Effects of canagliflozin on amputation risk in type 2 diabetes: the CANVAS Program

作者：David R. Matthews, Qiang Li, Vlado Perkovic, Kenneth W. Mahaffey, Dick de Zeeuw, Greg Fulcher, Mehul Desai, William R. Hiatt, Mark R. Nehler, Elisa Fabbrini, Mary Kavalam, Mary Lee, Bruce Neal · 发表于：Diabetologia · 年份：2019 · DOI：10.1007/s00125-019-4839-8 · 被引用次数：130 · 研究领域：Diabetes Treatment and Management、Bariatric Surgery and Outcomes、Pancreatic function and diabetes

AIMS/HYPOTHESIS: The primary analysis of the Canagliflozin cardioVascular Assessment Study (CANVAS) Program showed canagliflozin to have a beneficial effect on cardiovascular and renal outcomes in people with type 2 diabetes at high cardiovascular risk, but also an unexpected increased risk of major or minor lower extremity amputation. These secondary analyses explore this finding in more detail. METHODS: The effect of canagliflozin on amputation risk in the CANVAS Program was calculated for amputations of different types and proximate aetiologies and different canagliflozin doses. Univariate and multivariate associations of baseline characteristics with amputation risk were determined and proportional and absolute effects of canagliflozin were compared across subgroups. RESULTS: There were 187 (1.8%) participants with atraumatic lower extremity amputations (minor 71%, major 29%); as previously published, rates were 6.30 vs 3.37 per 1000 participant-years with canagliflozin vs placebo (HR 1.97 [95% CI 1.41, 2.75]). Risk was similar for ischaemic and infective aetiologies and for 100 mg and 300 mg doses. Overall amputation risk was strongly associated with baseline history of prior amputation (major or minor) (HR 21.31 [95% CI 15.40, 29.49]) and other established risk factors. No interactions between randomised treatment and participant characteristics explained the effect of canagliflozin on amputation risk. For every clinical subgroup studied, numbers of amputation events pr...