postdoc University of North Carolina at Chapel Hill, Department of Epidemiology Chapel Hill, United States
Background: Previous studies suggested GLP-1 receptor agonists (GLP1RA) may improve cognitive function and liraglutide’s effect on Alzheimer’s disease and related dementia (ADRD) is being evaluated by the ELAD (Evaluating Liraglutide in Alzheimer's Disease) clinical trial.
Objectives: To examine whether liraglutide decrease risk of dementia compared with other antidiabetics in real-world data.
Methods: 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 2010-2019. We required patients to have 2nd prescription of the same drug class and be free of dementia in the 3-year window (during which requiring 3-year continuous enrollment of parts A, B) prior to drug initiation. The dementia outcome was defined as 1) >=1 dementia claims in 1 year AND 2) >=1 dementia claims in another year or nursing home stay >= 6 months in the 3-year follow-up period. A total of 80 covariates were measured in the 1-year baseline period, including demographics, neurological conditions, diabetes comorbidities, cardiovascular comorbidities, other comorbidities, neurological disorder medications and other drug classes, durable medical equipment claims, and measures of healthcare utilization. We estimated propensity scores (PS) to balance confounders across cohorts, and applied asymmetric PS trimming using a cut point corresponding to the 5th and 95th percentiles of the PS distribution in the treated and untreated patients, respectively. We estimated adjusted risk difference (RD) and 95% CI using inverse probability treatment weight.
Results: 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 3-year follow-up, incident cases of dementia 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.
Conclusions: Our active comparator, new user cohort study of older patients showed liraglutide is associated with a decreased risk of dementia compared with alternatives. This study is limited by the relatively short duration of treatments.
