Diabetes drugs may reduce cardiovascular deaths

Drugs originally developed for the treatment of Type 2 diabetes may benefit patients with heart failure, according to a new study from Harvard-affiliated Brigham and Women’s Hospital.

Scientists from BWH, in collaboration with a team from University of Glasgow, presented research from the largest trial to date of heart failure patients with mildly reduced or preserved ejection fraction. (Ejection fraction is a measurement of how much blood is ejected from the heart as it contracts.) The study was published in The New England Journal of Medicine and The Lancet.

Researchers found that dapagliflozin, which had previously been shown to benefit patients with heart failure with reduced ejection fraction, is likely to also reduce cardiovascular deaths and hospitalization for patients with mildly reduced or preserved ejection fraction. Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitor — a class of drugs that causes the body to excrete sugar in urine. In addition to controlling blood sugar in patients with diabetes, SGLT-2 inhibitors have been shown to provide significant cardiovascular and kidney disease benefits.

“There are more than 64 million people worldwide affected by heart failure, half of whom have mildly reduced or preserved ejection fraction,” said Scott Solomon of BWH’s Division of Cardiovascular Medicine, who presented results from the DELIVER trial, a randomized, placebo-controlled trial of dapagliflozin, funded by AstraZeneca.

“These findings establish SGLT2 inhibitors as foundational treatment for patients living with heart failure, regardless of ejection fraction, to help prevent hospitalization and morbidity and to extend meaningful survival and improve health-related quality of life, said Solomon. “These are the outcomes that matter most to patients and to clinicians — to keep patients feeling well and living longer.”

Muthiah Vaduganathan, also of BWH’s Division of Cardiovascular Medicine, presented results from a pre-specified meta-analysis of DELIVER and EMPEROR-Preserved, a large-scale clinical trial of empagliflozin, funded by Boehringer Ingelheim and Eli Lilly.

“Our meta-analysis, encompassing more than 12,000 patients, provides a summary of the totality of the evidence and drives home the message that, when it comes to heart failure, this is a therapy for all,” said Vaduganathan. “These trials included patients across a broad range of ages, race, functional class, sex, and medical histories, but regardless of individual characteristics, they benefited consistently from this treatment.”

Vaduganathan and colleagues further incorporated data from additional clinical trials with SGLT2 inhibitors, including those performed with dapagliflozin and empagliflozin in patients with reduced ejection fraction, and in patients from a clinical trial of the SGLT1/2 inhibitor sotagliflozin. The totality of the evidence with all these data suggest that patients across the full spectrum of heart failure benefit from this class of drugs, irrespective of ejection fraction or care setting.

The authors note that the work has some limitations. Less than 5 percent of patients enrolled in DELIVER were Black, the COVID pandemic limited symptom assessment after March 2020, and subgroups in the trial were underpowered. However, findings were consistent across prespecified subgroups.

Disclosures: Disclosure forms provided by the authors are available with the full text of the published paper at NEJM.org. Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi; received speaker fees from AstraZeneca, Novartis, and Roche Diagnostics; and participates on clinical trial committees for studies sponsored by Galmed, Novartis, Bayer, Occlutech, and Impulse Dynamics.

DELIVER funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.