Weight loss medications linked to major reductions in heart failure hospitalisations and death

Key Takeaways:

• People with heart failure with preserved ejection fraction (HFpEF), obesity, and Type 2 diabetes who were prescribed semaglutide or tirzepatide had over 40 per cent lower risk of hospitalisation or death compared with those taking sitagliptin.
• Researchers analysed real-world data from more than 90,000 patients, making this the largest study to date on GLP-1 medications in HFpEF.
• Findings suggest semaglutide and tirzepatide could become a new treatment option for heart failure, though they are not yet approved for this use.
  

A new avenue for treating a difficult condition

A major new study has found that weight loss drugs semaglutide and tirzepatide may significantly reduce the risk of hospitalisation and death among people living with heart failure with preserved ejection fraction (HFpEF), obesity, and Type 2 diabetes.

The research, conducted by investigators at Harvard-affiliated Mass General Brigham (MGB), showed that initiating either of the two medications was linked to an over 40 per cent reduction in the combined risk of being hospitalised with heart failure or dying from any cause, compared with patients who received a placebo by proxy.

HFpEF is a common form of heart failure in which the heart muscle becomes thick and stiff. Although the pumping function remains intact, the heart cannot fill adequately with blood, leaving the body’s organs and tissues under-supplied. HFpEF disproportionately affects people with obesity and Type 2 diabetes, and current treatment options remain limited.

“Despite the widespread morbidity and mortality burden of HFpEF, current treatment options are limited,” said corresponding author Nils Krüger of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital and a postdoctoral research fellow at Harvard Medical School. “Both semaglutide and tirzepatide are well-known for their effects on weight loss and blood sugar control, but our study suggests they may also offer substantial benefits to patients with obesity and Type 2 diabetes by reducing adverse heart failure outcomes.”

Largest analysis of GLP-1 medications in HFpEF

To strengthen the evidence base beyond small, randomised clinical trials, the research team examined real-world data from more than 90,000 people with HFpEF, obesity, and Type 2 diabetes. Findings, published in JAMA and presented at the European Society of Cardiology Congress, demonstrated a significant reduction in both heart failure hospitalisation and all-cause mortality among patients who began treatment with semaglutide or tirzepatide.

While previous trials of GLP-1 receptor agonists in obesity-related HFpEF showed promising results, they involved relatively small study populations. Regulatory agencies and professional societies have therefore not yet approved or endorsed the use of these medications for HFpEF.

To address this gap, the MGB team used three large United States insurance claims databases to emulate two earlier placebo-controlled trials, but with study populations that were on average 19 times larger.

Methodology and comparative effectiveness

The researchers compared the one-year risk of hospitalisation for heart failure or death among new users of semaglutide or tirzepatide with that of patients prescribed sitagliptin, a diabetes medication known not to affect HFpEF. This “active placebo” comparator allowed them to verify earlier clinical trial results in much larger and more representative groups of patients.

Overall, semaglutide and tirzepatide were each associated with more than 40 per cent lower risk of hospitalisation or death compared with sitagliptin. Both drugs demonstrated similar effectiveness in this context.

Importantly, both medications also maintained acceptable safety profiles in this real-world study, reinforcing findings from earlier clinical trials.

Future directions for research

Although the findings are compelling, GLP-1 receptor agonists are not currently licensed for the treatment of heart failure. The research team emphasised the need for further investigation to determine the long-term impact of these medications, to identify which subgroups of people with HFpEF may benefit the most, and to explore whether they also reduce additional cardiovascular risks beyond heart failure.

“By using nationwide data and an innovative methodological approach, our team was able to expand the findings of previous trials to larger populations more representative of HFpEF patients treated in clinical practice,” Krüger explained. “Our findings show that in the future, GLP-1 targeting medications could provide a much-needed treatment option for patients with heart failure.”

CCH Insight:

These are very positive results, and add to the evidence base for the benefits of GLP-1 medications for patients with HFpEF. It is an observational study, so large-scale clinical trials are needed to confirm these findings, but it probably won’t be long before GLP-1 medications are licensed for treatment of HFpEF, yet another condition to add to the growing list that can be treated with these drugs.