Incretin‐based therapy and the risk of diabetic foot ulcers and related events
Nikki C. C. Werkman, Johanna H. M. Driessen, Olaf H. Klungel, Nicolaas S. Schaper, Patrick C. Souverein, Coen D.A. Stehouwer, Johannes T. H. Nielen
Abstract
AIM: To investigate the effect of dipeptidyl peptidase-4 inhibitors (DPP4-Is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) on diabetic foot ulcer (DFU) and DFU-related outcomes (lower limb amputation [LLA], DFU-related hospitalization and mortality). METHODS: We performed a cohort study with data from the Clinical Practice Research Datalink Aurum database with linkage to hospital data. We included people with type 2 diabetes starting treatment with metformin. Then we propensity score matched new users of DPP4-Is and sulphonylureas (N = 98 770), and new users of GLP1-RAs and insulin (N = 25 422). Cox proportional hazards models estimated the hazard ratios (HRs) for the outcomes. RESULTS: We observed a lower risk of DFU with both DPP4-I use versus sulphonylurea use (HR 0.88, 95% confidence interval [CI]: 0.79-0.97) and GLP1-RA use versus insulin use (HR 0.44, 95% CI: 0.32-0.60) for short-term exposure (≤ 400 days) and HR 0.74 (95% CI: 0.60-0.92) for long-term exposure (>400 days). Furthermore, the risks of hospitalization and mortality were lower with both DPP4-I use and GLP1-RA use. The risk of LLA was lower with GLP1-RA use. The results remained consistent across several sensitivity analyses. CONCLUSIONS: Incretin-based therapy was associated with a lower risk of DFU and DFU-related outcomes. This suggests benefits for the use of this treatment in people at risk of DFU.