GLP-1 RAs Linked to BMI-Dependent Heart Benefits in Type 2 Diabetes

New research from Taiwan suggests that the cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) vary by body mass index (BMI).1 In a study comparing GLP-1 RAs with dipeptidyl peptidase-4 (DPP-4) inhibitors, investigators found that patients with higher BMIs saw greater reductions in cardiovascular (CV) death and heart failure, while kidney protection remained consistent across all BMI categories.

This retrospective cohort study is published in JAMA Network Open.

A study finds stronger cardiovascular protection from glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with higher body mass index (BMI), with kidney benefits consistent across all groups. | Image credit: Vitalii Vodolazskyi - stock.adobe.com

“To our knowledge, this cohort study is the first study focusing on the differential outcomes associated with GLP-1 RAs based on BMI,” wrote the researchers of the study. “In this large retrospective cohort study, we found that GLP-1 RAs were associated with significantly lower CV risk in patients with type 2 diabetes and BMI 25 or more compared with matched patients using DPP-4 inhibitors. Meanwhile, the protective associations of GLP-1 RAs for kidney outcomes were consistent across all BMI categories. These findings suggest a potential interaction between BMI and CV—but not kidney—benefits of GLP-1 RAs.”

Diabetes continues to be a major global health challenge, with the International Diabetes Federation’s 11th Diabetes Atlas estimating that nearly 589 million people worldwide are currently living with the condition.2 Alarmingly, more than 250 million individuals remain undiagnosed, leaving them especially vulnerable to serious complications and premature death. With nearly 1 in 9 adults affected, the growing burden of diabetes underscores the urgent need for improved awareness, early detection, and equitable access to care to reduce its long-term health and societal impact.

The study included data from multiple hospitals in Taiwan of patients with T2D who initiated treatment with either GLP-1 RAs or DPP-4 inhibitors between 2011 and 2022.1 DPP-4 inhibitors were selected as the comparator because of their widespread use as a second-line therapy and their relatively neutral cardiovascular and kidney effects. Patients were stratified into 2 groups based on BMI: below 25 and 25 or higher. Outcomes were assessed from December 15, 2023, to July 5, 2024.

Among 97,156 patients with T2D identified, 7200 matched patients were included in the analysis. In patients with higher BMI, initiation of GLP-1 RAs was associated with significantly lower risks of CV death (HR, 0.62; 95% CI, 0.46-0.83) and hospitalization for heart failure (subdistribution HR, 0.77; 95% CI, 0.62-0.94) compared with DPP-4 inhibitors.

Kidney outcomes were consistent across BMI categories. Additional analysis further indicated that the CV benefits of GLP-1 RAs increased with higher BMI, underscoring a BMI-dependent relationship in treatment response.

However, the researchers noted some limitations, such as its nonrandomized design, which may have introduced bias and unmeasured confounding. Additionally, the findings, which were based on data from Taiwan’s Chang Gung Research Database, may not be generalizable to other populations or care settings.

Despite these limitations, the researchers believe the study highlights the potential value of BMI-based treatment decisions in diabetes care.

"In this cohort study of patients with type 2 diabetes, the CV benefits associated with GLP-1 RAs were BMI-dependent, with significant reductions in CV death and heart failure hospitalization observed only in patients with BMI 25 or greater," wrote the researchers. "In contrast, GLP-1 RAs demonstrated consistent kidney protective associations regardless of BMI, reducing the risk of eGFR decline and progression to dialysis in both BMI groups. Furthermore, GLP-1 RAs were associated with reduced all-cause mortality, infection-related hospitalizations, and all-cause hospitalizations across all BMI categories."

References

1. Chen TH, Hu EH, Chen DI, 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

2. Steinzor P. More than 250 million individuals unaware they have diabetes. AJMC®. April 7, 2025. Accessed September 8, 2025. https://www.ajmc.com/view/more-than-250-million-individuals-unaware-they-have-diabetes