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. 2025 Sep 2;8(9):e2530952.
doi: 10.1001/jamanetworkopen.2025.30952.

GLP-1 RAs and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes

Tien-Hsing Chen  1   2   3 , En-Hao Hu  4   2 , Dong-Yi Chen  5   2 , Yuan Lin  6   2 , Tien-Shin Chou  7   2 , Ming-Shyan Lin  8   2 , Ning-I Yang  1   2 , Chao-Yung Wang  5   2 , Ming-Jui Hung  1   2 , Ming-Lung Tsai  9   2   10
Affiliations

GLP-1 RAs and Cardiovascular and Kidney Outcomes by Body Mass Index in Type 2 Diabetes

Tien-Hsing Chen et al. JAMA Netw Open. .

Abstract

Importance: The cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may vary by body mass index (BMI), but evidence on BMI-specific outcomes remains limited.

Objective: To investigate the associations of GLP-1 RA use with cardiovascular and kidney outcomes across BMI categories in patients with type 2 diabetes.

Design, setting, and participants: This retrospective cohort study used the Chang Gung Research Database, a clinical dataset covering multiple hospitals in Taiwan. Patients with type 2 diabetes who received GLP-1 RAs or dipeptidyl peptidase-4 (DPP-4) inhibitors between 2011 and 2022 were identified. DPP-4 inhibitors were selected as the comparator due to their widespread use as a second-line oral hypoglycemic agent and their relatively neutral cardiovascular and kidney effects reported in previous studies. Propensity score matching was applied separately within BMI categories less than 25 and 25 or greater using a comprehensive set of demographic, clinical, and biochemical variables to balance baseline characteristics between treatment groups. The analysis was conducted from December 15, 2023, to July 5, 2024.

Exposures: Initiation of GLP-1 RAs compared with DPP-4 inhibitors.

Main outcomes and measures: Primary outcomes included major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, ischemic stroke, or hospitalization for heart failure) and composite kidney outcomes (defined as estimated glomerular filtration rate decline ≥50% or progression to dialysis).

Results: Among 97 156 patients with diabetes identified, a total of 7200 matched patients (mean [SD] age, 57.4 [14.2] years; 7473 [51.9%] female) were included (1841 pairs with BMI <25 and 5359 pairs with BMI ≥25). Among patients with BMI 25 or greater, GLP-1 RAs were associated with lower risks of cardiovascular death (hazard ratio [HR], 0.62; 95% CI, 0.46-0.83) and hospitalization for heart failure (subdistribution HR, 0.77; 95% CI, 0.62-0.94). Kidney outcomes were consistent across BMI strata. Restricted cubic spline analysis revealed increasing cardiovascular benefit associated with GLP-1 RAs among patients with higher BMI.

Conclusions and relevance: In this cohort study of patients with type 2 diabetes, GLP-1 RAs use was associated with BMI-dependent cardiovascular benefits and consistent kidney protection, suggesting the importance of BMI stratification in guiding treatment decisions.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Flow of Patient Inclusion and Exclusion
BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); DPP4i, DPP-4 inhibitors; EF, ejection fraction; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated hemoglobin A1c; SLGT2i, sodium–glucose cotransporter 2 inhibitor.
Figure 2.
Figure 2.. Cumulative Cardiovascular and Kidney Outcomes in the Propensity Score–Matched Cohort
BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); DPP4i, DPP-4 inhibitor; GLP-1 RA, glucagon-like peptide-1 receptor agonist.
Figure 3.
Figure 3.. Restricted Cubic Spline Analysis of Body Mass Index Thresholds for Optimal Benefits From Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs)
Body mass index is calculated as weight in kilograms divided by height in meters squared. HR indicates hazard ratio.
See this image and copyright information in PMC

Comment in

  • doi: 10.1001/jamanetworkopen.2025.30969

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