Semaglutide May Offer Greater Kidney Protection Among GLP-1 RAs in diabetes patients: Study

To properly evaluate the intra-class variations without conducting any direct head-to-head randomized trials, the researchers conducted a retrospective observational study making use of administrative claims data from the OptumLabs Data Warehouse database and 100% Medicare fee-for-service claims. The study population was made up of adults aged 21 years and older with T2DM and moderate cardiovascular risk who had newly prescribed one of dulaglutide, exenatide, liraglutide, or semaglutide from January 1, 2019, to December 31, 2021.

To simulate randomization and reduce any potential bias in the assignment process, the researchers applied inverse probability of treatment weights (IPTWs) that were calculated from the SuperLearner algorithm. Analysis of time-to-event outcomes considered the following two composite kidney outcomes: the primary composite kidney outcome (incident CKD stages 3–4 and kidney failure, which includes CKD stage 5 or kidney replacement therapy) and the secondary composite kidney outcome (primary renal outcomes plus all-cause mortality).

Key findings:

• Statistically significant differences between the treatments of interest with regard to the primary kidney composite outcome of incident CKD stage 3-4 and kidney failure were not found.
• The statistical analysis showed that semaglutide therapy was associated with statistically significantly lower risk of the secondary composite kidney outcome (including all-cause mortality) than dulaglutide (hazard ratio [HR] = 0.92; 95% CI, 0.87-0.97).
• The risk of the secondary composite kidney outcome was 12% lower with initiation of semaglutide therapy as compared to exenatide treatment (HR = 0.88; 95% CI, 0.79-0.99).
• In isolation analysis, it has been revealed that semaglutide treatment was associated with statistically significantly 19% lower risk of all-cause mortality than dulaglutide treatment (HR = 0.81; 95% CI, 0.70-0.93).
• Limitations of the study include possible confounding by the unmeasured clinical factors, absence of laboratory data on hemoglobin A1c and body weight at the baseline, and unclear indication for drug prescription.

It can be concluded that while each GLP-1 receptor agonist exhibits similar efficacy for primary incident chronic kidney disease cases, semaglutide is associated with substantial benefits concerning secondary composite renal outcomes and all-cause mortality. The results of the study indicate that semaglutide might be considered the optimal choice of GLP-1 receptor agonist in order to postpone renal complications and prolong life expectancy of individuals with type 2 diabetes mellitus and moderate cardiovascular risk.

Reference:

Neumiller, J. J., Deng, Y., Swarna, K. S., Polley, E. C., Herrin, J., Galindo, R. J., Umpierrez, G. E., Ross, J. S., Mickelson, M. M., Dryden, K., Tuttle, K. R., & McCoy, R. G. (2026). Comparison of Specific Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes Among Patients With Type 2 Diabetes. American Journal of Kidney Diseases, 88(3), 366–377. https://doi.org/10.1053/j.ajkd.2026.04.007