Semaglutide may improve heart failure symptoms and reduce the need for diuretics

Given the recent popularity of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes and weight loss, scientists are exploring the potential of this class of drugs 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 example, 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.

Now, a new study presented May 11-14 at Heart Failure 2024, a scientific congress of the European Society of Cardiology (ESC), reports that semaglutide reduces the need for and dosage of loop diuretics in people with HFpEF.

Scientists found that semaglutide had a positive effect on symptoms, physical limitations and body weight in people with HFpEF, regardless of their diuretic use.

Semaglutide reduces the dose of loop diuretics

This study combined 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, involving 1,145 participants with a median age of 70 years.

In both trials, participants had obesity-related HFpEF and a KCCQ-CSS score of less than 90, which assesses quality of life in people with heart failure.

Participants were randomly assigned to receive either semaglutide or placebo for 52 weeks. They were divided into those who received no diuretics, those who received only non-loop diuretics, and those who received loop diuretics.

Data analysis showed that participants taking semaglutide improved their KCCQ-CSS scores regardless of diuretic use, but the improvement was greater in those taking loop diuretics.

Those taking semaglutide and loop diuretics had a 17% reduction in diuretic dosage after 52 weeks.

"Diuretics can help with fluid overload, but they don't necessarily address the underlying mechanisms of HFpEF," said Dr. Rigved Tadwalkar, a board-certified cardiologist at Providence Saint John's Health Center in Santa Monica, California — who was not involved in the study.

"Seeing the data on diuretics that these people can potentially reduce their diuretic dose, they need less of an increase in their diuretic dose, and they just need less diuretics when they're on semaglutide is great because it moves their treatment forward."

Semaglutide Helps Lose Weight in HFpEF

Scientists found that semaglutide helped participants lose weight over 52 weeks.

Participants who did not take diuretics lost an average of 8.8% of their starting weight. Participants in the highest loop diuretic dose category lost an average of 6.9% of their weight.

"Semaglutide improved symptoms, physical limitations, and resulted in greater weight loss across different diuretic use categories in patients with HFpEF," said Dr. Kavita Sharma, study author and associate professor of medicine in the HFpEF Program at Johns Hopkins University School of Medicine.

"There was evidence of a significant reduction in the mean dose of loop diuretics, a lower likelihood of increasing the dose of diuretics, and a higher likelihood of decreasing the dose of diuretics with semaglutide compared with placebo - parameters that indicate a disease-modifying effect of semaglutide and are associated with better long-term clinical outcomes in this patient population."

What You Need to Know About HFpEF

Heart failure occurs when the heart pumps blood abnormally and cannot maintain the circulation needed by the body.

HFpEF is a specific type of heart failure in which the heart muscles become stiff and fail to fill with blood normally. In HFpEF, the left ventricle of the heart fails to relax and fill with blood as it should.

"Heart failure with preserved ejection fraction... involves hardening of the heart muscle over time, and it's much more common than people think," Tadwalkar explained.

"In this particular situation, the heart function remains normal. It's just that the stiffness of the heart can cause fluid retention in the body and cause symptoms similar to heart failure with reduced ejection fraction, which includes fatigue, shortness of breath, swelling of the body, and swelling of the legs."

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

As previous studies have shown, about 84% of HFpEF cases are caused by being overweight or obese, lifestyle changes such as reducing salt intake, increasing physical activity and losing weight can also help with HFpEF.

Potential expansion of indications for semaglutide

After reviewing the study, Dr. Mir Ali, a bariatric surgeon and medical director of the MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California, said it's not surprising that semaglutide-based drugs that help people lose weight improve heart conditions like heart failure.

"We've seen this in our surgical patients - as they lose weight, many of these problems improve," Ali continued.

"I think this will expand the indications for using these drugs, which may not just be for diabetes or weight, but perhaps for heart conditions like heart failure or coronary artery disease, which may be useful for these drugs," he said.

"It will be interesting to see whether this effect is independent of weight loss. So if they could somehow structure a study that compares patients on these types of drugs and their diuretic requirement with patients on other drugs and similar weight loss (and) compare their diuretic use to see if there is a benefit independent of weight loss."

Dr. Mir Ali, Bariatric Surgeon

Tadwalkar noted that he would like to see additional studies focusing on even more meaningful endpoints.

"The key endpoints of heart failure are hospitalization rates or readmission rates, and of course mortality - are people living longer because of this?" he continued.

"Anything we can do to move this needle forward for patients with HFpEF is important - we need to look at these endpoints in another trial or other studies."