gaps

This umbrella review synthesized 123 meta-analyses with 464 outcomes across metabolic, cardiovascular, renal, respiratory, cognitive, skeletal, and mortality domains. GLP-1RAs generally improved endocrine, cardiometabolic, renal, respiratory, and cognitive outcomes, with possible reductions in fracture risk and all-cause mortality in some settings. However, they were associated with higher risks of diabetic retinopathy, ketoacidosis, gastrointestinal events, and treatment discontinuation. Methodologic quality of many meta-analyses was limited, especially regarding search rigor, handling of bias, and reporting of exclusions. 2

After MI or stroke in type 2 diabetes, GLP-1RA use is rare but associated with sizable risk reductions

This Czech nationwide registry study evaluated GLP-1RA initiation within 12 months after nonfatal MI or ischemic stroke in patients with type 2 diabetes. Only about 2% of eligible MI and stroke survivors started a GLP-1RA despite guideline recommendations. In propensity-matched MI survivors, GLP-1RA use was associated with lower MACE risk and markedly reduced all-cause and cardiovascular mortality. Among stroke survivors with diabetes, GLP-1RA initiation similarly lowered MACE, all-cause death, and cardiovascular death. Women and older adults were less likely to receive GLP-1RAs, highlighting inequities in secondary prevention uptake. 3

SGLT2 inhibitors modestly reduce diabetic foot disease versus GLP-1RAs, mainly via less neuropathy

This Danish target-trial emulation compared new SGLT2 inhibitor users (n=53,769) with GLP-1RA users (n=30,380) for incident diabetic foot disease. Over six years, any foot disease occurred less often with SGLT2 inhibitors, with an intention-to-treat risk ratio of 0.90 versus GLP-1RAs. The difference was driven mainly by reduced peripheral neuropathy risk, with a risk ratio of 0.78. Risks of peripheral artery disease, foot ulcers, amputations, and all-cause mortality were similar between groups. Residual confounding and misclassification remain possible, but data support SGLT2i preference in patients at high neuropathic risk. 4