SGLT2 Inhibitors and Amputation Risk

A meta-analysis of 15 randomized controlled trials of SGLT2 inhibitors for diabetes and non-diabetes patients, conducted in Singapore, showed no significant difference in amputation risk for the various SGLT2 inhibitors versus placebo.

The findings, published in Pharmacology, will be helpful for physicians in assessing amputation risk when initiating treatment with SGLT2 inhibitors in patients with diabetes.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are being increasingly used for the treatment of diabetes mellitus as well as therapeutic extra-glycemic effects. However, there have been concerns for its use over complications including amputation events, given the results from the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial. Amputations are one of the major diabetes complications related to high morbidity and mortality.

To clarify the association between the two, See R.M., National University of Singapore, Singapore, and colleagues, therefore, conducted a systematic review and meta-analysis of randomized-controlled trials to investigate the effect of SGLT2 inhibitors on amputation events.

For this purpose, the researchers searched the online databases for studies that examined the effect of SGLT2 inhibitors on amputation events. A total of 15 randomized controlled trials were included with a combined cohort of 63,716 patients.

The researchers found no significant difference in amputation events across different types of SGLT2 inhibitors, different baseline populations, and different duration of SGLT2 inhibitor use.

To conclude, patients treated with SGLT2 inhibitors did not have any significant difference in amputation events compared to placebo across various subgroup analyses conducted. The use of canagliflozin, however, led to higher amputation events in certain trials.

"There have been numerous trials showing insignificant results, and a clear association between SGLT2 inhibitors and amputation events has not been established," the authors wrote. "This study will aid physicians in assessing the risk of amputations when initiating treatment with SGLT2 inhibitors."

Reference

The study titled, "Effects of Sodium-Glucose Cotransporter 2 on Amputation Events: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials," was published in the journal Pharmacology.

DOI: https://doi.org/10.1159/000520903