Dataset Information

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

ABSTRACT:

Introduction

Little is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D).

Methods

Participants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005-2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model.

Results

Among 1393 participants, 104 developed dementia over a 4-year median follow-up. Metformin was significantly associated with a lower risk of dementia in the overall population (RD, -3.2%; 95% CI, -6.2% to -0.2%). We identified four subgroups with varied risks for dementia, defined by neuropsychiatric disorders, non-steroidal anti-inflammatory drugs, and antidepressant use.

Discussion

Metformin use was significantly associated with a lower risk of dementia in individuals with T2D, with significant variability among subgroups.

SUBMITTER: Tang H

PROVIDER: S-EPMC10917005 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

Tang Huilin H Guo Jingchuan J Shaaban C Elizabeth CE Feng Zheng Z Wu Yonghui Y Magoc Tanja T Hu Xia X Donahoo William T WT DeKosky Steven T ST Bian Jiang J

Alzheimer's & dementia : the journal of the Alzheimer's Association 20231013 2

<h4>Introduction</h4>Little is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D).<h4>Methods</h4>Participants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005-2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall p ...[more]

PMID: 37830443

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Project description:AimsIn observational studies, type-2 diabetes is associated with increased risk of dementia; however, the causal nature of this association remains unanswered. In an unselected nationwide study of all Danes, we wanted to test whether type-2 diabetes is associated with dementia subtypes, and to test whether potential associations are of a causal nature.MethodsIn the current study of nationwide observational registry data in all Danes above the age of 65 years (n = 784 434) combined with genetic consortia data on 213 370 individuals, we investigated the associations between type-2 diabetes and Alzheimer's disease, vascular dementia, unspecified dementia and all-cause dementia, and whether observational associations were of a causal nature by applying a two-sample Mendelian randomisation strategy. We addressed key biases inherent in Mendelian randomisation approaches.ResultsImportant confounders (age, ethnicity, size of community, region, civil status and education level) were captured on all 784 434 individuals and adjusted for in the models. Multifactorial adjusted hazard ratios were 1.13 (1.06-1.21) for Alzheimer's disease, 1.98 (1.83-2.14) for vascular dementia, 1.53 (1.48-1.59) for unspecified dementia and 1.48 (1.44-1.53) for all-cause dementia in persons with type-2 diabetes v. without. Results were similar for men and women. The two-sample Mendelian randomisation estimate for the association between the genetic instrument and Alzheimer's disease was 1.04 (0.98-1.10), consistent with sensitivity estimates, addressing pleiotropy, measurement bias and weak instrument bias.ConclusionsIn a nationwide study of all Danes above the age of 65 years, we show that type-2 diabetes is associated with major subtypes of dementia - with particularly strong associations for vascular dementia and unspecified dementia - the two types of dementia with the most obvious vascular pathologies. Although the present two-sample Mendelian randomisation approach using genetic consortia data suggests that type-2 diabetes is not a direct cause of Alzheimer's disease, we were unable to test the causal nature of type-2 diabetes for vascular dementia and unspecified dementia, because no publicly available genetic consortia data yet exist for these dementia endpoints. The causal nature of type-2 diabetes for dementia with vascular pathologies is pivotal questions to solve for future public health recommendations and therapeutic advice.

Project description:BackgroundMetformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China.MethodsAll patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.ResultsAmong 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0 g and >2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69).ConclusionsIn Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.

Dataset Information

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

Introduction

Methods

Results

Discussion

Publications

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

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