Risk of lower extremity amputations in people with type 2 diabetes mellitus treated with sodium-glucose co-transporter-2 inhibitors in the USA: A retrospective cohort study

AimsTo examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 (SGLT2) inhibitors overall, and canagliflozin specifically, compared with non-SGLT2 inhibitor antihyperglycaemic agents (AHAs). Materials and MethodsPatients with T2DM newly exposed to SGLT2 inhibitors or non-SGLT2 inhibitor AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2 inhibitors, canagliflozin, or non-SGLT2 inhibitor AHAs. Patients newly exposed to canagliflozin and non-SGLT2 inhibitor AHAs were matched 1:1 on propensity scores, and a Cox proportional hazards model was used for comparative analysis. Negative controls (outcomes not believed to be associated with any AHA) were used to calibrate P values. ResultsBetween April 1, 2013 and October 31, 2016, 118018 new users of SGLT2 inhibitors, including 73024 of canagliflozin, and 226623 new users of non-SGLT2 inhibitor AHAs were identified. The crude incidence rates of BKLE amputation were 1.22, 1.26 and 1.87 events per 1000 person-years with SGLT2 inhibitors, canagliflozin and non-SGLT2 inhibitor AHAs, respectively. For the comparative analysis, 63845 new users of canagliflozin were matched with 63845 new users of non-SGLT2 inhibitor AHAs, resulting in well-balanced baseline covariates. The incidence rates of BKLE amputation were 1.18 and 1.12 events per 1000 person-years with canagliflozin and non-SGLT2 inhibitor AHAs, respectively; the hazard ratio was 0.98 (95% confidence interval 0.68-1.41; P=.92, calibrated P=.95). ConclusionsThis real-world study observed no evidence of increased risk of BKLE amputation for new users of canagliflozin compared with non-SGLT2 inhibitor AHAs in a broad population of patients with T2DM.