SGLT2 Inhibitors Reduce Hospitalizations for Heart Failure, Regardless of Type 2 Diabetes

Roy Rasalam, MBBS

New evidence of sodium-glucose cotransporter 2 inhibitors (SGLT2i) show an evolution toward improved outcomes with heart failure (HF) and chronic kidney disease (CKD) in patients both with and without type 2 diabetes (T2D).

A recent study, led by Roy Rasalam, MBBS, College of Medicine & Dentistry, James Cook University, reviewed randomized controlled trials to assess the effects of SGLT2 inhibitors on hospitalization for heart failure (HHF) and cardiac function.

They found that SGLT2is reduced HHF in patients with established HF with reduced ejection fraction (HFrEF) and CKD, regardless of type 2 diabetes status.

Methods

Investigators included RCT studies on the effectiveness of SGLT2i compared with placebo on HHF events.

They also investigated the effects of SGLT2is compared with placebo on cardiac structure and function as primary outcomes.

Further, the team included RCTs assessing broader potential mechanisms of SGLT2i efficacy in HF.

In assessments of HHF, they collected event rate data, hazard ratios, 95% confidence intervals, and P values for the effect of SGLT2i in comparison with placebo.

In addition, investigators extracted data for mean changes from baseline in primary outcomes, relevant summary statistics and P values for SGLT2is in comparison with placebo for trials assessing cardiac structure and function.

Information on study design and patient characteristics, as well as a risk of bias (RoB) assessment approach were included in the review.

Results

Investigators noted that all studies assessing the impact of SGLT2is compared with placebo on HHF were deemed to have a low RoB.

Data show SGLT2 inhibitors were consistent in reducing HHF risk across trial populations versus placebo (27% - 39%).

Investigators noted the results of the DAPA-HF and EMPEROR-Reduced trials showed the same benefit in patients with HFrEF, regardless of T2D status and showing SGLT2i as active treatment of HFrEF.

The DAPA-HF trial showed treatment with dapagliflozin significantly reduced the risk of the primary outcome by 26% compared with placebo, with the exploratory endpoint of HHF reduced by 30%.

Further, identical results were collected with empagliflozin treatment in the EMPEROR-Reduced trial at 25% and 31% for the primary endpoint and HHF.

Investigators found 5 trials with 56 - 105 patients with a low RoB who assessed the effects of 6 - 12 months of SGLT2i treatment with 4 trials reporting significant improvement compared to placebo.

Another 5 trials with low RoB assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels showed significant reductions after 8 - 12 months (3730 - 4744 patients) but not ≤12 weeks (80 - 263 patients).

The team noted that limited RCT-derived evidence suggested various cardioprotective SGLT2i mechanisms, including improved hemodynamics and vascular function, enhanced erythropoiesis, and reduced tissue sodium.

Conclusion

Investigators concluded SGLT2is reduced HHF rates in clinical trials, both in patients with HFrEF and CKD, regardless of T2D status.

They noted they likely to also be effective in patients with heart failure with preserved ejection fraction (HFpEF).

They noted that upcoming trial data will further clarify efficacy and mechanistic profiles of SGLT2is.

“Further research into SGLT2i mechanisms will offer new insights into the pathophysiological mechanisms contributing to disease progression in HF, and the nuanced functions of the kidney, potentially yielding novel drug targets for both CKD and HF,” investigators wrote.

The study, “Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review,” was published online in the European Society of Cardiology.