Diabetes Obes Metab
Lower extremity amputation risk in patients with T2DM and PAD: How do T2DM meds stack up?
A systematic review and meta-analysis using evidence from large observational studies showed no statistically significant increase in risk of lower extremity amputation (LEA) for patients with T2DM and PAD prescribed SGLT2 inhibitors compared with GLP-1RAs.
Risk of LEA also appeared to be significantly lower in individuals with T2DM treated with SGLT2 inhibitors compared with DPP-4 inhibitors, and significantly higher with SGLT2 inhibitors compared with sulfonylureas.
Researchers undertook this study, in part, given recent safety concerns raised following the findings of the CANVAS (CANagliflozin cardioVascular Assessment Study) study. The CANVAS trial assessed the risk of CV outcomes in patients with T2DM and high CV risk. The study reported an increased risk of LEA for patients who received canagliflozin compared with placebo (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.41-2.75). This led to a product warning for canagliflozin from the European Medicines Agency and the FDA, and increased uncertainty as to the harms and benefits of prescribing canagliflozin in high-risk T2DM patients such as those with PAD, a history of amputation, neuropathy, or diabetic foot ulcers.
Given the potential beneficial effect of SGLT2 inhibitors on CV and diabetic outcomes, study authors note that these are important findings with possible implications for clinical practice.
Source:
Hodgson A, et al. (2024, April 1). Diabetes Obes Metabol. Risk of lower extremity amputation in patients with type 2 diabetes mellitus and peripheral arterial disease receiving sodium-glucose cotransporter-2 inhibitors versus other medications: A systematic review and meta-analysis of observational cohort studies. https://pubmed.ncbi.nlm.nih.gov/38558251/