Can semaglutide or tirzepatide lower your risk of heart failure hospitalization and death?

If you have obesity, type 2 diabetes, and have been told you have heart failure with preserved ejection fraction (HFpEF), you are not alone. HFpEF is now the most common form of heart failure. Until recently, there were few treatments that made a measurable difference. That may be changing.

A large real-world study just published in JAMA (Krüger et al., 2025) shows that two medications you may already recognize, semaglutide (Ozempic or Wegovy) and tirzepatide (Mounjaro or Zepbound), can reduce your risk of hospitalization for heart failure or death from any cause by over 40 percent. These results strengthen earlier trial findings and confirm their benefit in routine clinical practice.

What Was Studied?

Researchers analyzed health data from over 90,000 patients with type 2 diabetes and HFpEF. They compared people who started semaglutide or tirzepatide to those who started sitagliptin, a blood sugar medication that does not affect heart failure risk. This made sitagliptin a useful control group.

• People taking semaglutide had a 42 percent lower risk of hospitalization or death compared to those taking sitagliptin (hazard ratio 0.58)
• Those taking tirzepatide had an even greater 58 percent lower risk (hazard ratio 0.42)
• When comparing tirzepatide directly to semaglutide, there was no meaningful difference in outcomes

This supports the use of either medication for patients living with this type of heart failure.

Why This Matters

HFpEF is a form of heart failure in which the heart pumps normally but cannot relax properly. This leads to symptoms like fatigue, shortness of breath, and swelling in the legs. It is especially common in people with obesity, insulin resistance, and type 2 diabetes.

For years, there were few therapies that helped. These new results suggest that semaglutide and tirzepatide not only improve weight and blood sugar, but also reduce the risk of serious heart-related outcomes. Some of these benefits appear early, before much weight loss occurs. That suggests these drugs may act directly on the cardiovascular system, reducing inflammation, improving blood vessel function, or shifting kidney fluid balance.

Which Drug Is Better?

Tirzepatide had a slightly lower event rate than semaglutide, but the difference was small and not statistically significant. Both drugs appear highly effective for patients with HFpEF and type 2 diabetes. The choice between them may come down to factors like cost, insurance coverage, tolerability, and availability.

What About Side Effects?

No increased risk of serious side effects was seen with either drug. Researchers tracked gastrointestinal issues, infections, and other complications, and the results were reassuring. These medications appear safe to use even in patients with multiple chronic conditions.

What Should You Do?

If you have type 2 diabetes and obesity, and especially if you have heart failure or symptoms such as shortness of breath, fluid retention, or limited exercise tolerance, talk to your doctor. Semaglutide and tirzepatide are more than just weight loss drugs. They may protect your heart and extend your life.

These findings signal a shift in how we think about treating HFpEF. For patients with metabolic dysfunction, addressing the root cause may do more than improve symptoms; it may change the trajectory of the disease.