SGLT-2 Inhibitors Show Modest Advantage Over GLP-1 Receptor Agonists in Reducing Diabetic Foot Disease Risk

Diabetic foot disease is a serious complication for patients with type 2 diabetes, often leading to neuropathy, peripheral artery disease, foot ulcers, or even amputations. Recent research has explored whether sodium–glucose cotransporter-2 inhibitors, or SGLT-2 inhibitors, differ from glucagon-like peptide-1 receptor agonists, GLP-1RAs, in preventing these complications.

A Danish population-based study published in the Annals of Internal Medicine on January 6, 2026, examined new users of SGLT-2 inhibitors and GLP-1RAs from 2013 to 2023. Researchers used national health registry data along with a research cohort to compare the risk of diabetic foot disease outcomes. The study included 53,769 patients starting SGLT-2 inhibitors and 30,380 starting GLP-1 receptor agonists.

Key Findings

During six years of follow-up, 10.8% of patients using SGLT-2 inhibitors and 12.0% of those using GLP-1 receptor agonists developed some form of foot disease. This corresponds to a modestly lower risk for SGLT-2 inhibitor users. The difference was most noticeable after three years of treatment, as many patients discontinued initial therapy by that time.

The lower risk among SGLT-2 inhibitor users was primarily due to reduced incidence of neuropathy. Risks for peripheral artery disease, foot ulcers, lower-limb amputation, and all-cause mortality were similar between the two treatment groups.

Study Limitations

The authors noted potential limitations including residual confounding and the possibility of misclassifying exposure or outcomes. Despite these limitations, the study provides valuable insight for clinicians considering SGLT-2 inhibitors or GLP-1 receptor agonists for patients at risk of diabetic foot disease.

Conclusion

SGLT-2 inhibitors may offer a small advantage in reducing neuropathy-related foot disease among patients with type 2 diabetes compared to GLP-1 receptor agonists. Clinicians should weigh individual patient factors when deciding on treatment plans.

Source
Kristensen FPB, Christensen DH, Callaghan BC, et al. Effectiveness of Sodium–Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists on Diabetic Foot Disease. Ann Intern Med. 2026; Published online January 6.

Disclaimer
This blog is for informational purposes only and does not constitute medical advice. Patients should consult their healthcare provider before making any changes to medication or treatment plans.