GLP-1 receptor agonist (GLP-1 RA) drugs have been shown to reduce the number of deaths, amputations and hospitalizations in people with type 2 diabetes who have narrowed leg arteries associated with PAD (peripheral artery disease), according to a new independent study published today. American Heart Association Journalan open-access peer-reviewed journal of the American Heart Association.
Because peripheral artery disease, also known as PAD, has limited treatment options, clinicians should consider prescribing GLP-1, as GLP-1 RA shows significant benefit in high-risk patients, especially those with severe circulatory disorders in the legs. Our findings indicate that these drugs, in addition to managing blood sugar levels and weight loss, may improve the long-term health of PAD patients. ”
Aravinda Nanjundappa, MD, study author, interventional cardiologist in the Division of Invasive and Interventional Cardiology, Robert and Suzanne Tomisic Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland.
In this study, researchers examined the health records of more than 2,000 adults with type 2 diabetes and PAD to investigate the potential benefits of GLP-1 RA treatments. Researchers found that the positive effects of GLP-1 RAs on overall health exceeded those of metformin, the most widely prescribed drug for people with type 2 diabetes in most categories.
Among people taking GLP-1 RAs, compared to those taking metformin, the analysis found that:
- 26% reduction in all causes of death.
- Hospital admissions decreased by 13%.
- Cuts are reduced by up to 48%. and
- The need for procedures to open clogged arteries is reduced by approximately 36%.
- However, the rates of heart attacks, strokes, and serious kidney events were similar between both groups.
The researchers noted that the association between GLP1-RA and medical benefit was strongest among patients with severe PAD, including limb-threatening chronic ischemia, and participants with a BMI of 30 or higher, which is considered obese.
“PAD, which includes obesity and chronic limb-threatening ischemia, is associated with increased inflammation, decreased vascular function, insulin resistance, oxidative stress, and accelerated arteriosclerosis,” said study co-author Akiva Rosenzweig, MD, a cardiology fellow at the Cleveland Clinic. “These results show that GLP1-RA reduces inflammation, improves vascular function, and helps manage blood sugar levels.”
Strengths of this study include analyzing a large population and investigating both mortality and limb-related problems. Participants in the comparison group had to have received at least five prescriptions for metformin and no prescriptions for GLP-1 RAs during the study period. According to Nanjundappa et al., this approach strengthened the results of their analysis.
“GLP1-RA drugs may help extend the lifespan of patients with PAD and type 2 diabetes. They may also help reduce the risk of amputation and the number and duration of hospitalization. However, further research is needed to confirm these findings and understand the underlying mechanisms, whether this is due to reduced inflammation. It is also important to know whether RA is beneficial for PAD patients who do not have type 2 diabetes,” said Joshua J. Joseph, MD, MPH. FAHA is a volunteer expert for the American Heart Association and chair of the diabetes committee of the association’s Lifestyle and Cardiometabolic Health Council. Joseph, who was not involved in the study, is an associate professor of internal medicine and endowed professor of internal medicine research at The Ohio State University Wexner Medical Center in Columbus, Ohio.
According to the American Heart Association’s 2026 Heart Disease and Stroke Statistics, data from 2021 to 2023 shows that an estimated 29.5 million (10.6%) U.S. adults were diagnosed with type 2 diabetes. Approximately 12.5 million people over the age of 40 in the United States have PAD.
What are the details, background, design, and limitations of the study?
- The TriNetX database, a global federated real-world medical data network that connects researchers, clinicians, and industry partners from over 70 to 80 healthcare institutions, is a global, federated, real-world medical data network that connects researchers, clinicians, and industry partners from over 70 to 80 healthcare institutions. It was used to identify patients who had not had a new diagnosis of heart attack, end-stage renal disease, or stroke within a month.
- The researchers compared adults who were prescribed GLP1-RAs at least five times during the study period with a comparison group who had no record of GLP1-RA prescriptions throughout the study period. The comparison group had to have been prescribed metformin at least five times.
- The entire PAD group included 3,224 GLP-1 RA users and 6,087 non-GLP-1 RA users. The clogged leg artery subgroup included 750 GLP-1 RA users and 1,616 non-GLP-1 RA users. Additionally, the limb-threatening chronic ischemia subgroup included 3,395 GLP-1 RA users and 6,626 non-GLP-1 RA users. After matching, 2,133 patients per group were analyzed across PAD groups.
- Sixty-three percent of participants identified as white adults, 23% as black adults, and 45% as women.
- This study was limited in that it could not prove cause and effect. Additionally, electronic medical records (digital versions of patients’ medical records) may contain diagnostic coding errors that may impact the results of the analysis.
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american heart association
Reference magazines:
DOI: 10.1161/JAHA.125.045664
