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

AIMS: To 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 METHODS: Patients 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. RESULTS: Between April 1, 2013 and October 31, 2016, 118 018 new users of SGLT2 inhibitors, including 73 024 of canagliflozin, and 226 623 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, 63 845 new users of canagliflozin were matched with 63 845 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). CONCLUSIONS: This 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.