Wegovy helps HFpEF patients with diabetes

ATLANTA — The weight loss and heart failure benefits of semaglutide (Wegovy) extend to patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes, the STEP-HFpEF DM trial showed.

As measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, 2.4 mg of a GLP-1 receptor agonist improved HF-related symptoms and physical limitations compared to 1-year change with placebo (on a 100-point scale). (13.7 to 6.4 points on a perfect score). Points KCCQ-CSS scale, P<0.001).

Patients also lost 6.4 percentage points in weight over that period with semaglutide (-9.8% vs. -3.4%; P<0.001), Mikhail N. Kosyborod, MD, St. Luke's Mid-America Heart Institute and University of Missouri-Kansas City School of Medicine, reported at the American College of Cardiology Annual Meeting. The survey results were also published in the following articles: New England Medical Journal.

This result mirrored that of the similarly designed STEP-HFpEF trial in a population without type 2 diabetes. A combined analysis of the two trials was also presented at the conference; lancetthere was a 7.5 percentage point greater change in KCCQ-CSS and an 8.4 percentage point greater weight loss from baseline to week 52 (both) compared to placebo. P<0.0001).

Overall, the research group concluded that regarding obesity-related HFpEF, “the concordant results of the two trials provide greater evidence that semaglutide is an effective treatment option with a good safety profile in a wide range of populations.” It gives a sense of security,” he concluded.

what it means

Of note, KCCQ-CSS improvements were similar between the two trials, even though diabetic patients lost approximately 40% less weight.

Session commentator Lee R. Goldberg, MD, MPH, of the University of Pennsylvania in Philadelphia, noted that the approximately 10% weight loss with semaglutide was still expected.

Kosivolod’s group pointed to the use of insulin and insulin secretagogues as a potential reason for slower weight loss in the diabetic group, but noted that “the mechanism of benefit with semaglutide extends beyond weight loss and directly affects weight loss.” It also suggests that there may be a negative impact.” Factors such as decongestion, vascular, skeletal muscle, and mitochondrial function, epicardial adipose tissue, inflammation, and insulin resistance are more pronounced in people with type 2 diabetes than in people without type 2 diabetes (unlike weight loss). There may be. ”

However, this difference between trials demonstrated that the heart failure effect was independent of weight loss, Erwan Donal, MD, of the University of Rennes, France, and colleagues write in an accompanying document. . comment in Lancet.

“Semaglutide represents a major step forward in addressing key unmet needs in this vulnerable population, particularly in terms of improving motor function and quality of life,” the researchers wrote.

Although SGLT2 inhibitors are the only disease-modifying therapy for HFpEF, the researchers say this finding also has implications for semaglutide in the majority of patients (approximately 80% of HFpEF patients are overweight or obese). He claimed that there was. “Taken together, these results provide a signal of potential reduction in clinical events and require further confirmation in heart failure outcome trials,” the researchers wrote.

A further question, Donal’s group noted, is what happens with combined treatment of SGLT2 inhibitors and GLP1 receptor agonists. Subgroup analysis showed a consistent effect of semaglutide on HF-related outcomes with or without the use of SGLT2 inhibitors.

Trial details

STEP-HFpEF DM included 616 adults with type 2 diabetes who had heart failure with preserved ejection fraction (left ventricular ejection fraction ≥45%), BMI ≥30, and hemoglobin A1c ≤10%. It was included. The patient also had to have at least one higher risk characteristic. that is, either elevated left ventricular filling pressures, elevated natriuretic peptide levels and abnormal echocardiography, or heart failure hospitalization and abnormal echocardiography or continued treatment with diuretics within the past 12 months.

Participants were randomly assigned to receive weekly semaglutide for 52 weeks (dose increased to 2.4 mg over 16 weeks) or placebo. Median age was 69 years, 44.3% female, and median BMI was 36.9.

KCCQ-CSS and weight loss were common primary endpoints.

Among the confirmatory secondary endpoints, the change in 6-minute walk distance from baseline to week 52 was an increase of 12.7 meters in the semaglutide group compared to a decrease of 1.6 meters in the placebo group (P=0.008). For the stratified composite endpoint of all-cause mortality, heart failure events, KCCQ-CSS, and reaching 6-minute walk distance threshold, the “win” rate was higher for semaglutide than for placebo (1.58, 95% CI 1.29 -1.94, P<0.001).

The trial also confirmed safety in patients with type 2 diabetes, who “have unique potential vulnerabilities,” with an overall reduction in serious adverse events (AEs) (17.7% vs. 28.8%). P=0.002) and fewer cardiac events (19 vs. 40; P=0.004), with numerically fewer discontinuations due to serious AEs (1.9% vs. 3.6%).

“Semaglutide reduced glycated hemoglobin levels without increasing clinically significant hypoglycemia (even though baseline blood glucose was well controlled),” the researchers noted. . “Additionally, we did not see an increase in diabetic retinopathy events with semaglutide, which is a potential concern for GLP-1 receptor agonists in type 2 diabetes.”

Goldberg noted that one of the limitations is generalizability. She noted the relatively low proportion of women compared to the typical proportion of HFpEF cases, as well as the small proportion of black participants (4.2% in the semaglutide group and 1.6% in the placebo group).

Kosivolod responded by pointing out that while the U.S. enrolls 26% of patients, black populations are smaller in other countries.