Meta-Analysis Details Cardiovascular, Kidney Benefits of SGLT2 Inhibitors

A meta-analysis of 6 of the most impactful outcome trials concerning sodium-glucose cotransporter 2 (SGLT2) inhibitors in recent years is detailing the cardiovascular and renal benefits seen across the class in patients with type 2 diabetes.

Results of the study, which aggregated data from more than 45k unique patients, found SGLT2 inhibitors were associated with reduced risk of adverse cardiovascular disease events and kidney outcomes and noted significant heterogeneity when examining associations of various agents within the class on cardiovascular death.

“The present results augment the growing evidence base that SGLT2 inhibitors in general are associated with favorable CV and kidney outcomes; in addition, the present study refines understanding of important differences in outcomes associated with drugs within the class,” wrote study investigators.

With data from within the class being released at a pace that makes it nearly impossible for practicing clinicians to stay up-to-date, a team of clinicians and trial investigators sought to define the benefits of the class seen from major outcomes trials. To do so, investigators performed a systematic literate search of the PubMed database for randomized, placebo-controlled cardiovascular and kidney outcomes trial of SGLT2 inhibitors in patients with type 2 diabetes published between January 1, 2015-January 31, 2020.

In total, 145 studies were initially identified by investigators. After application of inclusion criteria, investigators were left with a cohort of 6 trials for the final analysis. These 6 trials included by the investigators were EMPA-REG OUTCOME, CANVAS, CANVAS-R, DECLARE-TIMI 58, CREDENCE, and VERTIS CV. From these 6 trials, investigators obtained information related to 46,969 patients, including 66.2% with prevalent ASCVD. This patient population had a mean age of 63.7 (7.9) years, 65.9% were men, 78.5% were white, and the mean follow-up time was 2.4-4.2 years.

For the purpose of the analysis, outcomes of interest for the current study included the composite of major adverse cardiovascular events of myocardial infarction, stroke, or cardiovascular death, and each individual component, the composite of hospitalization for heart failure or cardiovascular death, and each individual component, and kidney composite outcomes.

Upon analysis, results indicated SGLT2 inhibitors were associated with a reduced risk of major adverse cardiovascular events (HR, 0.90; 95% CI, 0.85-0.95; P=.27), hospitalizations for heart failure or cardiovascular death (HR, 0.78; 95% CI, 0.73-0.84; Q statistic, P=.09) and kidney outcomes (HR, 0.62; 95% CI, 0.56-0.0.70; Q statistic, P=.09)—with investigators noting no significant heterogeneity of associations with outcomes.

Results suggested the associated risk reduction for hospitalizations for heart failure (HR, 0.68; 95% CI, 0.61-0.76; I²=0.0%) was consistent across trials, while significant heterogeneity of associations with outcome was observed for cardiovascular death (HR, 0.85; 95% CI, 0.78-0.93; Q statistic, P=.02; I²=64.3%).

Further analysis revealed the present or absence of atherosclerotic cardiovascular disease did not modify the association with outcomes for major adverse cardiovascular events and noted similar absence of association with outcome modification for hospitalization for heart failure/cardiovascular death(P for interaction=.63), hospitalization for heart failure (P for interaction=.26), or kidney outcomes (P for interaction=.73).

“Although the mechanisms underpinning the CV and kidney outcomes of SGLT2 inhibitors remain uncertain, it is clear that the benefits are not attributable to glucose control per se,” wrote investigators.

This study, “Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis,” was published in JAMA Cardiology.​