SGLT-2 Inhibitors May Increase Amputation Risk

Treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors may be associated with an increased risk of amputation in patients with type 2 diabetes, according to the results of a recent study.

Previous studies have suggested that canagliflozin, an SGLT-2 inhibitor, could be associated with a decreased risk of extremity amputation.

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To examine this relationship further, as well as the effects of SGLT-2 inhibitors and other oral medication for type 2 diabetes on 4 other outcomes (peripheral arterial disease, critical limb ischemia, osteomyelitis, and ulcer), researchers conducted a retrospective cohort study of 953,906 commercially insured individuals from Truven Health MarketScan Commercial Claims and Encounters data.

Sensitivity analyses were used to assess the effects of combining dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists as a single referent group, adjust for baseline use of older oral agents, and include people with baseline amputation.

Overall, 39,869 new users of SGLT-2 inhibitors (4.2%), 105,023 new users of DPP-4 inhibitors (11.0%), and 39,120 new users of GLP-1 agonists (4.1%) were identified.

Following propensity score weighting and adjustment for demongraphics, severity of diabetes, comorbidities, and medication, a nonstatistically significant increased risk of amputation was observed with new use of SGLT-2 inhibitors compared with DPP-4 inhibitors (adjusted hazard ratio [HR] 1.50) and GLP-1 agonists (HR 1.47). Further, new use of SGLT-2 inhibitors was statistically significantly associated with amputation compared with sulfonylureas, metformin, or thiazolidinediones (HR 2.12).

“Use of SGLT-2 inhibitors may be associated with increased risk of amputation compared with some oral treatments for type 2 diabetes. Further observational studies are needed with extended follow-up and larger sample sizes.”

—Michael Potts

Reference:

Chang H, Singh S, Mansour O, et al. Association between sodium-glucose cotransporter 2 inhibitors and lower extremity amputation among patients with type 2 diabetes [Published online August 13, 2018] JAMA Intern Med. doi:10.1001/jamainternmed.2018.3034