As the use of glucagon-like peptide-1 (GLP-1) receptor agonist medications continues to rise, researchers are examining how these medications might affect other aspects of a person’s health outside of type 2 diabetes treatment and weight loss.
Past studies show that GLP-1 drugs may help lower the risk for or treat conditions like kidney disease, metabolic syndrome, liver disease, sleep apnea, alcohol use disorder, Alzheimer’s disease, and cardiovascular disease.
Now, a new study published in the journal The BMJ reports further evidence of a link between GLP-1 medications and heart health benefits.
The researchers found that adding the GLP-1 medication tirzepatide — the active ingredient in Mounjaro and Zepbound — to standard care for people with both type 2 diabetes and heart disease may help lower their risk for a major cardiovascular event, such as a stroke or heart attack.
For this study, researchers analyzed clinical practice data from almost 53,000 people with both type 2 diabetes and heart disease.
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Study participants were split into two groups — one group started taking tirzepatide and the second group took the diabetes medication sitagliptin — and scientists measured any reduction in major adverse cardiovascular events (MACE), which include heart attack, stroke, and death from any cause.
“GLP-1–based medications were initially developed to improve glucose control, but their effects appear to extend well beyond blood sugar and weight loss,” Nils Krüger, MD, MPH, a physician data scientist in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Department of Medicine at Brigham and Women’s Hospital in Boston, lead author of this study, told Medical News Today.
“Cardiovascular disease remains the leading source of illness and death globally, so it is important to understand whether these medications can also reduce heart attacks, strokes, heart failure, and mortality,” Krüger continued.
“Studying these broader effects helps clinicians and patients make treatment decisions based on the full range of potential benefits and risks rather than on metabolic outcomes alone,” he said.
At the study’s conclusion, researchers found that after one year, participants in the tirzepatide group had a 2.9% MACE risk, compared with 4.4% in the sitagliptin group.
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Scientists also estimated that for every 70 study participants who started tirzepatide, one case of MACE could be prevented.
“These findings translate the relative effect into a measure that is tangible for clinicians and patients,” Krüger said.
“The 1.4-percentage-point absolute difference means that, among patients similar to those in our study, treating approximately 70 people with tirzepatide rather than the cardiovascular-neutral comparator for one year would be associated with one fewer major cardiovascular event.”
— Nils Krüger, MD, MPH
Additionally, researchers discovered that tirzepatide use was linked to a 33% lower risk of having a heart attack, when compared to sitagliptin.
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“The reduction in myocardial infarction is important because heart attack is one of the most serious and clinically consequential complications of diabetes and established cardiovascular disease,” Krüger explained. “The finding also suggests that the overall reduction in major cardiovascular events was not driven solely by mortality.”
Krüger said the mechanisms behind tirzepatide possibly helping lower MACE risk are likely multifactorial.
“Tirzepatide improves glucose control, reduces body weight, and may favorably influence blood pressure, lipids, inflammation, and other cardiometabolic risk factors. In our study, the cardiovascular event curves began to separate relatively early, before substantial weight loss would generally be expected, raising the possibility that vascular or anti-inflammatory effects may also contribute.”
— Nils Krüger, MD, MPH
“The lower risks of serious infections and infection-related mortality suggest that non-atherosclerotic pathways may be involved as well, although the exact mechanisms require further investigation,” Krüger added.
Krüger said their next steps in this research are to examine whether these benefits persist over longer follow-up and can be replicated in other populations and healthcare systems.
“We also want to better understand the mechanisms underlying the reductions in infection-related events, and to determine how tirzepatide compares directly with other cardiometabolic therapies, including other incretin-based treatments and SGLT2 inhibitors,” he added.
MNT spoke with Cheng-Han Chen, MD, a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, who commented that this study adds to a rapidly expanding body of evidence highlighting the cardiometabolic benefits of GLP-1 receptor agonists.
“Beyond their established role in managing type 2 diabetes, these medications are increasingly associated with improved cardiovascular outcomes,” Chen, who was not involved in this study, explained. “GLP-1 receptor agonists have emerged as one of the most impactful therapeutic classes in recent years.”
“A growing number of studies demonstrate benefits across a spectrum of cardiometabolic conditions, suggesting these agents could play a meaningful role in lowering the overall burden of cardiovascular disease at a population level,” he added.
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MNT also spoke with Sanjeev Kumar Gulati, MD, FACC, executive deputy director of Baptist Health Heart & Vascular Care and system chief of cardiovascular medicine at Baptist Health South Florida, who likewise was not involved in this study.
Gulati said that while these findings are encouraging and consistent with the growing amount of evidence suggesting that tirzepatide provides benefits beyond just blood sugar management and weight loss, the most important question is how they affect overall health and long-term outcomes.
“As evidence continues to emerge regarding heart health, kidney protection, weight management, and other potential benefits, ongoing research will help us optimize care and ensure that the right patients receive the greatest benefit from these therapies,” he continued.
“I would like to see longer-term studies that help determine whether the cardiovascular benefits observed with tirzepatide are sustained over many years and whether they extend to broader patient populations, including those without established cardiovascular disease. Randomized studies will be important for us to have a better understanding of the potential benefits of tirzepatide.”
— Sanjeev Kumar Gulati, MD, FACC
