Comparison of Specific Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes Among Patients With Type 2 Diabetes

RATIONALE & OBJECTIVE Glucagon-like peptide-1 (GLP-1) receptor agonist treatment is associated with lower risk for incident chronic kidney disease (CKD) and death relative to treatment with a dipeptidyl peptidase-4 inhibitor or sulfonylurea. This study examined within class effects of GLP-1 receptor agonists on kidney outcomes in type 2 diabetes (T2D) and moderate cardiovascular risk. STUDY DESIGN Retrospective observational study using the target trial emulation framework. SETTING & PARTICIPANTS This study used claims data from OptumLabs® Data Warehouse and 100% sample of Medicare fee-for-service claims. Participants were adults ≥21 years of age, at moderate cardiovascular risk, who filled a new prescription for a GLP-1 receptor agonists between January 1, 2019 and December 31, 2021. EXPOSURE GLP-1 receptor agonists dulaglutide, exenatide, liraglutide, or semaglutide. OUTCOMES A primary kidney composite outcome inclusive of incident diagnosis codes for CKD stages 3-4 and kidney failure (inclusive of CKD stage 5 and kidney replacement therapy). A secondary kidney composite outcome included the elements of the primary composite outcome plus death from any cause. Components of the kidney composite outcomes were also evaluated independently. ANALYTICAL APPROACH Random treatment assignment was emulated using inverse probability of treatment weighting (IPTW) with propensity scores estimated using the SuperLearner ensemble method. Primary analyses were time-to-event models under the intention-to-treat framework using cause-specific IPTW Cox proportional hazards models. RESULTS There was no difference among dulaglutide, exenatide, liraglutide, and semaglutide with respect to the primary outcome. When compared to dulaglutide and exenatide, semaglutide was associated with a reduced risk for the secondary kidney composite outcome by 8% (HR 0.92 [95% CI, 0.87-0.97]) and 12% (HR:0.88; 95% CI: 0.79-0.99), respectively. Compared to dulaglutide, semaglutide was also associated with reduced risk of death (HR 0.81 [95% CI, 0.70-0.93]). LIMITATIONS Potential for residual confounding, lack of HbA1c and weight data, and uncertainty about the indication for GLP-1 receptor agonist prescriptions. CONCLUSIONS No differences were observed among different GLP-1 receptor agonists for the primary outcome, but semaglutide initiation was associated with a lower risk of the secondary kidney composite outcome and of death. PLAIN-LANGUAGE SUMMARY Chronic kidney disease (CKD) is a common complication of diabetes that increases the risk for poor health outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists were found to improve kidney outcomes in people with type 2 diabetes (T2D) and moderate cardiovascular risk when compared to dipeptidyl peptidase-4 inhibitors and sulfonylureas. While there has been no head-to-head comparison of individual GLP-1 receptor agonists, randomized controlled trials suggest that there may be variation among members of this drug class on kidney disease outcomes. In this study, we tested whether there were differences in kidney outcomes when comparing individual GLP-1 receptor agonist medications. We found that semaglutide compared favorably to other drugs in the class and may represent the preferred GLP-1 receptor agonist for delaying or preventing CKD in this population.