No increased risk of below-knee amputation with canagliflozin in real-world study
A real-world analysis on below-knee amputation of >700,000 US patients on canagliflozin compared to other SGLT2 inhibitors or anti-hyperglycemic medication was presented at June 24 at the American Diabetes Association’s® (ADA’s) 78th Scientific Sessions® in Orlando, FL, USA. Canagliflozin did not increase the risk of below-knee amputation in type 2 diabetes patients or patients with established CVD, but did reduce the risk of hospitalization for heart failure.
The CANVAS program showed that canagliflozin had positive effects on glycemic levels and CV benefit in patients with T2DM. However, increased risk of leg and foot amputation were observed with canagliflozin, and the Food and Drug Administration required a warning added to the drug label starting 2017.
US claims databases were used in the OBSERVE-4D study to evaluate the risk on amputation and hospitalization for HF with canagliflozin compared to other SGLT2i and anti-hyperglycemic therapies in a broad population of T2DM patients. This retrospective, real-world observational study included >700,00 patients (142,000 new users of canagliflozin, 110,000 users of other SGLT2i and 460,000 users of non-SGLT2i anti-hyperglycemic agents) with a median on-treatment period of <6 months.
No increased risk of lower limb amputation was observed with canagliflozin or any other SGLT2 and a reduction in hospitalization for heart failure was seen, consistent with randomized clinical trials and other studies. Further study is required as the number of patient with long-term exposure to canagliflozin was limited.
“Prior to this analysis, no real-world study has shown direct, head-to-head, comparative evidence among individual SGLT2i medicines,” said the study’s lead investigator John Buse, MD, PhD, director of the Diabetes Center, director of the North Carolina Translational and Clinical Sciences Institute and executive associate dean for clinical research at the University of North Carolina School of Medicine in Chapel Hill. Of course, when physicians evaluate the best treatment for their patients, they should consider the factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy and diabetic foot ulcers. Our research indicates that the overall benefit-risk profile of SGLT2i is positive, and physicians should feel comfortable and confident in prescribing the class to their patients.”