SGLT2 Inhibitors Benefit All Patients with T2D, Regardless of CVD Diagnosis

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to cardiovascular benefits in all patients with type 2 diabetes (T2D), according to a study recently published in the Journal of the American Heart Association.

Previous study results have shown the drug class leads to a reduction in cardiovascular disease (CVD) events in patients with established atherosclerotic CVD, but results were unclear as to whether benefits translated to patients without CVD.

In this systematic review and meta-analysis, researchers analyzed data from 38,723 patients who participated in 4 trials. “We found SGLT2 inhibitors protected against cardiovascular disease and death in diverse subsets of patients with type 2 diabetes regardless of their cardiovascular disease history,” said Clare Arnott, PhD, a lead author of the study.

It is estimated that 370 million people worldwide are affected by T2D, and the presence of the disease is a major risk factor for CVD and chronic kidney disease. In addition, CVD is the leading cause of death in people with T2D.

Of the 38,723 patients included in the review, at baseline, 22,870 (59%) had CVD; 7754 (20%) had reduced kidney function, and 4543 (12%) had heart failure. Overall, 3828 major adverse cardiac events (MACEs) occurred in patients.

The researchers found, “There was no evidence of differences in the effects of SGLT2 inhibition in patients with or without CVD at baseline for any of the efficacy outcomes, except cardiovascular death, for which there was moderate evidence of greater protection with SGLT2 inhibition in those with CVD at baseline (HR, 0 .80; 95% CI, 0.71-0.90) compared with those without (HR, 0.95; 95% CI, 0.77-1.17; P = .167).”

One study included in the review, The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, boosted the review’s power. Because this trial enrolled large numbers of individuals at high risk of CVD but who did not have the disease at baseline, the researchers feel there is a strong case for the use of SGLT2 inhibitors in the primary prevention setting.

“Our results call for a reevaluation of current guideline recommendations for SGLT2 inhibitor therapy, with a view to include those with and without established CVD,” the authors said. They continued, “The overview findings support consideration of SGLT2 inhibition in primary, as well as secondary, prevention settings.”

The inclusion of diverse subsets in the review led the authors to conclude, “Available evidence does not identify clearly a patient group that is unlikely to achieve significant cardiovascular protection from use of this drug class.”

Reference

Arnott C, Li Q, Kang A, et al. Sodium-glucose cotransporter 2 inhibition for the prevention of cardiovascular events in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. J Am Heart Assoc. 2020;9(3):e014908. doi: 10.1161/JAHA.119.014908.