GLP-1s, Menopause and HFpEF: What STEP-HFpEF and SUMMIT Found

HFpEF (heart failure with preserved ejection fraction) is a type of heart failure where the heart still squeezes well but has become stiff and cannot relax and fill properly. Fluid backs up, which causes breathlessness, tiredness and swollen ankles. It is not a weak-heart problem. It is a stiff-heart problem.

HFpEF is more common in women than in men, and it tends to show up later in life. Obesity is one of its strongest drivers. Extra fat, especially visceral fat (the deep belly fat packed around your organs), releases inflammatory signals that can stiffen heart muscle over time. The menopause transition adds to this. The SWAN study (Study of Women's Health Across the Nation) found that women gain fat and see less favorable blood vessel and cholesterol changes around the final menstrual period. If you want the bigger picture on that, read our guide on [what SWAN found about menopause and heart disease risk](/blog/menopause-heart-disease-risk-what-swan-found).

This is why HFpEF sits right at the crossroads of weight, hormones and heart health. It is also why researchers chose it as a place to test GLP-1 medicines. If belly fat and inflammation help drive the stiffness, then losing weight with a drug like semaglutide or tirzepatide might ease it.

The symptoms are easy to blame on aging or menopause. Getting winded on stairs, needing more pillows to sleep, and swollen feet can all be written off. If you notice them, mention them to your doctor, because HFpEF is often missed in women.

STEP-HFpEF showed that semaglutide 2.4 mg weekly improved symptoms, exercise ability and weight in people with obesity and HFpEF. The trial enrolled 529 adults with a BMI of 30 or higher and HFpEF, and about 56% were women. They received semaglutide or placebo for 52 weeks (Kosiborod et al., NEJM 2023).

The two main results were measured together. The first was the KCCQ-CSS (Kansas City Cardiomyopathy Questionnaire clinical summary score), a 0 to 100 scale where higher means fewer symptoms and better function. It rose by 16.6 points with semaglutide versus 8.7 points with placebo. The second was body weight, which fell by 13.3% with semaglutide versus 2.6% with placebo.

People on semaglutide also walked farther in six minutes, by 21.5 meters compared with 1.2 meters on placebo. Levels of CRP, a blood marker of inflammation, also dropped more with semaglutide. A follow-up trial, STEP-HFpEF DM (NEJM 2024), tested 616 people who also had type 2 diabetes. Symptom scores improved by 13.7 points versus 6.4, and weight fell by 9.8% versus 3.4%.

These trials were not built to prove fewer hospital stays. Later pooled analyses of both trials suggested fewer heart failure events with semaglutide, but those were exploratory, so treat them as a hint and not as proof.

SUMMIT found that tirzepatide cut the combined risk of cardiovascular death or a worsening heart failure event by about 38% in people with obesity and HFpEF. The trial enrolled 731 adults and followed them for a median of about two years (Packer et al., NEJM 2025).

The primary outcome had two parts. One was the time to cardiovascular death or a worsening heart failure event, such as a hospital stay or an urgent visit needing IV diuretics. That event happened in 9.9% of people on tirzepatide and 15.3% on placebo, a hazard ratio of 0.62. A hazard ratio below 1 means a lower risk, so 0.62 equals a 38% relative reduction. Nearly all the difference came from fewer worsening heart failure events, since cardiovascular deaths were few in both groups.

The second part was the KCCQ-CSS score. It improved by about 6.9 points more with tirzepatide than with placebo. People on tirzepatide also lost about 11% of body weight more than the placebo group, and systolic blood pressure dropped as well.

SUMMIT is the first big trial to show a clear drop in hard heart failure events with a weight loss drug in HFpEF. If you are curious how tirzepatide stacks up against semaglutide more broadly, our [head-to-head review of SURMOUNT-5](/blog/tirzepatide-vs-semaglutide-surmount-5-head-to-head) goes into the details.

GLP-1 medicines probably help HFpEF through several routes at once, and weight loss is only part of the story. Losing visceral fat lowers inflammation and eases the load on the heart. Lower blood pressure reduces the pressure the heart has to pump against. Less fluid and salt retention may reduce the congestion that causes breathlessness.

Researchers also point to epicardial fat, the layer of fat that sits right on the surface of the heart. It can press on the heart and release inflammatory signals. Weight loss drugs seem to shrink it. In menopause, fat tends to move toward the belly and around organs, and our article on [GLP-1s and visceral fat in menopause](/blog/glp1-and-visceral-fat-in-menopause-targeting-belly-fat) explains why that shift matters.

There is a fair question about whether direct effects on the heart play a role too. GLP-1 receptors exist in heart tissue, but the evidence for strong direct effects is mixed. Most experts think the benefit comes mainly from weight, blood pressure, inflammation and fluid changes working together. Some of the improvement showed up before large amounts of weight were lost, which hints that more than weight is going on.

Whatever the exact mix, the result is the same in the trials. People felt better, walked farther and had fewer worsening events.

If you are in perimenopause or postmenopause and have obesity, these trials suggest that treating weight may also protect your heart, and that is worth discussing with your doctor. They do not mean GLP-1s are proven to prevent heart failure in people who do not have it. Both trials enrolled people who already had HFpEF and a BMI of 30 or higher.

They also do not mean everyone with menopause symptoms needs a GLP-1. Breathlessness in midlife has many causes, from anemia to thyroid problems to anxiety to lung disease. HFpEF is only one possibility. A doctor can check with a physical exam, blood tests including NT-proBNP (a hormone released when the heart is strained), and an echocardiogram (a heart ultrasound).

The heart benefit also fits a pattern we have seen elsewhere. The [SELECT trial](/blog/glp1-heart-health-what-the-select-trial-found) showed fewer heart attacks and strokes with semaglutide in people with heart disease and overweight. Our review of [GLP-1 heart protection in menopause](/blog/glp1-menopause-heart-protection-cardiovascular-benefits) pulls those threads together for midlife women.

One honest caution: women have been under-represented in many heart trials. STEP-HFpEF had a good share of women at about 56%, which is encouraging, but the studies were not designed to compare women who had gone through menopause with those who had not.

If you take heart or blood pressure medicines, tell your prescriber before starting a GLP-1, because doses sometimes need to come down as you lose weight and fluid. Diuretics (water pills) are the best example. If you eat and drink less, which is common on a GLP-1, you can become dehydrated, and that can strain your kidneys or drop your blood pressure too far. Our guide on [blood pressure on GLP-1 during menopause](/blog/blood-pressure-on-glp1-during-menopause-why-readings-drop) covers the signs to watch.

Watch for dizziness when you stand, a very low home reading, or much less urine than usual. Vomiting or diarrhea can make this worse, so call your care team if they last more than a day.

People with heart failure are also told to track daily weight. A gain of more than about 2 to 3 pounds in a day, or 5 pounds in a week, can signal fluid build-up and needs a call to your doctor. On a GLP-1, your weight should trend down. A sudden rise is a red flag and not a plateau.

GLP-1s can also raise resting heart rate by a few beats per minute. That is usually minor, but it is worth knowing about if you have a heart rhythm problem. Our article on [resting heart rate on GLP-1](/blog/resting-heart-rate-on-glp1-why-it-rises-and-when-to-worry) explains when it matters.

This article is educational and not medical advice. Your cardiologist and prescriber should set your plan.

The medicine is one tool, and daily habits still carry a lot of weight. Aim for strength training twice a week to protect muscle, since the heart is a muscle too and lean mass supports fitness. Walk most days, building gradually. Prioritize protein, which most GLP-1 guides put around 1.2 to 1.6 grams per kilogram of body weight unless your kidney doctor says otherwise.

Keep sodium moderate if you have HFpEF, because extra salt holds water. Limit alcohol, which can raise blood pressure and trigger heart rhythm problems. Sleep matters too. Sleep apnea is common in midlife women and strains the heart, and the [SURMOUNT-OSA findings in menopause](/blog/glp1-sleep-apnea-menopause-surmount-osa-what-it-means) show how weight loss can help.

Keep your regular checkups. Ask for blood pressure, cholesterol, A1C and kidney function tests, and ask your doctor when to repeat them while your weight is changing. Bring a list of every medicine and supplement you take, since some supplements can interact with heart drugs.

A short note of warmth: big health changes in midlife can feel like a lot at once. You do not have to fix everything this month. Small steady steps add up, and a good care team makes them easier.