Study finds SGLT-2 inhibitors linked to lower risk of diabetic foot nerve damage

A large population-based study found that adults with type 2 diabetes (T2D) who start treatment with sodium–glucose cotransporter-2 (SGLT-2) inhibitors have a slightly lower risk of developing diabetic foot problems compared to those taking glucagon-like peptide-1 (GLP-1) receptor agonists. The difference, which appeared after 3 years, was mainly due to fewer cases of nerve damage in the feet among SGLT-2 inhibitor users. The study is published in Annals of Internal Medicine.

Researchers from Aarhus University and Aarhus University Hospital and colleagues analyzed national health care registry data from more than 84,000 Danish adults with T2D who began treatment with either SGLT-2 inhibitors or GLP-1 receptor agonists between 2013 and 2023 to compare the risk of diabetic foot disease. Over 6 years, 10.8% of SGLT-2 users developed foot disease compared to 12% of GLP-1 users, a modest difference driven mainly by reduced nerve damage among SGLT-2 users.

Rates of leg ulcers, amputations, problems with leg arteries, and mortality were very similar in both groups. Additional analyses suggested that frequent medication discontinuation, treatment crossover, and potential differences in outcome surveillance could have influenced the results, making it uncertain if there was truly any difference between the two drugs.

The authors say these findings add to the growing evidence that both SGLT-2 inhibitors and GLP-1 receptor agonists offer additional benefits beyond blood sugar control and may help guide treatment decisions for patients at risk for diabetic foot disease.

Reference:

Frederik P.B. Kristensen, Diana H. Christensen, Brian C. Callaghan, et al. Effectiveness of Sodium–Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists on Diabetic Foot Disease: An Emulated Target Trial. Ann Intern Med. [Epub 6 January 2026]. doi:10.7326/ANNALS-25-01262