Effect of SGLT2 Inhibitors on Heart Failure-Related Hospitalization, Below-Knee Amputation

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New users of canagliflozin had significantly less risk of hospitalization for heart failure than new users of non-SGLT2 inhibitors.
New users of canagliflozin had significantly less risk of hospitalization for heart failure than new users of non-SGLT2 inhibitors.

While there is an observed lowered incidence of hospitalization for heart failure in patients taking sodium glucose co-transporter 2 (SGLT2) inhibitors like canagliflozin, there is no association with these medicines to below-knee lower extremity amputation, according to research published in Diabetes, Obesity & Metabolism.

Study researchers sought to examine and compare the drugs in the SGLT2 inhibitor class (canagliflozin, empagliflozin, dapagliflozin, empagliflozin, and dapagliflozin) and non-SGLT2 inhibitors to investigate the drugs' effects on hospitalizations for heart failure and below-the-knee amputations.

Using a population-level, retrospective comparative cohort design, researchers examined more than 700,000 records from 4 observational databases for this clinical trial study, which was approved and reviewed by the FDA. Participation were classified as being new users of canagliflozin (n=142,800), new users of other SGLT2 inhibitors (n=110,897), and new users of non-SGLT2 inhibitors (n=460,885).

New users of canagliflozin had significantly less risk of hospitalization for heart failure than new users of non-SGLT2 inhibitors (on-treatment meta-analytic hazard ratio 0.39; 95% confidence interval, 0.26-0.60). There was no difference observed in hospitalization for heart failure when comparing canagliflozin to other SGLT2 inhibitors. In addition, there was no association with any SGLT2 inhibitor and increased risk for below-knee lower extremity amputation. Lastly, no consistent differences between canagliflozin and other SGLT2 inhibitors were observed.

Study limitations include the potential for mistakes that would confound and misclassify data. Investigators also noted that a weakness in the research is that record validation was not performed, making it possible that differential bias affected results.

Study investigators note that “canagliflozin has a profile similar to other [SGLT2 inhibitors] as used in routine clinical practice. Patients and providers may find this information useful when weighing the comparative benefits against the potential risks in making treatment decisions to support diabetes care.”

This study was supported by Janssen Research & Development, LLC.

Reference

Ryan PB, Buse JB, Schuemie MJ, et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: a real-world meta-analysis of 4 observational databases (OBSERVE-4D) [published online June 25, 2018]. Diabetes Obes Metab. doi: 10.1111/dom.13424

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