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  • People with type 2 diabetes and a certain type of heart failure saw improvements in their symptoms after 1 year of semaglutide injections, a new study shows.
  • While participants receiving semaglutide lost less weight than people without diabetes in an earlier trial, they saw similar benefits.
  • This suggests the heart failure-related benefits of semaglutide may extend beyond those due to weight loss, say researchers.

People with type 2 diabetes and a certain type of heart failure saw improvements in their symptoms and physical limitations after 1 year of semaglutide injections, new research shows.

These benefits occurred even though this group of patients lost less weight than people without diabetes in a similar trial.

Semaglutide is the active ingredient in Novo Nordisk’s diabetes drug Ozempic and weight-loss drug Wegovy. Last month, the Food and Drug Administration (FDA) also approved Wegovy for reducing the risk of serious heart problems in people who are overweight or have obesity.

The findings suggest that semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, may offer heart-related benefits beyond those stemming from weight loss.

“This is an important trial which reinforces the concept that patients with the syndrome of heart failure can benefit further from administration of a drug that was originally developed to reduce blood sugar, and has now emerged as an important way to reduce cardiovascular and heart failure events,” said Richard Wright, MD, cardiologist at Providence Saint John’s Health Center in Santa Monica, Calif., who was not involved in the new research.

The findings were presented Apr. 6 at the American College of Cardiology 2024 Scientific Session in Atlanta, and simultaneously published in the New England Journal of Medicine.

The new study included 616 people with heart failure with preserved ejection fraction (HFpEF), which is a form of heart failure that occurs when the heart is unable to relax properly between each heartbeat, but can pump at a normal output, or ejection fraction. All participants also had obesity and type 2 diabetes.

Participants were randomly assigned to receive either once-weekly semaglutide injections or an inactive placebo. People in the semaglutide group started at the lowest dose, which was then increased to a maintenance dose by week 16.

After following participants for a year, researchers found that people in the semaglutide group lost more weight and had larger reductions in symptoms related to heart failure, compared to those in the placebo group.

This included greater improvements in their quality of life and daily functioning, and being able to walk further on a 6-minute walking test.

These kinds of physical improvements would allow people to more easily walk to a neighbor’s house or to a nearby grocery store, said Andrew Choi, MD, associate professor of medicine and radiology at the George Washington University School of Medicine and Health Sciences, who was not involved in the research.

Yu-Ming Ni, MD, a cardiologist and lipidologist at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, Calif., pointed out that a lack of mobility and physical activity can contribute to symptoms of heart failure, something that can be worsened by obesity.

“We have known for many years that structured exercise improves heart failure outcomes,” said Ni, who was not involved in the new study. “So it doesn’t surprise me that this medication, with its impact on weight loss, can contribute to a reduction in heart failure symptoms.”

However, while weight loss played a big part in the reduction in people’s symptoms, Ni said the drug may contribute in other ways, such as by reducing inflammation, which was suggested by some of the changes in biomarkers seen in the study.

This included large reductions in C-reactive protein (CRP) and NT-proBNP levels among people receiving semaglutide. CRP levels are related to inflammation and can be an indicator of your risk of developing cardiovascular problems. NT-proBNP is a measure of the severity of heart failure and may be elevated in heart failure with preserved ejection fraction (HFpEF).

The researchers agreed, writing that the findings “suggest that the mechanisms of benefit with semaglutide may extend beyond weight loss.” This may be due to the effects of the drug on the heart and blood vessels, inflammation, insulin resistance and other factors, they said.

While people receiving semaglutide lost weight, as was expected, the weight reduction was 40% lower than what was seen by people with heart failure but not diabetes in an earlier trial.

Choi said this lower weight loss in patients with diabetes is expected. Other glucose-lowering drugs that patients were taking — such as insulin or sodium-glucose co-transporter 2 (SGLT2) inhibitors — may “blunt” the weight loss effects of semaglutide, he told Healthline.

Wright said the study “raises the important issue as to whether administration of a GLP-1 receptor agonist would have similar benefits in those individuals with heart failure but without obesity or diabetes.” This would need to be studied in future clinical trials.

The average age of participants in the study was 69 years and almost half were women. Almost two-thirds had a body mass index (BMI) of 35 or higher, with people having diabetes for 8 years on average.

In addition to diuretics, most participants were receiving other standard treatments, including renin-angiotensin system blockers and beta-blockers. Some were also on mineralocorticoid receptor antagonists and SGLT2 inhibitors.

Approximately 15% of people in each group discontinued the study treatment early. In addition, 80% of the people in the semaglutide group who finished the trial were still on the weekly maintenance dose.

In the placebo group, 18 patients were hospitalized or had an urgent visit related to heart failure, compared to seven patients in the semaglutide group.

Certain adverse events occurred less often in the semaglutide group, including hypoglycemia and diabetic retinopathy. These are both complications of type 2 diabetes.

Overall, 10.6% of participants in the semaglutide group stopped treatment early due to an adverse event, while 8.2% in the placebo group did. This included gastrointestinal disorders, which are a known side effect of GLP-1s.

The study has some limitations, including the small number of participants and that researchers only followed people for one year. More study will be needed to verify the findings.

However, “[the study] findings strongly support that a GLP-1 receptor agonist, such as semaglutide, should now be considered an important ‘fifth pillar’ of pharmacologic treatment of patients with heart failure and obesity,” Wright told Healthline, “even for those already on conventional pharmacologic treatments.”

Although Ni agrees that weight loss can improve functioning and quality of life in people with heart failure, he questions whether a drug like semaglutide should be recommended for all patients with this condition.

“I’m constantly telling my patients that weight loss can help with heart failure symptoms, but it doesn’t have to be with a medication,” he told Healthline. “A lot of my focus is on healthy lifestyle — exercise, diet and natural weight loss — as a means to improve heart failure outcomes.”

Choi emphasized that while the use of semaglutide is growing, the medication should be used only for approved indications, which currently includes weight loss, treatment of diabetes and reducing heart-related risks in certain people.

“In addition, strict adherence to a heart-healthy diet, regular exercise and gradual dose titration [of semaglutide] is important to avoid negative side effects,” he said.

Researchers recruited over 600 people with heart failure with preserved ejection fraction (HFpEF), obesity and type 2 diabetes. They randomly assigned people to receive weekly injections of semaglutide (Wegovy) or an inactive placebo.

After one year, people who had received semaglutide had greater improvements in quality of life and physical functioning, in addition to reductions in key biomarkers related to heart function. People also experienced fewer exacerbations requiring a doctor’s visit or hospitalization.

People with heart failure and type 2 diabetes lost less weight on semaglutide compared to those in an earlier trial without diabetes. This, say researchers, suggests that semaglutide offers heart-related benefits beyond those involving weight loss.