Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk
Abstract
Numerous studies have established that patients with type 2 diabetes mellitus are at heightened risk of ischemic cardiovascular events, including myocardial infarction and stroke, and microvascular events, including nephropathy and retinopathy. 1Treatments to lower glucose concentrations have demonstrated consistent benefits for reducing microvascular complications regardless of mechanism.Establishing the link between glucose lowering and reducing cardiovascular risk has been more challenging, particularly over the durations of most clinical trials.3][4] The SGLT2i appear to have particularly profound benefits in patients with established cardiovascular disease for reducing cardiovascular death and heart failure as well as adverse renal outcomes.Benefits have been reported in 2 completed randomized trials with consistent associations in observational studies, 2-5 including those reported by Udell et al 6 in this issue of Circulation.In contrast to the more consistent cardiovascular benefits described across these studies, however, is a finding isolated to the CANVAS trial (Canagliflozin Cardiovascular Assessment Study) showing an excess risk of amputation with canagliflozin. 4 These divergent signals of harm in the limb coupled with general cardiovascular benefit have raised questions, including whether the observation is a result of chance alone as well as the potential mechanisms of harm.[9][10] In this context, the results from Udell et al 6 provide the greatest impact.In…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 25 participants or records.
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