Key result
Alogliptin linked to ~50% lower risk of moderate-to-severe CKD vs. linagliptin, saxagliptin, and sitagliptin.
Why the study?
The study was conducted to examine kidney disease outcomes associated with individual dipeptidyl peptidase 4 inhibitors (DPP-4i).
Do individual DPP-4 inhibitors differ in their risk of incident moderate-to-severe kidney disease in adults with type 2 diabetes and moderate cardiovascular risk?
Observational (n=171,264)
Yes
Do individual DPP-4 inhibitors differ in their risk of incident moderate-to-severe kidney disease in adults with type 2 diabetes and moderate cardiovascular risk?
In a target trial emulation, alogliptin was associated with a lower risk of incident moderate-to-severe kidney disease compared to other DPP-4 inhibitors in patients with type 2 diabetes.
DPP-4i kidney outcomes in moderate-risk T2D remain uncertain; leaves open whether benefits or harms differ by agent.
OBJECTIVE To examine kidney disease outcomes associated with dipeptidyl peptidase 4 inhibitors (DPP-4i). RESEARCH DESIGN AND METHODS In this target trial emulation, claims data from enrollees in commercial, Medicare Advantage, and traditional Medicare health plans were used to identify adults ≥21 years old with type 2 diabetes, with moderate cardiovascular risk, and without stage 3 or worse chronic kidney disease (CKD) initiating alogliptin, linagliptin, saxagliptin, or sitagliptin between 2014 and 2021. The primary outcome was a composite of incident CKD stages 3–5, kidney failure, or kidney replacement therapy. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method and incorporated as inverse probability of treatment weights into proportional hazards models. RESULTS The weighted study cohort included 3,026 individuals starting alogliptin, 38,213 starting linagliptin, 14,934 starting saxagliptin, and 115,091 starting sitagliptin. One year after treatment initiation, the primary outcome occurred in 1.4%, 2.7%, 2.2%, and 2.4% of patients initiating alogliptin, linagliptin, saxagliptin, and sitagliptin, respectively, increasing to 3.2%, 6.2%, 5.0%, and 5.4%, respectively, at 3 years. Alogliptin was associated with lower risk of stage 3 or worse CKD than linagliptin (hazard ratio [HR] 0.50; 95% CI 0.37–0.69), saxagliptin (HR 0.63; 95% CI 0.45–0.86), and sitagliptin (HR 0.58; 95% CI 0.42–0.79), while saxagliptin was associated with lower risk than linagliptin (HR 0.80; 95% CI 0.73–0.87). Conversely, linagliptin was associated with higher risk than sitagliptin (HR 1.15, 95% CI 1.10–1.21). CONCLUSIONS Alogliptin was associated with lower risk of moderate-to-severe kidney disease than other DPP-4i, while linagliptin was associated with higher risk. Limitations include lack of laboratory data and potential unmeasured confounding.
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Sklepinski et al. (2026) conducted an observational in Type 2 diabetes with moderate cardiovascular risk (n=171,264). Alogliptin vs. Linagliptin was evaluated on Composite of incident CKD stages 3-5, kidney failure, or kidney replacement therapy (HR 0.50, 95% CI 0.37-0.69). Alogliptin was associated with a lower risk of moderate-to-severe kidney disease compared to linagliptin (HR 0.50; 95% CI 0.37-0.69), saxagliptin, and sitagliptin at 3 years.
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