A meta‐analysis of randomized controlled studies examining the effects of sodium‐glucose co‐transporter‐2 inhibitors on peripheral artery disease and risk of amputations

Abstract Aim Sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) are used to maintain glycaemic control as well as for their beneficial cardiovascular and renal effects in diabetes patients. However, increased risk of amputation and peripheral artery disease (PAD) have been observed with the use of some SGLT‐2is. A meta‐analysis was conducted to understand the effect of SGLT‐2is on amputation and PAD events using data from randomized controlled trials (RCT). Materials and Methods A systematic literature review was conducted using Medline and Central databases for RCTs that involved the administration of SGLT‐2is versus placebo/active comparators to diabetic patients. The primary outcome was amputation events and PAD. A random‐effects model was used to calculate the pooled odds ratio, and subgroup analyses was performed. Results A total of 51 RCTs were included in the meta‐analysis with data from 97 589 patients. Meta‐analysis of the data showed that there was a significant increase in PAD risk ( p = 0.04) but no significant increase in amputation risk with SGLT‐2i use versus placebo/active comparators ( p = 0.43). Subgroup analyses demonstrated no significant difference between SGLT‐2i type, duration of treatment or patient risk factors on amputation or PAD incidence. However, length of drug treatment (> 100 weeks) was associated with a significant increase in both PAD and amputation risks in the SGLT‐2i treatment groups. Conclusions The results of the meta‐analysis showed no significant association between SGLT‐2i use and PAD and amputation risks in diabetic patients when used for shorter treatment durations.