While new research observed lowered incidence of hospitalization for heart failure in patients taking sodium glucose co-transporter 2 (SGLT2) inhibitors such as canagliflozin, the study team also identified fewer downsides than previously suggested.

In fact, research published in Diabetes, Obesity & Metabolism identified no significant association between those medication and below-knee lower extremity amputation.

SGLT2 inhibitors. Source

Industry researchers noted that some SGLT2 inhibitors, which are indicated for treatment of type 2 diabetes mellitus (T2DM, have reported cardiovascular benefit. In addition, studies of the drug class also have reported elevated risk of below‐knee lower extremity (BKLE) amputation.

Data from 4 large U.S. administrative claims databases were used to gauge the real‐world comparative effectiveness within the SGLT2i class and compared with non‐SGLT2i antihyperglycemic agents. Specifically, the research focused on risk and provided population‐level estimates of canagliflozin's effects on hospitalization for heart failure (HHF) and BKLE amputation vs other SGLT2i and non‐SGLT2i in T2DM patients.

The 4 databases included 142,800 new users of canagliflozin, 110,897 new users of other SGLT2i and 460, 885 new users of non‐SGLT2i. The meta‐analytic hazard ratio estimate for HHF with canagliflozin vs. non‐SGLT2i was 0.39 (95% CI, 0.26‐0.60) in the on‐treatment analysis.

As for BKLE amputation with canagliflozin vs. non‐SGLT2i, the hazard ratio was 0.75 (95% CI, 0.40‐1.41) in the on‐treatment analysis and 1.01 (95% CI, 0.93‐1.10) in the intent‐to‐treat analysis.

Noting that effects in the subpopulation with established cardiovascular disease were similar for both outcomes, researchers emphasized that no consistent differences were observed between canagliflozin and other SGLT2i.

“In this large comprehensive analysis, canagliflozin and other SGLT2i demonstrated HHF benefits consistent with clinical trial data, but showed no increased risk of BKLE amputation vs non‐SGLT2i,” study authors concluded. “HHF and BKLE amputation results were similar in the subpopulation with established cardiovascular disease. This study helps further characterize the potential benefits and harms of SGLT2i in routine clinical practice to complement evidence from clinical trials and prior observational studies.”

The BKLE results were backed up by another study from University of Illinois at Chicago researchers.  The report in Diabetes, Obesity & Metabolism confirmed that, while all SGLT2i had a risk for amputations, it did not reach statistical significance, in a comparison with dipeptidyl peptidase-4 inhibitors (DPP4i). The authors further reported that the rates were lowest with canagliflozin compared to other drugs in the class.