How the weight loss drug tirzepatide is also helping heart failure patients

CHICAGO — ­New clinical trial results on the diabetes and obesity drug tirzepatide have doctors buzzing about its potential to treat heart failure, keep weight off and prevent type 2 diabetes.

One of the newer heavy hitters in the ever-growing lineup of this class of drugs, tirzepatide is sold under the brand names Mounjaro (for type 2 diabetes) and Zepbound (for weight loss). It is a cousin of semaglutide, the main ingredient in the wildly popular medications Ozempic and Wegovy (SN: 5/22/24).

In one new tirzepatide study, the vast majority of participants remained diabetes free after three years using the drug. On average, those on the highest dose lost nearly 20 percent of their body weight, researchers reported November 13 in the New England Journal of Medicine. And in a different study of people with heart failure, tirzepatide offered some protection from further heart problems, researchers reported November 16 at the annual American Heart Association meeting and in the New England Journal of Medicine.

Together, the results add to the evidence supporting tirzepatide’s effects and safety, says Susan Yanovski, a physician and nutrition specialist at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. That’s “critically important when you have conditions where millions and millions of people are going to be taking these drugs long-term,” she says.

Both tirzepatide and semaglutide mimic GLP-1, a hormone that helps regulate blood sugar levels and appetite (SN: 12/13/23). But while semaglutide mimics just GLP-1, tirzepatide also mimics an additional hormone, GIP. That dual action may give the drug a bit more juice. In clinical trials, people tend to lose more weight on tirzepatide than on semaglutide.

But until now, scientists didn’t have much long-term data on tirzepatide’s effects. That’s where results from one of the new studies come in. In a clinical trial called SURMOUNT-1, scientists tracked overweight or obese adults with prediabetes given either tirzepatide or a placebo for over three years. Depending on the drug dose, participants lost between 12 and 20 percent of their body weight, on average. And only about one percent, 10 out of 762 people, developed diabetes. That’s compared with 13 percent, 36 out of 270 people, who developed diabetes while taking the placebo.

“Those are very valuable results,” says Daniel Drucker, an endocrinologist at the University of Toronto. Scientists knew that tirzepatide could cause substantial weight loss, but “delaying the onset of diabetes is also a benefit,” he says.

Tirzepatide may also benefit the heart

New results from the other study, a clinical trial called SUMMIT, suggest tirzepatide can help some people with heart failure. The trial included people whose hearts squeeze normally but have trouble filling with blood. It’s called heart failure with preserved ejection fraction, and obesity increases people’s risk. The heart condition affects up to 32 million people worldwide and the number is rising.

“It’s a looming public health crisis,” says Nancy Sweitzer, a heart failure cardiologist at Washington University School of Medicine in St. Louis. In people with this type of heart failure, blood can back up in the blood vessels, building pressure and forcing fluid to leak into tissues. “It’s like the sump pump in your basement,” Sweitzer says. “If it’s not pumping effectively, the water rises.”

Fluid leaking into the lungs makes it hard for people to breathe; really ill patients will describe a feeling of drowning, she says. They can also experience fatigue and swelling in the legs, among other symptoms.

Effective medications are limited. Until just a few years ago, doctors really didn’t have anything that worked, says Clyde Yancy, chief of cardiology at the Northwestern University Feinberg School of Medicine in Chicago.

In the trial, researchers enrolled more than 700 obese people with the heart failure condition. Those on the drug were less likely to die of cardiovascular causes or have their heart failure condition worsen compared with people taking the placebo. Those problems occurred in 36 of 364 patients taking tirzepatide, or 10 percent, versus 56 of 367 patients, or 15 percent, in the placebo group.

The drug did not reduce overall mortality, but it did affect patients’ quality of life. Compared with people taking the placebo, those on tirzepatide were able to walk farther and reported higher scores on a questionnaire that gauged how they were feeling.

Those are all important outcomes, Yancy says. In his practice, he hardly ever hears middle-aged and older patients say they want to live longer. Instead, they tell him, “I want to feel better. I want to be able to play with my grandchildren. I want to be able to go for a walk with my spouse.”

How GLP-1 drugs may improve heart health

The trial results add to a growing pile of evidence that GLP-1s help the heart. And shedding pounds may not be the only thing driving cardiovascular gains.

In a large clinical trial reported in 2023, researchers showed that semaglutide cut the risk of major cardiovascular problems, like heart attack and stroke (SN: 11/15/23). Those benefits started showing up before participants had lost a lot of weight — a clue that semaglutide may somehow directly protect the heart. “There are a lot of hints that these benefits are independent of weight loss,” Drucker says.

Other results from the SUMMIT tirzepatide trial have starting to capture a picture of what’s happening. MRI images taken before participants started taking the drug show that their hearts are heavy, and also swaddled in fat, Christopher Kramer, chief of cardiology at the University of Virginia in Charlottesville reported at the meeting and in the Journal of the American College of Cardiology. After a year on the drug, heart weight dropped and so did the amount of surrounding fat, Kramer says. “It’s melting away.”

Tirzepatide also reduced blood pressure and signs of inflammation. Those factors could help explain the benefits seen in heart failure patients, cardiologist Barry Borlaug reported at the meeting and in Nature Medicine. But as for whether the drug’s effects occur via weight loss or something different, “we really can’t tease it out,” said Borlaug, of the Mayo Clinic in Rochester, Minn.

Scientists may glean more hints in future tirzepatide trials. Drucker is looking forward to the results of one tracking outcomes such as heart attack and stroke in thousands of people with type 2 diabetes. That trial, called SURPASS-CVOT, will finish in mid-2025 and could “really give us the details we need to see how effective tirzepatide is in reducing heart disease,” he says.

Even if tirzepatide follows in semaglutide’s heart health–boosting footsteps, both drugs come with some big caveats. Patients can experience diarrhea, nausea, constipation and vomiting.

And as many as half or more of people on the medications stop taking them within a year. People may quit the drugs because they can’t tolerate them, can’t access them or simply can’t afford them, Yanovski says.

Scientists already know that going off the drug can reverse its weight loss effects. The same is probably true for any heart benefits, said Milton Packer, a cardiologist at Baylor University Medical Center in Dallas who reported the heart failure study results at the meeting.

And it’s not always clear who exactly might benefit from treatment. Clinical trials focus on specific populations of people to determine safety and efficacy, but many individuals outside of these groups are eligible for the drugs, scientists reported November 25 in JAMA Internal Medicine.

Yanovski stresses the importance of doctors working closely with patients after prescribing the medications. Physicians should be watching for how well patients are tolerating the drugs and when is safe to move up to a higher dose. But many people are getting these drugs online, making that kind of care difficult, she says. You want a clinician who knows your medical history and can talk about risks and benefits, Yanovski says — someone who can “really follow your health.”