Do SGLT2 Inhibitors Raise the Risk of Lower Extremity Amputation?

Findings from a study published in Diabetes, Obesity and Metabolism reported no increased risk of below-knee lower extremity (BKLE) amputation for patients newly initiated on canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, vs. non-SGLT2 inhibitor antihyperglycemics in patients with type 2 diabetes mellitus. 

Using the Truven MarketScan database, researchers identified patients with type 2 diabetes that were newly started on SGLT2 inhibitors or non-SGLT2 inhibitor antihyperglycemic therapy. They examined the incidence of BKLE amputation for patients treated with SGLT2 inhibitors including canagliflozin and non-SGLT2 inhibitors. 

A total of 118,018 patients newly exposed to SGLT2 inhibitors (of which 73,024 were exposed to canagliflozin) and 226,623 patients newly exposed to non-SGLT2 inhibitors were included in the analysis. The incidence rate of BKLE amputation was 1.22 events per 1,000 person-years with SGLT2 inhibitors, 1.26 events per 1,000 person-years with canagliflozin, and 1.87 events per 1,000 person-years with non-SGLT2 inhibitors. 

In the comparative analysis that matched 63,845 new canagliflozin users with new non-SGLT2 inhibitor users, the incidence rate of BKLE amputation was 1.18 events per 1,000 person-years with canagliflozin vs. 1.12 events per 1,000 person-years with non-SGLT2 inhibitors (hazard ratio 0.98, 95% CI: 0.68–1.41; P=0.92).

Overall, the authors did not find evidence indicating an increased risk of BKLE amputation among new users of canagliflozin vs. non-SGLT2 inhibitors in a general population of patients with type 2 diabetes mellitus.

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