Tirzepatide improves heart health and function in obese HFpEF patients

In the international SUMMIT trial, adults with heart failure preserved ejection fraction (HFpEF) and obesity taking tirzepatide for up to 3 years had a reduced combined risk of worsening heart failure events and cardiovascular death, and improved health status and physical function in comparison to participants taking placebo, according to late-breaking science presented today at the American Heart Association’s Scientific Sessions 2024. The meeting, Nov. 16-18, 2024, in Chicago, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

Tirzepatide is a long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, approved by the U.S. Food and Drug Administration for treatment of Type 2 diabetes for weight management in people with overweight or obesity. Previous research has confirmed a 12%-21% weight loss in patients with obesity taking tirzepatide.

Obesity contributes to worsening heart failure, and while tirzepatide causes considerable weight loss, research is lacking on its effects on cardiovascular outcomes. This is the first trial that tested the effect of any medication on major heart failure outcomes in patients with HFpEF and obesity.”


Milton Packer, M.D., lead study author, distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas and visiting professor at Imperial College in London

The international SUMMIT trial enrolled a total of 731 adults, ages 40 years and older, who had been diagnosed with HFpEF and obesity at health centers in nine countries including the U.S. All trial participants had measurements of ejection fraction ≥50%, and they all had body mass index (BMI) measurements of ≥30 kg/m2, the criteria for a diagnosis of obesity.

In this double-blind trial, participants were randomly assigned in nearly equal numbers to either tirzepatide or placebo. (A double-blind trial means that neither the patients nor the health care team knew which treatment group patients were assigned.) Participants received a weekly injection of tirzepatide or placebo, and the weekly dose was gradually increased from 2.5 mg to a possible maximum dose of 15 mg per week. All participants continued taking their regular medications including those for heart failure while enrolled in the study.

With a median follow-up of two years, maximum of three years, researchers assessed the rates of health status and functional capacity, worsening heart failure events or death due to cardiovascular causes. Specifically, they tracked time-to-first occurrence for cardiovascular death or a worsening heart failure event requiring hospitalization, an urgent heart failure visit requiring intravenous drug therapy, or intensification of oral diuretics.

In addition, changes in participants’ health status and symptom burden were evaluated using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The KCCQ-CSS is a commonly used patient questionnaire of 23 questions to gauge a patient’s symptoms, physical function, quality of life and social function with heart failure during the previous two weeks.

The distance participants could walk within a six-minute timeframe, the 6-minute walk test; the KCCQ-CSS score; and high-sensitive C-reactive protein level in the blood were measured at enrollment and after 24 weeks and 52 weeks.

The study found participants in the tirzepatide group had a reduced combined risk of cardiovascular death and worsening heart failure events compared to the participants in the placebo group.

Specifically, the results found:

  • Cardiovascular death or worsening heart failure events occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, representing a 38% reduction in risk among those taking tirzepatide.
  • Worsening heart failure events occurred in 29 patients (8.0%) in the tirzepatide group compared to 52 (14.2%) in the placebo group, representing a 46% reduction in risk for those taking tirzepatide.
  • There were 15 cardiovascular deaths total among both groups, and 11 were not preceded by worsening heart failure, and 2 in the tirzepatide group occurred after patients had not taken the medication for more than 15 months. Among all participants, there were 34 deaths for any reason.
  • At one year, KCCQ-CSS scores were improved by an average of 6.9 points more in the tirzepatide group compared to the placebo group, indicating participants perceived greater improvement in health and function with tirzepatide.
  • Participants had a mean change in body weight: 11.9% greater weight loss in the tirzepatide group compared to the placebo group, measured at one year.
  • Participants in the tirzepatide group improved their six-minute walking distance test at one year by an average of 18.3 meters farther compared to the placebo group.
  • Participants in the tirzepatide group had less systemic inflammation, as indicated by a high-sensitivity C-reactive protein (hs-CRP) measure. When compared with placebo, on average, the difference in the percent changes in the tirzepatide group was 32.9%, indicating lower levels of inflammation. An hs-CRP blood test is able to detect low levels of inflammation in the body and is focused on assessing risk of heart disease and stroke.

“These results indicate tirzepatide produced meaningful benefits for people living with heart failure with preserved ejection fraction and obesity,” said Packer. “The patients experienced a lower combined risk of worsening heart failure events and cardiovascular disease death, along with improved health status and exercise tolerance. This is the first trial to demonstrate that a medication can change the clinical trajectory of the disease in patients with HFpEF and obesity.”

Study background and details:

  • Between April 20, 2021 and June 30, 2023, 1,494 patients with heart failure and obesity at 129 health centers in nine countries were screened for the trial. The health centers were in the U.S., Argentina, Brazil, China, India, Israel, Mexico, Russia and Taiwan.
  • 731 adults were enrolled; ages 40 years and older; mean age of 65.2 years; 53.8% were women; and a mean BMI of 38.3 kg/m2.
  • All participants had measurements of ejection fraction ≥50%, and they were randomly assigned to either tirzepatide or placebo: 364 in the tirzepatide group and 367 in the placebo group.
  • The median duration of follow-up was 104 weeks, and 15 patients (2%) were lost to follow-up by the conclusion of the study (4 in the tirzepatide group, 11 in the placebo group).
  • Every 1-6 months during the trial, body weight, heart failure symptoms, major worsening heart failure events, changes in heart failure medications and adverse events were monitored.
  • Approximately 4% of patients in the tirzepatide group discontinued treatment due to gastrointestinal symptoms.

An important limitation of the trial was that BMI was the body size measure used. People with HFpEF often have a higher than normal waist-to-height ratio, indicating visceral adiposity or high belly fat, with BMI lower than 30 kg/m2, which does not meet the criteria for a diagnosis of obesity. More research is needed to further clarify the most accurate parameters for patients who can benefit from treatment.

According to the American Heart Association’s 2024 Heart Disease and Stroke Statistics, heart failure affects an estimated 56 million people worldwide and greatly impacts a person’s ability to do everyday activities. Ejection fraction is a metric often used to diagnose and track the severity of heart failure, and it specifically measures how much blood the left ventricle pumps out with each contraction of the heart. A normal ejection fraction measurement is between 55% and 70%.

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