The effect of SGLT2 inhibitors in patients with heart failure and type 2 diabetes

By Bhavana KunkalikarJun 21 2023Reviewed by Danielle Ellis, B.Sc.

In a recent study published in the European Heart Journal, researchers assessed the impact of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors on type 2 diabetes and heart failure (HF) patients in real-world clinical settings.

Background

In 2015, a randomized controlled trial was conducted to study the effects of an SGLT2 inhibitor on HF-related outcomes in type 2 diabetes patients. This trial, known as EMAP-REG Outcome, found that empagliflozin, an SGLT2 inhibitor, led to a significant reduction in the 3-point major adverse cardiovascular events (3-MACE) along with an early decrease in HF hospitalization (HHF) in comparison to the placebo.

Trials have been conducted on HF patients with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), or those with and without diabetes. SGLT2 inhibitors have since become a crucial aspect of foundational therapy for HF patients, irrespective of their left ventricular ejection fraction.

About the study

A total of 59,605 patients with both type 2 diabetes and HF were enrolled using Medicare claim data spanning between April 2013 and December 2019. The study analyzed the efficacy of SGLT2 inhibitors in comparison to sitagliptin, a dipeptidyl-peptidase 4 (DPP4) inhibitor, and explored variations among SGLT2 inhibitors for HFrEF or HFpEF. The research involved 16,253 individuals who initiated SGLT2 inhibitors and 43,352 individuals who initiated sitagliptin. The primary endpoint was a combination of all-cause mortality and deteriorating HF over a 365-day follow-up period.

Results

The study found that initiating SGLT 2 inhibitors reduced risk with a hazard ratio (HR) of 0.72 compared to sitagliptin for the primary composite endpoint. The adjusted relative risk reduction noted for all-cause mortality was 30% with an HR of 0.70, 36% for HFF with an HR of 0.64, and 23% for urgent visits requiring i.v. diuretics with an HR of 0.77. The study found no variation among the three SGLT2 inhibitors, namely dapagliflozin, empagliflozin, or canagliflozin, with respect to their impact on HF with preserved or reduced ejection fraction.

The authors discovered that patients treated with SGLT2 inhibitors experienced a significant decrease in HFF as early as day five of follow-up, consistent with the early benefits observed in randomized controlled trials. The population in the study was approximately ten years older compared to the population in the corresponding cardiovascular outcome trials (CVOTs). This finding is significant since most CVOTs do not adequately represent individuals aged 70 years and above, despite this population having a prevalence of type 2 diabetes exceeding 20%.

Conclusion

The data support the findings of previous studies on SGLT2 inhibitors, including randomized controlled trials and meta-analyses. The results show similar estimates for heart failure hospitalization, reinforcing the effectiveness of these inhibitors for individuals at high risk. This study confirms that patients with HF and type 2 diabetes should be administered SGLT2 inhibitors to decrease heart failure-related endpoints, regardless of their ejection fraction.

The evidence supports using SGLT2 inhibitors to improve HF-related outcomes in HF patients with type 2 diabetes. Implementing this treatment in clinical practice is important to reduce the risk of complications and death in this vulnerable group.