Key result
GLP-1 RAs linked to ~16% lower MAKE risk vs DPP-4is in diabetic kidney disease.
Why the study?
Do GLP-1 receptor agonists reduce cardiorenal events and mortality in adults with T2DM and CKD stages 2-4 compared to DPP-4 inhibitors?
Cohort (n=57,648)
Yes
Do GLP-1 receptor agonists reduce cardiorenal events and mortality in adults with T2DM and CKD stages 2-4 compared to DPP-4 inhibitors?
Hazard Ratio: 0.837 (95% CI 0.796–0.88)
p-value: p=<.001
In a real-world cohort of patients with T2DM and CKD stages 2-4, GLP-1 RA initiation was associated with significantly lower risks of major adverse kidney events, cardiovascular events, and mortality compared with DPP-4i.
Patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) face compounded cardiorenal risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and renal benefits in randomized trials, yet real-world evidence in populations with established CKD stages 2 through 4 remains limited. We aimed to compare cardiorenal outcomes between new users of GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4i) in this high-risk population. Using the TriNetX Global Collaborative Network, we conducted a new-user, active-comparator cohort study emulating a target trial. Adults with T2DM and CKD stages 2–4 who initiated GLP-1 RA or DPP-4i between January 2017 and December 2021 were identified. After 1:1 propensity score matching on 40 covariates, 28,824 patients per group were retained. Three co-primary outcomes—MAKE, MACE, and all-cause mortality—were assessed at 1, 2, and 3 years from the same matched cohort. Secondary outcomes included a safety composite and hypoglycemia. Conjunctivitis served as a negative control outcome. Restricted mean survival time was calculated as a supplementary analysis. At 3 years, GLP-1 RA initiation was associated with significantly lower risks of MAKE (hazard ratio [HR] 0.837; 95% confidence interval [CI] 0.796–0.880; P < .001), MACE (HR 0.875; 95% CI 0.843–0.909; P < .001), and all-cause mortality (HR 0.787; 95% CI 0.743–0.834; P < .001) compared with DPP-4i. These associations were evident at 1 year and persisted through 3 years. The safety composite favored GLP-1 RAs (HR 0.905; 95% CI 0.877–0.934; P < .001), with comparable hypoglycemia rates between groups. The negative control outcome yielded null results (HR 0.959; 95% CI 0.865–1.065; P = .436), supporting the validity of the study design. In this large, propensity score–matched, international real-world cohort, GLP-1 RA initiation was associated with significantly lower risks of adverse kidney events, cardiovascular events, and mortality compared with DPP-4i in patients with T2DM and CKD stages 2 through 4. Benefits emerged early and persisted over 3 years, providing supportive evidence for GLP-1 RAs to a population underrepresented in randomized trials.
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Chen et al. (2026) conducted a cohort in Type 2 diabetes mellitus with CKD stages 2-4 (n=57,648). GLP-1 receptor agonists vs. Dipeptidyl peptidase-4 inhibitors (DPP-4i) was evaluated on MAKE (co-primary outcome) (HR 0.837, 95% CI 0.796-0.880, p=<.001). GLP-1 RA initiation was associated with lower risks of MAKE (HR 0.837; 95% CI 0.796-0.880; P<.001), MACE, and mortality compared with DPP-4i in adults with T2DM and CKD stages 2-4 at 3 years.
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