ATLANTA, Georgia—Study reveals how semaglutide helps the heart, showing patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes experience reduced symptoms and physical limitations after one year of treatment was found to have improved significantly. The STEP-HFpEF DM trial showed that semaglutide led to less weight loss than non-diabetic patients.

The findings, presented at the American College of Cardiology’s 2024 Scientific Sessions, add to speculation that glucagon-like peptide-1 (GLP-1) inhibitors may have cardiovascular effects beyond weight loss. It will inevitably increase.

“I think what we saw is very interesting,” lead researcher Mikhail Kosyborod, MD, of St. Luke’s Mid-America Heart Institute in Kansas City, Missouri, told TCTMD. “The magnitude of benefit was very similar to that observed in the original STEP-HFpEF trial in people without diabetes.”

of Step-HFpEF The study showed positive changes in C-reactive protein (CRP) and NT-proBNP with weekly semaglutide, supporting the idea that it was more effective than weight loss (Wegovy; Novo Nordisk ). These results were not entirely unexpected considering: select Trial data shows that when added to standard care in overweight or obese adults without diabetes, the risk of serious adverse cardiovascular events is reduced by 20%.

Knowing that diabetic patients typically lose about 40% less weight with GLP-1 receptor agonists than non-diabetic patients, Dr. Kosiborod said, “There are differences in treatment efficacy based on weight severity.” If we believed it was possible, we needed the STEP-HFpEF DM trial.” Unfortunately, it is undesirable to include these patients in the same trial. ”

In a study published at the same time, New England Medical JournalPatients who received semaglutide had a greater mean change from baseline in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and a greater mean change in body weight compared to patients who received placebo. . A larger increase was also seen within a 6-minute walk.

“This is a very important message for this field. Of course, losing weight is important. That is one of the factors behind what we are observing,” Kosiborod pointed out. “But this trial clearly suggests that weight loss is not everything.” [and] Semaglutide likely has disease-modifying benefits that are independent of weight loss. ”

STEP-HFpEF DM results

In this study, 616 HFpEF patients (median age 69 years, 44% female) were randomized to weekly semaglutide starting at the lowest dose (0.25 mg for 4 weeks) and by week 16. The dose was increased to the maintenance dose (2.4 mg). Or a placebo. The median body mass index (BMI) was 36.9, with 64% of participants having a BMI of 35 or higher, and the median duration of diabetes was 8 years. In addition to diuretics, renin-angiotensin system blockers, and beta-blockers, about one-third of patients were also taking mineralocorticoid receptor antagonists and sodium-glucose cotransporter 2 inhibitors.

Approximately 15% of patients in each group discontinued study treatment prematurely. By the end of the study period, 80% of patients assigned semaglutide were still taking weekly maintenance doses.

This trial clearly suggests that weight loss isn’t everything. Mikhail Kosivolod

The mean change in KCCQ-CSS at week 52 was 13.7 points in the semaglutide group and 6.4 points in the placebo group. The weight change rates were 9.8% and 3.4%, respectively (P < 0.001 for both comparisons).

The 6-minute walk test showed an increase in height of 12.7 meters in the semaglutide group and a decrease in height of 1.6 meters in the placebo group (P = 0.008).

Analysis of the stratified composite endpoint showed a higher stratified win rate for semaglutide than for placebo (1.58; 95% CI 1.29-1.94). This result is driven by a 15-point difference in the KCCQ-CSS and holds true for most major components of the hierarchical composite endpoint.

CRP levels were 42% lower in semaglutide patients compared to baseline at week 52, compared to a 12.8% decrease in the placebo group (P < 0.001). For NT-proBNP, the semaglutide group started at a median of 477.8 pg/mL, a change of 23.2%, compared with only a 4.6% change from baseline in the placebo group.

Hospitalization or HF-related emergency visit occurred in 7 patients in the semaglutide group compared with 18 patients in the placebo group (HR 0.40; 95% CI 0.15-0.92).

Serious adverse events and adverse events of special interest, such as hypoglycemia and diabetic retinopathy, occurred in 17.7% of semaglutide users compared to 28.8% of placebo users (P = 0.002). The rate of treatment discontinuation due to serious adverse events was 10.6% with semaglutide and 8.2% with placebo. 6.5% of discontinuations in the GLP-1 group were due to gastrointestinal adverse events common to these drugs.

strongly suggestive data

The benefits of semaglutide over KCCQ-CSS are “greater than any intervention studied in HFpEF to date,” Kosiborod told TCTMD.

In their paper, researchers hypothesize that the weight-loss-independent benefits of semaglutide in HFpEF “may include direct effects on decongestion.” Blood vessel, skeletal muscle, and mitochondrial function. Epicardial adipose tissue. Inflammation; that factor may be more pronounced in people with type 2 diabetes (unlike weight loss) than in people without type 2 diabetes. ”

Professor Kosiborod said the data was probably not enough to be completely conclusive, especially given the small numbers, but added: “The fact that we see the same signal in two independent trials in different patient populations “This very strongly suggests that the low number of cases is not a coincidence.” There were more events in the semaglutide group than in the placebo group. ”

What this means for patients like those in the study remains to be seen, but the data suggest that semaglutide treatment be studied for longer periods of time in this patient population to see if signs of improvement continue with treatment duration. This suggests there is a need, he added.

“Older adults, especially those with HFpEF, are the ones who typically present with the most debilitating symptoms, and are also the ones most concerned with improving their symptoms. [and in] It’s more about the quality of life than the quantity of life,” Kosiborod said. “There aren’t a lot of treatments for this type of heart failure. Very few have been proven to be effective. What these data really hope to do is encourage payers to increase coverage of obesity drugs. It makes us reconsider our stance.”

Additional data will come from the pooled analysis of STEP-HFpEF and STEP-HFpEF DM and will be presented here tomorrow. This analysis is expected to provide further insight into the benefits and tolerance of semaglutide across subgroups.