SGLT2 inhibitors carry no excess risk of amputation

Neither canagliflozin nor other sodium glucose co-transporter-2 (SGLT2) inhibitors contribute to an increased risk of amputation among patients with diabetes mellitus, as reported in a recent study.

Researchers performed a systematic review and meta-analysis of randomized controlled trials evaluating the risk of amputation in relation to the use of SGLT2 inhibitors vs non-SGLT2 inhibitors or placebo in patients with diabetes.

The meta-analysis included five trials involving a total of 39,067 patients with diabetes mellitus, among whom 21,395 were on SGLT2 inhibitors. The proportion of those who had had limb amputation varied between 0.36 percent and 3.18 percent in the SGLT2 group and between 0 percent and 2.87 percent in the control group. Follow-up duration ranged from 24 weeks to 4.2 years.

Pooled data showed no significant difference in the risk of amputation among patients in the SGLT2 and control groups (odds ratio, 1.31, 95 percent confidence interval [CI], 0.92–1.87; I², 75 percent). Results for the subgroup analysis were consistent, indicating that canagliflozin, empagliflozin, and dapagliflozin did not contribute to a risk increase.

Assessed using the Cochrane tool, the risk of bias among the studies was low because they reported adequate random sequence generation and allocation concealment.

However, the researchers highlighted a need for additional studies, as types of amputations could be heterogeneous and the results may be skewed.