GLP-1 Drugs Cut Heart Risks in Overweight Diabetics, Safeguard Kidneys for All: JAMA
Taiwan: A recent study has found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes delivers body mass index (BMI)-dependent cardiovascular benefits and consistent kidney protection.
The findings, published in JAMA Network Open, suggest that while heart-related benefits are more pronounced in individuals with a higher BMI, kidney protection appears to extend across all BMI categories.
The study was conducted by Tien-Hsing Chen from the Division of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan, and colleagues. Using data from the Chang Gung Research Database spanning 2011 to 2022, the researchers compared outcomes in patients who initiated GLP-1 RAs with those who were prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors, a widely used alternative therapy considered neutral for cardiovascular and renal effects.
A total of 97,156 individuals with type 2 diabetes were initially identified, and after propensity score matching, 7200 patients were included in the analysis, comprising 1841 pairs with BMI below 25 and 5359 pairs with BMI of 25 or greater. The primary outcomes assessed were major adverse cardiovascular events (MACE), which included cardiovascular death, myocardial infarction, ischemic stroke, or hospitalization for heart failure, as well as composite kidney outcomes defined by significant declines in estimated glomerular filtration rate or progression to dialysis.
The study led to the following notable findings:
- Patients with a BMI of 25 or greater experienced the most significant cardiovascular benefit from GLP-1 RA therapy.
- This group showed a 38% lower risk of cardiovascular death (HR 0.62).
- They also had a 23% lower risk of hospitalization for heart failure (subdistribution HR 0.77) compared with those on DPP-4 inhibitors.
- Kidney outcomes were favorable across both BMI categories, with GLP-1 RAs lowering the risk of kidney function decline and progression to dialysis.
- Restricted cubic spline analysis revealed that cardiovascular benefits became more pronounced with higher BMI.
- The therapy was also linked to reductions in all-cause mortality, infection-related hospitalizations, and overall hospital admissions across all BMI groups.
Despite these promising findings, the authors noted several limitations. Being a retrospective cohort study, risks of residual confounding and selection bias could not be completely ruled out. Additionally, the reliance on a single database means the results may be more representative of the Taiwanese population, and generalizability to other ethnic or healthcare settings remains uncertain.
"GLP-1 RAs were shown to offer BMI-dependent cardiovascular benefits while maintaining consistent kidney protection across body weight categories. These insights highlight the need to factor BMI into treatment strategies for type 2 diabetes and highlight the importance of further randomized clinical trials to confirm these results and explore underlying mechanisms," the authors concluded.
Reference:
Chen T, Hu E, Chen D, et al. GLP-1 RAs and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes. JAMA Netw Open. 2025;8(9):e2530952. doi:10.1001/jamanetworkopen.2025.30952
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