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Research shows that semaglutide significantly improves heart failure symptoms in both males and females and aids weight loss. Iuliia Burmistrova/Getty Images
  • Semaglutide is commonly used to treat type 2 diabetes and aid weight loss, but scientists are also exploring how this GLP-1 receptor agonist can treat other health conditions, including heart failure.
  • A recent study reported that semaglutide reduces the need for and dose of loop diuretics in people with heart failure with preserved ejection fraction (HFpEF).
  • A secondary analysis of these findings discovered that semaglutide significantly improves heart failure symptoms in both males and females, leading to greater weight loss in the latter.

With the recent popularity of glucagon-like peptide-1 (GLP-1) receptor agonists for treating type 2 diabetes and weight loss, scientists are examining the treatment possibilities of this class of medications for other conditions.

These include sleep apnea, high blood pressure, nonalcoholic fatty liver disease, polycystic ovary syndrome (PCOS), Alzheimer’s disease, and cardiovascular diseases such as stroke and heart failure.

For instance, a recent study found that semaglutide — the active ingredient in Ozempic and Wegovy — may help reduce symptoms of heart failure with preserved ejection fraction (HFpEF) in people with obesity and type 2 diabetes.

A recent study from the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program reports that semaglutide reduces the need for and dose of loop diuretics in people with HFpEF. These findings were presented May 11–14 at Heart Failure 2024, a scientific congress of the European Society of Cardiology (ESC).

The scientists found that semaglutide had a positive impact on the symptoms, physical limitations, and body weight of people with HFpEF regardless of their use of diuretics.

Now, a secondary analysis of the STEP-HFpEF findings discovered that semaglutide significantly improves heart failure symptoms in both men and women with a common type of heart failure that has few therapeutic options.

Although women in the study lost more weight than men, both groups experienced near-equal heart failure symptom improvement, suggesting semaglutide’s heart failure benefits could be independent of weight loss.

This study pooled data from two trials — “Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity” published in August 2023, and “Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes” published in March 2024 — for a combined 1,145 study participants with an average age of 70.

In both trials, participants had obesity-related HFpEF and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) of less than 90. This questionnaire assesses the quality of life of people with heart failure.

Study participants randomly received either semaglutide or a placebo for 52 weeks. Participants were divided into those not receiving diuretics, a subset receiving non-loop diuretics only, and a subset receiving loop diuretics.

After analyzing the pooled data, researchers found that participants who took semaglutide improved their KCCQ-CSS regardless of whether they were taking diuretics or not. However, the improvement was greater in participants receiving loop diuretics compared to those not taking them.

In those taking semaglutide and receiving loop diuretics, their loop diuretics dose decreased by 17% after 52 weeks.

“Diuretics can help with fluid overload, but they don’t necessarily target the underlying mechanisms behind HFpEF,” Rigved Tadwalkar, MD, a board certified consultative cardiologist at Providence Saint John’s Health Center in Santa Monica, CA — not involved in this study — told Medical News Today.

“To see the diuretic data that these individuals can potentially reduce their diuretic dose, they need to escalate their diuretic dose less, and they just have a lesser need to have diuretics at all once they’re treated with semaglutide is excellent because it moves their care forward.”

Scientists found that semaglutide helped participants lose weight during the 52 weeks.

Participants not taking diuretics lost an average of 8.8% of their starting weight. The participants in the highest loop diuretic dose category lost 6.9% of their body weight on average.

“Semaglutide improved symptoms, physical limitations, and led to greater weight loss across diuretic use categories in patients with HFpEF,” study author Kavita Sharma, MD, associate professor of medicine in Advanced Heart Failure/Transplant Cardiology in the Division of Cardiology at Johns Hopkins University School of Medicine and director of the Johns Hopkins Heart Failure with Preserved Ejection Fraction Program, said in a news release.

“There was evidence of a significant reduction in average loop diuretic dose, a lower likelihood of diuretic treatment escalation, and a greater likelihood of diuretic treatment de-escalation with semaglutide versus placebo — parameters that indicate disease-modifying effects of semaglutide, and are associated with better long-term clinical outcomes in this patient population.”

— Kavita Sharma, MD, study author

In this secondary analysis of the STEP-HFpEF program data, researchers found that both male and female participants experienced notable improvements in heart failure symptoms, physical limitations, and exercise.

In terms of weight loss, scientists reported female participants lost an average of 9.6% of their body weight, compared to male participants who lost an average of 7.2%.

However, despite the weight loss difference, researchers found both genders experienced similar heart failure symptom benefits, suggesting semaglutide’s effect on heart failure may be independent of weight loss.

“Understanding the sex differences in obesity-related HFpEF is of great importance,” Mikhail Kosiborod, MD, a cardiologist at Saint Luke’s Mid-America Heart Institute in Kansas City, Missouri, and senior author of the study said in a news release.

“Obesity and visceral adiposity are key drivers of HFpEF development and progression, and this may be even more amplified in women, who represent the majority of people with the disease, and bear a heavier burden of symptoms and physical limitations due to HFpEF. Our study sheds light on these differences and the consistent benefits of semaglutide for women and men.”

Heart failure occurs when the heart is pumping abnormally and it cannot support the circulation demanded by the body.

HFpEF is a specific type of heart failure in which the heart muscles stiffen and cannot properly fill with blood. In HFpEF, the left ventricle of the heart cannot relax and fill with blood as it normally should.

“Heart failure with preserved ejection fraction … involves a stiffening of the heart muscle over time, and it’s much more common than people understand,” Tadwalkar explained.

“In this particular situation, the heart function remains normal. It’s just the stiffness of the heart that can lead to a backup of fluid into the body and cause symptoms similar to the standard or heart failure with reduced ejection fraction patient, which includes fatigue, shortness of breath, body swelling, (and) leg swelling.”

Current treatment options for people with HFpEF include medications such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and loop diuretics. These help remove excess fluid buildup to achieve healthy blood volume in the body, medically known as euvolemia.

As past research has shown that about 84% of HFpEF is caused by overweight or obeity, lifestyle changes such as reduced salt intake, increased physical activity, and weight loss can also assist with HFpEF.

After reviewing the original research released in May 2024, Mir Ali, MD, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, told MNT it was not surprising that semaglutide medications where people lose weight would improve heart conditions, such as heart failure.

“We’ve seen this in our surgical patients as well — as they lose weight a lot of these things improve,” Ali continued.

“I think this will broaden the indications for use of these medications that may not just be for diabetes or weight, but maybe for heart-related conditions, such as heart failure or coronary artery disease, that there may be some benefit to these medications,” he said.

“What would be interesting to see is if this effect is independent of weight loss. So if they could somehow structure a study that compares patients on these types of medications and their need for diuretics versus patients on other medications and similar weight loss (and) compare their use of diuretics to see if there’s a benefit that’s independent of the weight loss.”

— Mir Ali, MD, bariatric surgeon

Tadwalkar noted he would like to see additional studies looking at even bigger endpoints.

“The big endpoints of heart failure are frequency of hospitalization or a rate of re-hospitalization, and then, of course, mortality — are people living longer because of this?” he continued.

“Anything that we can do to move that needle forward for these HFpEF patients is of high importance — we need to look at those endpoints in another trial or other studies,” Tadwalkar concluded.