Clinical Report: SGLT-2is Edge GLP-1 RAs on Foot Disease

Overview

Revise to emphasize the clinical significance of the 1% difference in foot disease risk.

Background

Diabetic foot disease is a significant complication of type 2 diabetes, leading to increased morbidity and healthcare costs. Understanding the comparative risks associated with different diabetes medications is crucial for optimizing patient outcomes. This study provides insights into the long-term risks of foot disease associated with SGLT-2 inhibitors and GLP-1 receptor agonists.

Data Highlights

Key Findings

• SGLT-2i users had a 6-year risk of peripheral neuropathy of 4% compared to 5% for GLP-1 RA users.
• At 6 years, the discontinuation rate was higher for SGLT-2i users (52%) compared to GLP-1 RA users (44%).
• In a per-protocol analysis, SGLT-2i users showed a higher risk of foot ulcers and lower-limb amputation.
• Surveillance differences may have introduced detection bias, particularly for neuropathy outcomes.
• After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups.

Clinical Implications

Clinicians should consider the differential risks of diabetic foot disease when prescribing SGLT-2 inhibitors versus GLP-1 receptor agonists. The findings suggest that SGLT-2 inhibitors may offer a protective effect against peripheral neuropathy, which is a critical consideration in long-term diabetes management.

Conclusion

Highlight the need for further research addressing detection bias and limitations.

References

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2. The New Gastroenterologist — GLP-1s Increase GERD Risk Over SGLT2 Inhibitors in T2D
3. retinal physician — The Effect of GLP-1RAs in Diabetic Retinopathy
4. JAMA Network Open — GLP-1 Receptor Agonists or SGLT2 Inhibitors and Nonarteritic Anterior Ischemic Optic Neuropathy
5. the ophthalmologist — Wegovy and Possible Vision Risk
6. GLP-1s Increase GERD Risk Over SGLT2 Inhibitors in T2D
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9. FDA removes Boxed Warning about risk of leg and foot amputations for canagliflozin
10. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2025
11. SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists and Risk of Diabetic Foot Disease in Denmark | Consultant360