Liraglutide as a potential drug repurposing candidate for Alzheimer’s disease and related dementia: Real World Evidence

Abstract Background Previous studies suggested GLP‐1 receptor agonists (GLP1RA) may improve cognitive function and liraglutide’s effect on Alzheimer’s disease is being evaluated by the ELAD (Evaluating Liraglutide in Alzheimer’s Disease) clinical trial. Method To examine whether liraglutide decrease Alzheimer’s disease and related dementia ( ADRD) risk compared with other antidiabetics, we implemented an active comparator, new user cohort design identifying initiators of liraglutide, DPP‐4 inhibitors (DPP4i), respectively, using a US nationwide 20% random sample of fee‐for‐service Medicare beneficiaries aged 70+ with parts A, B, and D coverage from 2007‐2019. We required patients to have 2nd prescription of the same drug class and be free of ADRD in the 3‐year window (during which requiring 3‐year continuous enrollment of parts A, B) prior to drug initiation. The ADRD outcome was defined as 1) ³1 ADRD claims in 1 year AND 2) ³1 ADRD claims in another year or nursing home stay ³ 6 months in the 3‐year follow‐up period. We estimated propensity scores (PS) to balance confounders across cohorts and estimated adjusted risk difference (RD) and 95% CI using inverse probability treatment and censoring weight. Result The initiators of liraglutide (n = 1260) and DPP4i (n = 15952) were followed for a median (IQR) duration of 3.0(2.0 to 3.0) and 3.0 (1.7 to 3.0) years, respectively. During follow‐up, incident cases of ADRD was 196 and 3215 in liraglutide and DPP4i, respectively; and incident rate was 63 and 85 per 1000 person‐years, respectively. Adjusted RD (%) was ‐4.4 (95%CI ‐6.6 to ‐2.39) comparing liraglutide to DPP4i. Results were consistent across sensitivity analyses with varying exclusion criteria, baseline period, and outcome definitions. Conclusion Our active comparator, new user cohort study of older patients showed liraglutide is associated with a decreased ADRD risk compared with alternatives. This study is limited by the relatively short duration of treatments.