A recent study published in the New England Journal of Medicine shows that the weight loss drug tirzepatide (AKA Mounjara and Zepbound) gave patients recovering from heart failure a significant survival boost.
Patients suffering from diastolic heart failure and obesity who were given Tirzepatide were less likely to die within a year, reported fewer heart failure symptoms, and an improved quality of life compared to those given a placebo.
What makes a heart fail?
The most common cause of heart failure in adults occurs when the left side of the heart has difficulty pumping fresh oxygenated blood around the body. Diastolic, or preserved ejection fraction heart failure (HFpEF) happens when the muscle in the left side of the heart is not capable of filling properly due to increased stiffness.
This leads to symptoms that include fatigue, less capacity for exercise, and swelling of hands and feet. Doctors have found that obesity, high blood pressure, diabetes, age and kidney disease seem to contribute to a person’s risk of developing diastolic heart failure. While turning back time is impossible, changing up your diet, activity levels and quitting smoking can help with most of the other causes.
Limited options for diastolic heart failure
For people with obesity, who may also have mobility issues, getting more active can be a challenge. Could weight loss drugs, or medications that control blood sugar be the answer? Researchers speculated that giving a helping hand to heart failure patients struggling to manage their metabolism could improve their chances of getting back on their feet.
Jeff Emmick, MD, PhD, senior vice president on product development at Eli Lilly explained in a press release “despite a continuing increase in the number of people with both HFpEF and obesity, treatment options remain limited” he says “In a first-of-its-kind trial, tirzepatide reduced severity of symptoms and improved heart failure outcomes in people with HFpEF and obesity”.
Does tirzepatide help heart failure?
Researchers across 146 hospitals across the world participated in a double-blind, randomized, placebo-controlled trial to test whether using the weight loss drug would improve outcomes for people with a BMI of 30 kg/m2 or more with HFpEF.
The study followed over 700 subjects across various countries for a year, after which doctors reported clinical outcomes. The results showed that Tirzepatide reduced the risk of negative heart failure outcomes by 38%.
Better hearts in a year with tirzepatide
Seven hundred and thirty one patients were randomly assigned to one of two groups. Neither patients nor doctors knew who was in each group. One group received weekly injections with tirzepatide, the other were given a placebo. The researchers followed the patients for at least 52 weeks. After a year, subjects attended a follow up visit with their doctor who assessed their progress with a number of clinical tools.
A little over a year after their treatment started, patients who got the drug had lost an average of 15.7% of their body weight vs 2.2% of those given the placebo. They also demonstrated a 38% reduction in signs of ongoing heart failure.
How did they measure success?
Objective measures of heart failure included number of urgent hospital visits related to heart failure, prescriptions for oral diuretics to relieve swelling, and death.The drug group also reported improvements in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire.
Patients in the tirzepatide group experienced an improvement of 24.8 points from baseline compared to 15 points from the placebo. This questionnaire measures symptoms, physical and social limitations, and quality of life in patients with heart failure.
Tirzepatide patients were also more physically able than placebo cohorts. They showed improvements in 6-Minute Walk-Test Distance scores and reduction in high sensitivity C-reactive protein. This translates to an increase in patient exercise capacity and a decrease in overall inflammation.
What does tirzepatide do?
Tirzepatide works similarly to trendy GLP-1RA drugs, Ozempic and Wegovy. These drugs mimic natural hormones controlling blood sugar and appetite in the body. Chemists at Eli Lily claim that Tirazepatide has more potent effects than its rivals because it targets glucose-dependent insulinotropic polypeptide receptors (GIP) in addition to GLP-1.
Like GLP-1, GIP is involved in appetite and regulating blood sugar. Researchers are, however, discovering previously unknown functions of this hormone, as interest in its application for weight loss has increased.
How does tirzepatide help with heart failure?
While it’s clear that tirzepatide had a useful effect on symptoms of heart failure, the biological mechanism for this is not cut and dried. Most likely, losing weight along with reducing blood pressure and inflammation helped to reduce the amount of strain put on the heart. It’s also possible that metabolic processes directly modulated by GIP and GLP-1 are directly involved in the cellular changes to the heart muscle wall that make it stiff. Further research is needed to understand how tirzepatide works, but for now, knowing that it does work is good news for people with diastolic heart failure.
Weight loss for a healthier heart?
The FDA currently has approved tirzepatide to complement diet and exercise in adults with type 2 diabetes, obesity, or those overweight with weight-related comorbid conditions. The study concluded with minimal adverse affects showing mainly gastrointestinal side effects, which led to a discontinuation of only 6.3% in the Tirzepatide group.
References
- Eli Lilly and Company. (2024, December 4). Lilly’s tirzepatide superior to Wegovy (semaglutide) in head-to-head trial showing an average weight loss of 20.2% vs 13.7%. Retrieved from https://www.lilly.com/en-CA/news/press-releases/2024.12.4-tirzepatide-surmount-5-h2h.
- Maxwell, Y. (2024, August 1). SUMMIT Meets Primary Endpoint: Safety, Efficacy of Tirzepatide: Topline Results. TCTMD. Retrieved from https://www.tctmd.com/news/summit-meets-primary-endpoint-safety-efficacy-tirzepatide-topline-results.
- Dharam J, K. (2024, November 16). A Study of Tirzepatide in Participants With Heart Failure With HFpEF and Obesity – SUMMIT. American College of Cardiology. Retrieved from https://www.acc.org/latest-in-cardiology/clinical-trials/2024/11/15/15/13/summit.
- Packer, M., Zile, M. R., Kramer, C.M, Baum, S. J., Litwin, S. E., Menon, V., … Borlaug, B. A., (2024, November 16th, 2024). Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine. Retrieved from https://www.nejm.org/doi/abs/10.1056/NEJMoa2410027.
- Eli Lilly and Company. (2024, August 1st). Lilly’s tirzepatide successful in phase 3 showing benefit in adults with heart failure with preserved ejection fraction and obesity. Retrieved from https://investor.lilly.com/node/51151/pdf.
- Spertus, J. A., Jones, P. G., Sandhu, A. T., & Arnold, S. V. (2020). Interpreting the Kansas City Cardiomyopathy Questionnaire in clinical trials and clinical care: JACC State-of-the-Art Review. Journal of the American College of Cardiology.
- Yu X, Chen S, Funcke JB, et al. The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice. Cell Metab. 2025;37(1):187-204.e7. doi:10.1016/j.cmet.2024.11.003
A recent study published in the New England Journal of Medicine shows that the weight loss drug tirzepatide (AKA Mounjara and Zepbound) gave patients recovering from heart failure a significant survival boost. Patients suffering from diastolic heart failure and obesity who were given Tirzepatide were less likely to die within a year, reported fewer heart failure symptoms, and an improved quality of life compared to those given a placebo. The most common cause of heart failure in adults occurs when the left side of the heart has difficulty pumping fresh oxygenated blood around the body. Diastolic, or preserved ejection fraction heart failure (HFpEF) happens when the muscle in the left side of the heart is not capable of filling properly due to increased stiffness. This leads to symptoms that include fatigue, less capacity for exercise, and swelling of hands and feet. Doctors have found that obesity, high blood pressure, diabetes, age and kidney disease seem to contribute to a person’s risk of developing diastolic heart failure. While turning back time is impossible, changing up your diet, activity levels and quitting smoking can help with most of the other causes. For people with obesity, who may also have mobility issues, getting more active can be a challenge. Could weight loss drugs, or medications that control blood sugar be the answer? Researchers speculated that giving a helping hand to heart failure patients struggling to manage their metabolism could improve their chances of getting back on their feet. Jeff Emmick, MD, PhD, senior vice president on product development at Eli Lilly explained in a press release “despite a continuing increase in the number of people with both HFpEF and obesity, treatment options remain limited” he says “In a first-of-its-kind trial, tirzepatide reduced severity of symptoms and improved heart failure outcomes in people with HFpEF and obesity”. Researchers across 146 hospitals across the world participated in a double-blind, randomized, placebo-controlled trial to test whether using the weight loss drug would improve outcomes for people with a BMI of 30 kg/m2 or more with HFpEF. The study followed over 700 subjects across various countries for a year, after which doctors reported clinical outcomes. The results showed that Tirzepatide reduced the risk of negative heart failure outcomes by 38%. Seven hundred and thirty one patients were randomly assigned to one of two groups. Neither patients nor doctors knew who was in each group. One group received weekly injections with tirzepatide, the other were given a placebo. The researchers followed the patients for at least 52 weeks. After a year, subjects attended a follow up visit with their doctor who assessed their progress with a number of clinical tools. A little over a year after their treatment started, patients who got the drug had lost an average of 15.7% of their body weight vs 2.2% of those given the placebo. They also demonstrated a 38% reduction in signs of ongoing heart failure. Objective measures of heart failure included number of urgent hospital visits related to heart failure, prescriptions for oral diuretics to relieve swelling, and death.The drug group also reported improvements in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire. Patients in the tirzepatide group experienced an improvement of 24.8 points from baseline compared to 15 points from the placebo. This questionnaire measures symptoms, physical and social limitations, and quality of life in patients with heart failure. Tirzepatide patients were also more physically able than placebo cohorts. They showed improvements in 6-Minute Walk-Test Distance scores and reduction in high sensitivity C-reactive protein. This translates to an increase in patient exercise capacity and a decrease in overall inflammation. Tirzepatide works similarly to trendy GLP-1RA drugs, Ozempic and Wegovy. These drugs mimic natural hormones controlling blood sugar and appetite in the body. Chemists at Eli Lily claim that Tirazepatide has more potent effects than its rivals because it targets glucose-dependent insulinotropic polypeptide receptors (GIP) in addition to GLP-1. Like GLP-1, GIP is involved in appetite and regulating blood sugar. Researchers are, however, discovering previously unknown functions of this hormone, as interest in its application for weight loss has increased. While it’s clear that tirzepatide had a useful effect on symptoms of heart failure, the biological mechanism for this is not cut and dried. Most likely, losing weight along with reducing blood pressure and inflammation helped to reduce the amount of strain put on the heart. It’s also possible that metabolic processes directly modulated by GIP and GLP-1 are directly involved in the cellular changes to the heart muscle wall that make it stiff. Further research is needed to understand how tirzepatide works, but for now, knowing that it does work is good news for people with diastolic heart failure. The FDA currently has approved tirzepatide to complement diet and exercise in adults with type 2 diabetes, obesity, or those overweight with weight-related comorbid conditions. The study concluded with minimal adverse affects showing mainly gastrointestinal side effects, which led to a discontinuation of only 6.3% in the Tirzepatide group.
What makes a heart fail?
Limited options for diastolic heart failure
Does tirzepatide help heart failure?
Better hearts in a year with tirzepatide
How did they measure success?
What does tirzepatide do?
How does tirzepatide help with heart failure?
Weight loss for a healthier heart?
References
