(267) Effect of Cardiovascular Disease and Diuretic Use on Amputation Risk with Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Type 2 Diabetes

Publication Number: 598

Background: Little is known on the effects of baseline cardiovascular disease or diuretic use on the risk of amputation associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors, especially in an Asian population that has a lower incidence of amputations than the Caucasian population.

Objectives: To investigate the risk of lower limb amputation associated with SGLT2 inhibitors among patients with type 2 diabetes according to the patient’s history of cardiovascular disease and diuretic use.

Methods: We conducted a new user, active-comparator cohort study using South Korea’s nationwide health insurance claims data from January 1, 2015 to December 31, 2020. The study cohort was patients with type 2 diabetes newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors, with cohort entry defined as the first date of the prescription. Within this cohort, we classified patients into four discrete subgroups based on their baseline status and conducted 1:1 propensity score matching between users of SGLT2 inhibitors and DPP4 inhibitors in each subgroup: cardiovascular disease and diuretic use (CVD+/DU+); cardiovascular disease only (CVD+/DU-); diuretic use only (CVD-/DU+); without cardiovascular disease and diuretic use (CVD-/DU-). We estimated incidence rates per 1000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression models for the risk of amputation associated with SGLT2 inhibitors versus DPP4 inhibitors.

Results: Among 1,588,797 patients in the study cohort (mean [SD] age, 60.2 [13.7] years; 42.3% women), we identified 219,900 patient-pairs of SGLT2 inhibitor and DPP4 inhibitor users after propensity score matching. The incidence rate per 1000 person-years in SGLT2 inhibitor and DPP4 inhibitor users in the four groups were: CVD+/DU+ group, 0.45 vs 1.21; CVD+/DU- group, 0.30 vs 0.64; CVD-/DU+ group, 0.31 vs 0.57; and CVD-/DU- group, 0.25 vs 0.51. The HRs for the risk of amputation associated with SGLT2 inhibitors versus DPP4 inhibitors were 0.36 (95% CI 0.14 to 0.90) for the CVD+/DU+ group, 0.46 (0.21 to 1.01) for the CVD+/DU- group, 0.55 (0.27 to 1.14) for the CVD-/DU+ group, and 0.49 (0.34 to 0.71) for the CVD-/DU- group.

Conclusions: History of cardiovascular disease and/or diuretic use appeared to have no effects on the risk of amputation associated with SGLT2 inhibitors among patients with type 2 diabetes. These results help clinicians to contextualize the risk of amputation with SGLT2 inhibitors in an Asian population in routine clinical practice.