Semaglutide may improve symptoms of heart failure 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 possibility of using this class of drugs for other conditions.

These include sleep apnea, high blood pressure, non-alcoholic 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, the scientific congress of the European Society of Cardiology (ESC), reports that semaglutidereduces 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 use of diuretics.

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 March 2024, involving 1,145 participants with a mean age of 70 years.

In both trials, participants had HFpEF, which is associated with obesity, and a KCCQ-CSS score of less than 90, which measures the quality of life of 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.

For those taking semaglutide and loop diuretics, diuretic dosage was reduced by 17% after 52 weeks.

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

"Seeing the data on diuretics that these people can potentially reduce their diuretic dose, they need to increase their diuretic dose less, and they just need less diuretics when they're treated with semaglutide—that's 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 dose loop diuretic category lost an average of 6.9% of their body weight.

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

"There was evidence of a significant reduction in mean loop diuretic dose, less likelihood of diuretic dose increase, and greater likelihood of diuretic dose reduction 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 category of patients."

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 cannot fill with blood normally. In HFpEF, the left ventricle of the heart cannot relax and fill with blood as it should.

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

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

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

Previous studies have shown that about 84% of cases HFpEF is caused by overweight or obesity, lifestyle changes such as reducing salt intake, increasing physical activity and weight loss, may also help with HFpEF.

Potential expansion of indications for semaglutide

After reviewing this 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 is not surprising that semaglutide-based medications that help people lose weight improve heart conditions such as 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 the use of these drugs, which may not only be for diabetes or weight, but perhaps for heart diseases such as heart failure or coronary artery disease, which may be beneficial for these drugs." " he said.

"It will be interesting to see if 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 need for diuretics with patients on other drugs and similar weight loss ( i) compare their use of diuretics 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 targeting even more meaningful endpoints.

"The main 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 should look at these endpoints in another trial or other studies."