Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes.

TitleUse of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes.
Publication TypeJournal Article
Year of Publication2022
AuthorsTang X, Brinton RDiaz, Chen Z, Farland LV, Klimentidis Y, Migrino R, Reaven P, Rodgers K, Zhou JJ
JournalBMJ Open Diabetes Res Care
Date Published2022 Sep
KeywordsAged, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Humans, Hypoglycemic Agents, Metformin, Retrospective Studies, Sulfonylurea Compounds, Thiazolidinediones, Treatment Outcome, Veterans

INTRODUCTION: Studies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET).

RESEARCH DESIGN AND METHODS: This is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer's disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models.

RESULTS: Among 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15).

CONCLUSIONS: Among patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia.

Alternate JournalBMJ Open Diabetes Res Care
PubMed ID36220195
PubMed Central IDPMC9472121
Grant ListR01 HG006139 / HG / NHGRI NIH HHS / United States
K01 DK106116 / DK / NIDDK NIH HHS / United States
R21 HL150374 / HL / NHLBI NIH HHS / United States
R21 HL150268 / HL / NHLBI NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D
Kathleen Rodgers, Ph.D.