GLP1s vs DPP4s and Risk of Dementia in Patients Requiring Hemodialysis, A Target Trial Emulation Study

<p dir="ltr"><u>Objective:</u><br>Glucagon-like peptide-1 agonists (GLP1s) (versus dipeptidyl peptidase-4 inhibitors [DPP4s]) are associated with reduced risk of dementia in the general population with diabetes, but if this association is true for patients requiring hemodialysis is unknown.</p><p><br></p><p dir="ltr"><u>Research Design and Methods:</u><br>Using the United States Renal Data System and Medicare Parts A, B, and D claims data from 2011 to 2021, we used the active comparator, new-user design to evaluate incident dementia comparing GLP1s vs DPP4s among individuals with both diabetes and hemodialysis dependence. We used inverse probability of treatment weights (IPTW) to balance baseline characteristics and Fine-Gray models to estimate sub-distribution hazard ratios [sHRs] accounting for competing risks of death and kidney transplantation. We estimated intention-to-treat and as-treated effects.</p><p><br></p><p dir="ltr"><u>Results:</u>We identified 3,619 GLP1 users and 11,502 DPP4 users. After IPTW, the average individual was 63 years old, 63% were white, and mean BMI was 31 kg/m². <a href="" target="_blank">The median (interquartile interval) follow-up was </a>1.5 (0.6 - 2.9) years, and 2,014 patients received a dementia diagnosis. In the intention-to-treat analysis, the IPTW-sHR for dementia was 0.82 (95% CI: 0.67 - 0.98), and <a href="" target="_blank">after 2 years of follow-up, the cumulative incidence of dementia was 10.2% on GLP1s vs 11.2% on DPP4s. As-treated and subgroup analyses were consistent. GLP1s were also associated with an increased risk of ketoacidosis (sHR 1.52, 95% CI: 1.14 – 2.02; 2-year cumulative incidence: 3.1% vs 2.2%).</a></p><p><br></p><p dir="ltr"><u>Conclusions:</u><br>In patients with diabetes requiring hemodialysis, GLP1s (vs DPP4s) may be a promising therapy to reduce the risk of dementia.</p>