The CANVAS Programme demonstrated that canagliflozin reduced major adverse cardiovascular events by 14% in patients with type 2 diabetes at high cardiovascular risk, but identified an approximately twofold increase in lower-extremity amputation risk, primarily at the toe or metatarsal level, requiring careful patient selection and monitoring.
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The EMPA-REG OUTCOME trial demonstrated that empagliflozin reduced cardiovascular death by 38% and heart failure hospitalisation by 35% in patients with type 2 diabetes and established cardiovascular disease — the first glucose-lowering agent to show a mortality benefit in a cardiovascular outcomes trial.