No significant increase in amputation risk with SGLT2 inhibitors in real-world study
medwireNews: Patients with type 2 diabetes who are treated with sodium-glucose cotransporter (SGLT)2 inhibitors have numerically higher rates of amputation than those given dipeptidyl peptidase (DPP)-4 inhibitors, but the difference does not reach statistical significance, researchers report.
In 2016, the US FDA “issued a safety alert regarding amputations associated with canagliflozin,” which was “based on a two-fold increase in risk reported in the Canagliflozin Cardiovascular Assessment Study (CANVAS) program,” say Glen Schumock (University of Illinois at Chicago, USA) and study co-authors.
However, they note that this increased risk for amputations “was not observed in non-CANVAS trials of canagliflozin or in trials with other agents in this class, dapagliflozin and empagliflozin,” and recently reported results from the OBSERVE-4D real-world study found no evidence to support an elevated risk for below the knee amputation with canagliflozin.
In their current study, Schumock and colleagues used data from a US commercial database to compare amputation rates among 30,216 adult patients who initiated SGLT2 inhibitor treatment between 2013 and 2015, and the same number of patients who initiated DPP-4 inhibitors. Patients were matched on the basis of high dimensional propensity scores accounting for factors including age, sex, time of treatment initiation, and presence of diabetic foot injuries.
Over a median follow-up of approximately 7 months, 36 patients taking SGLT2 inhibitors and 24 patients in the DPP-4 inhibitor group underwent any amputation, most commonly partial foot amputation, giving corresponding incidence rates of 1.62 and 1.15 per 1000 person–years.
Although the incidence of amputation was numerically higher among SGLT2 inhibitor-treated patients, at a hazard ratio of 1.38, the difference did not reach statistical significance, report the researchers in Diabetes, Obesity and Metabolism.
In subgroup analyses, the team found that “risk differed by type” of SGLT2 inhibitor. Compared with DPP-4 inhibitors, dapagliflozin and empagliflozin were associated with a higher risk for amputation than canagliflozin was, but the difference in amputation risk between any of the individual SGLT2 inhibitors and DPP-4 inhibitors did not reach statistical significance.
“While our finding was not statistically significant, it does not rule out a potential for harm,” say Schumock and colleagues, who call for additional well-designed observational studies on amputation risk associated with SGLT2 inhibitors.
“Findings from multiple such studies can then be synthesized in meta-analyses to clarify this ongoing concern to providers and patients with diabetes and inform decision making in clinical practice,” they conclude.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group