Effects of Dipeptidyl Peptidase-4 Inhibitors and Sulfonylureas on Cognitive and Physical Function in Nursing Home Residents

Aims: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycemia-mediated declines in cognitive and physical functioning compared to sulfonylureas (SUs), yet comparative studies are unavailable among older adults, especially nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. Materials and Methods: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after propensity score matching using Cox regression models. Results: The cohort (N=1,784) had a mean (SD) age of 80 (8) years and was 73% female. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared to SU users, DPP4I users had statistically similar 180-day rates of cognitive decline (HR=0.61, 95%CI 0.31-1.19), altered mental status events (HR=0.71, 95%CI 0.39-1.27), and functional decline (HR=0.89, 95%CI 0.51-1.56). Conclusions: Rates of cognitive and functional decline were not markedly reduced among DPP4I users compared to SU users, but the point estimates and lower 95% confidence bounds do not rule out the possibility that DPP4Is result in reduced rates. Larger studies with greater statistical power should resolve this remaining uncertainty.