Risk for Foot Disease Modestly Lower With SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists in T2DM

TUESDAY, Jan. 6, 2026 (HealthDay News) — For adults with type 2 diabetes mellitus (T2DM), new users of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have a modestly lower risk for foot disease compared with glucagon-like peptide-1 receptor agonist (GLP-1 RA) users, according to a study published online Jan. 6 in the Annals of Internal Medicine.

Frederik P.B. Kristensen, M.D., Ph.D., from Aarhus University in Denmark, and colleagues compared the risks for foot disease in new users of SGLT-2is and GLP-1 RAs in a cohort study using target trial emulation. Using national health care registry data, adults with T2DM initiating SGLT-2i or GLP-1 RA treatment were identified from 2013 to 2023. The registry cohort included 53,769 and 30,380 new users of SGLT-2is and GLP-1 RAs, respectively.

The researchers found that any foot disease occurred in 10.8 and 12.0 percent of SGLT-2i and GLP-1 RA users, respectively, during six years of follow-up, corresponding to a risk ratio of 0.90 in an intention-to-treat analysis. Differences were not apparent until after year 3, when 40 and 32 percent of SGLT-2i and GLP-1 RA users, respectively, had discontinued initial treatment. Lower risk for neuropathy drove the modest reduction in risk among SGLT-2i users (risk ratio, 0.78). Similar risks for peripheral artery disease, foot ulcers, amputations, and all-cause mortality were seen for users of SGLT-2is and GLP-1 RAs.

“The absolute differences were small, and whether this difference reflects a causal effect of the initial medication used is uncertain,” the authors write.

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