SGLT2 Inhibitors Demonstrate Effectiveness for Primary, Secondary Heart Failure

Investigators found that sodium-glucose contrasporter-2 (SGLT2) inhibitors demonstrated effectiveness for the primary and secondary prevention of heart failure (HF) across a broad range of care settings and patient populations.

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The results of a review, published in Cureus, showed that the SGLT2 inhibitors reduced the risk of HF, regardless of HF or type 2 diabetes (T2D) status. It was also generally safe with no major safety concerns evident, though there was a slightly increased risk of euglycemic ketoacidosis and genitourinary infections. The inhibitors were generally well tolerated.

The medication was also useful in both and HF with preserved ejection fraction (HFpEF) HF with reduced ejection fraction (HFrEF), regardless of diabetes status.

Investigators called for further randomized controlled trials to explore the efficacy and safety of the SGLT2 inhibitors.

They included 13 studies in the literature review, using a search of Cochrane Library, Google Scholar, Medline, PubMed, and other databases. Keywords included cangliflozin, cardiovascular and renal outcome with SGLT2 inhibitors, dapagliflozin, empagliflozin, ertugliflozine, heart failure, HFpEF, HFrEF, sotagliflozin, and type 2 diabetes.

Investigators limited the inclusion to randomized control trials published in English between 2012 and 2022.

There were 8 studies that included SGLT2 inhibitors for the primary prevention of HF and 5 on the secondary prevention.

The studies for the primary prevention of HF included: CANVAS PROGRAM (NCT01032629); CREDENCE (NCT02065791); Dapa-CKD (NCT03036150); DECLARE-TIMI58 (NCT01730534); EMPA-KIDNEY (NCT03594110), EMPA-REG OUTCOME (NCT01131676); SCORED (NCT03315143); and VERTIS-CV (NCT01986881).

Investigators found that canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin reduced major adverse cardiac events, with dapagliflozin also reducing cardiovascular (CV) death and hypertensive HF (HHF).

Additionally, canagliflozin and dapagliflozin reduced the composite outcome of renal events. Empagliflozin also reduced the initial occurrence of renal deterioration or CV deaths.

Sotagliflozin reduced the cumulative deaths from CV disease, HHF, and the need for HF visits.

For the secondary prevention of HF, studies that investigators used included DAPA-HF (NCT03036124), DELIVER (NCT03619213), EMPEROR PRESERVED (NCT03057951); EMPEROR REDUCED (NCT03057977); and SOLOIST HF (NCT03521934).

Investigators found that dapagliflozin reduced the combination of worsening of HF and CV death and the worsening of CV in 2 separate studies. Empagliflozin reduced the combination of HHF and CV death in 2 studies, while sotagliflozin reduced the sum of CV deaths, HHD, and urgent HR visits.

The data also showed that the drugs had an acceptable risk-benefit profile and were generally safe and well tolerated. The most common adverse events reported was increased risk of genitourinary infection, which included genital mycotic and urinary tract infections.

Most of the data from the studies comparing individuals with/without T2D came from a subgroup analysis, so it could have affected the outcomes of the review, investigators said, adding that 2 other major trials, 1 for dapagliflozin and 1 for empagliflozin, could give more insight.

The results of the review could help determine which patents would benefit from SGLT2 inhibitors for the prevention of HF, investigators.

Reference

Wahinya M, Khan Z. Sodium-glucose contrasporter-2 (SGLT2) inhibitor therapy for the primary and secondary prevention of heart failure on patients with and without type 2 diabetes mellitus: a systemic review. Cureus. 15(4): e37388. doi:10.7759/cureus.37388