Tirzepatide may improve outcomes in adults with congestive heart failure (by Patricia Toro, MD MPH)

November 26, 2024

Summary: The GLP-1 tirzepatide is associated with decreased death or worsening heart failure in those with existing heart failure and no diabetes. 

Likelihood of death or worsening heart failure

Weeks since randomization  
Source: Packer, et al New England Journal, November 16, 2024

Obesity can cause inflammation throughout the body, including the heart. That inflammation, along with the potential consequences of chronic obesity, can contribute to congestive heart failure (CHF), where the heart cannot adequately pump blood to meet the body’s needs.

A recent study in the New England Journal of Medicine looked at the impact of tirzepatide (Mounjaro and Zepbound) treatment on those with obesity and a specific type of CHF. In this randomized, double-blinded study, 731 patients, with an average age of 65 years who were obese (BMI > 30) and with CHF, were either randomized to: a) weekly tirzepatide (Zepbound) or b) a placebo for an average of 2 years. The researchers looked at 3 outcomes: 1) death from cardiovascular events, 2) worsening CHF heart function, and 3) self-reported health status.

The results were impressive! The tirzepatide group had significantly fewerdeaths or CHF events compared to the placebo group (9.9% versus 15.3%). This represented a 38% decrease in risk of death or worsening heart failure. The tirzepatide group also had significantly better self-reported health status over the placebo group. What was particularly impressive was how quickly these benefits accrued for the study participants.

At the same time, the tirzepatide group had more adverse events leading to stopping the intervention, compared to the placebo group (6.3% versus 1.4% placebo). Most of those adverse events were gastrointestinal side effects, which are a well-known hazard of taking any of the GLP-1 medications. The tirzepatide group also had more deaths (8 vs. 5), although this did not reach statistical significance, so could have been due to randomness.

This is a well-constructed study, and these results add to the growing evidence of the benefits of these medications. Two additional notes of caution. First, this study was sponsored by Eli Lilly, the maker of tirzepatide. But the study design (randomized, double blind) should limit any biases in the population. Second, the study looked specifically at individuals with a BMI > 30. Not all individuals with CHF are clinically obese, so these results are not generalizable to every person with CHF.

Implications for employers:

• This well-designed study was for tirzepatide only, but the outcomes likely extend to the most effective GLP-1s more broadly.

• The age of this study population is older than most commercial populations, but the outcomes may be similar in younger patients with CHF and a BMI of 30 or higher.

• This study adds to the growing evidence of the clinical benefits of GLP-1s beyond diabetes or obesity alone. Lilly plans to submit data to the FDA for approval of tirzepatide to treat this type of heart failure.

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Tomorrow: Follow ups and shorts