A study compared the influence of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of lower extremity amputations in patients with type 2 diabetes. The results were published in Acta Diabetologica.

In this retrospective cohort study, researchers analyzed 2,939 new users (mean age, 64) of SGLT2i (empagliflozin, 59%; dapagliflozin, 41%) matched 1:1 to 2,939 new users of DPP-4i between June 2014 and June 2018. Exclusion criteria was defined as patients treated with insulin at baseline and patients with a history of amputation. Patients were matched in a 1:1 ratio using propensity score matching.

The results showed that the incidence of amputations was higher in SGLT2i than in DPP-4i users (4.2 vs. 2.7 per 1,000 patient years), yielding a hazard ratui (HR) of 1.58 (95% confidence interval [CI], 0.85-2.92; P = 0.145). An intention-to-treat analysis yielded to similar HR of 1.86 (95% CI: 1.10-3.14; P = 0.020), the researchers noted. There was no difference in amputation rates in the first two years; however, SGLT2i users had an almost a three-fold higher (95% CI: 1.63-4.84; P = 0.007) cumulative HR of amputation at four years compared with DPP-4i users.

“Compared with DPP-4i use, SGLT2i use did not result in a statistically significant higher overall risk of lower extremity amputations. However, the results suggest that SGLT2i may increase the risk of amputation with long-term use,” the researchers concluded.

Link: https://pubmed.ncbi.nlm.nih.gov/34609620/

Keywords: Amputation, Dipeptidyl peptidase-4 inhibitor, Sodium-glucose co-transporter 2 inhibitor, Type 2 diabetes