In diabetes patients with worsening kidney disease, liraglutide users saw a significant rise in cardiovascular events while dulaglutide users did not, suggesting dulaglutide may be the better choice for patients with advanced CKD.
HR 4.078Liraglutide's MACE hazard ratio in diabetes patients with eGFR <60, vs. no significant increase with dulaglutide
What the researchers found
Among 1,572 T2DM patients (945 liraglutide, 627 dulaglutide), there was no overall significant difference in MACE between the two drugs. However, liraglutide users showed a significant increase in MACE with worsening kidney function:
- eGFR 60–89: HR 1.401 (95% CI 0.663–2.958)
- eGFR <60: HR 4.078 (95% CI 1.111–14.971, P = 0.0079)
This trend was not observed with dulaglutide (P = 0.1906), suggesting dulaglutide may maintain cardiovascular protection across CKD stages while liraglutide's benefit diminishes with declining renal function.
Why it matters
Many diabetes patients also have chronic kidney disease, and choosing the right GLP-1 receptor agonist for these patients is clinically important. This study suggests the choice between liraglutide and dulaglutide may matter more than previously thought, particularly for patients with advancing kidney disease.
How the study worked
Retrospective analysis of 362,842 T2DM patients from the Chang Gung Research Database (Taiwan, 2011–2019). After exclusion criteria, 1,572 GLP-1 RA users were included. MACE incidence was compared between liraglutide and dulaglutide across CKD stages. Secondary outcomes included kidney function deterioration, renal disease, UTIs, pancreatitis, amputations, and cancers.
What this study cannot tell us
This is a retrospective observational study from a single healthcare system in Taiwan, limiting generalizability. The sample sizes in advanced CKD subgroups were small, leading to wide confidence intervals. The study could not control for all confounders, and the reason for the differential CKD interaction is unclear. It does not include newer agents like semaglutide or tirzepatide.
How to read the evidence
This is a retrospective cohort study from a large healthcare database. While it provides real-world data on a clinically important question, it's observational and cannot establish causation. Small subgroup sizes in advanced CKD limit the reliability of the findings.
When this study was published
Published in 2025 in Endocrine Practice, using data from 2011–2019. The findings are relevant to current prescribing, though newer GLP-1 RAs were not included.
The bigger picture
GLP-1 receptor agonists are increasingly used not just for glucose control but for cardiovascular and renal protection. This study raises the important question of whether all GLP-1 RAs are equally effective across different patient populations, or whether specific drugs may be better suited for specific comorbidity profiles.
Questions still open
- What pharmacological differences between liraglutide and dulaglutide explain the divergent cardiovascular outcomes in advanced CKD?
- Would semaglutide or tirzepatide show a similar or different pattern across CKD stages?
- Should CKD stage influence which GLP-1 receptor agonist is prescribed to diabetes patients?
Common questions
Should I switch from liraglutide to dulaglutide if I have kidney problems?
Why might these two GLP-1 drugs work differently in kidney disease?
Read the original research
The Cardiovascular Outcomes Between Liraglutide and Dulaglutide Among Different Chronic Kidney Disease Stages in Patients With Type 2 Diabetes.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(3), 292-297
Citation
Cai, Yu-Xuan; Liu, Feng-Hsuan; Sun, Jui-Hung; Lin, Chia-Hung. (2025). The Cardiovascular Outcomes Between Liraglutide and Dulaglutide Among Different Chronic Kidney Disease Stages in Patients With Type 2 Diabetes.. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 31(3), 292-297. https://doi.org/10.1016/j.eprac.2024.11.016