Association of metformin use with Alzheimer’s disease in patients with newly diagnosed type 2 diabetes: a population-based nested case–control study

• Published in: Scientific reports Vol. 11; no. 1; p. 24069
• Main Authors: Ha, Junghee, Choi, Dong-Woo, Kim, Kwang Joon, Cho, So Yeon, Kim, Hyunjeong, Kim, Keun You, Koh, Youngseung, Nam, Chung Mo, Kim, Eosu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-12-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/92/436/108; 692/699/375/365/1283; Aged; Aged, 80 and over; Alzheimer Disease - epidemiology; Alzheimer Disease - etiology; Alzheimer's disease; Antidiabetics; Biomarkers; Case studies; Case-Control Studies; Cognitive ability; Comorbidity; Dementia disorders; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Disease Susceptibility; Female; Health risks; Humanities and Social Sciences; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Insulin resistance; Male; Metformin; Metformin - adverse effects; Metformin - therapeutic use; multidisciplinary; Neurodegenerative diseases; Population Surveillance; Population-based studies; Risk Assessment; Risk Factors; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-03406-5

Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer’s disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case–control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002–2017). Among 70,499 dementia-free DM patients, 1675 AD cases were matched to 8375 controls for age, sex, and DM onset and duration. The association between AD and metformin was analyzed by multivariable regression analyses, adjusted for comorbidities and cardiometabolic risk profile. Metformin use was associated with an increased odds of AD (adjusted odds ratio [AOR] 1.50; 95% CI 1.23–1.83). The risk of AD was higher in patients with a longer DM duration. Furthermore, AD risk was significantly high in DM patients with depression (AOR 2.05; 95% CI 1.02–4.12). Given the large number of patients with DM who are taking metformin worldwide, a double-blinded, prospective study is required to determine the long-term cognitive safety of metformin.