Dataset Information

Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

ABSTRACT: Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

SUBMITTER: Akimoto H

PROVIDER: S-EPMC11005324 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

Akimoto Hayato H Negishi Akio A Oshima Shinji S Wakiyama Haruna H Okita Mitsuyoshi M Horii Norimitsu N Inoue Naoko N Ohshima Shigeru S Kobayashi Daisuke D

American journal of Alzheimer's disease and other dementias 20200101

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapi ...[more]

PMID: 32162525

Similar Datasets

Project description:Background and objectivesPrevious studies have highlighted antidiabetic drugs as repurposing candidates for Alzheimer disease (AD), but the disease-modifying effects are still unclear.MethodsA 2-sample mendelian randomization study design was applied to examine the association between genetic variation in the targets of 4 antidiabetic drug classes and AD risk. Genetic summary statistics for blood glucose were analyzed using UK Biobank data of 326,885 participants, whereas summary statistics for AD were retrieved from previous genome-wide association studies comprising 24,087 clinically diagnosed AD cases and 55,058 controls. Positive control analysis on type 2 diabetes mellitus (T2DM), insulin secretion, insulin resistance, and obesity-related traits was conducted to validate the selection of instrumental variables.ResultsIn the positive control analysis, genetic variation in sulfonylurea targets was associated with higher insulin secretion, a lower risk of T2DM, and an increment in body mass index, waist circumference, and hip circumference, consistent with drug mechanistic actions and previous trial evidence. In the primary analysis, genetic variation in sulfonylurea targets was associated with a lower risk of AD (odds ratio [OR] = 0.38 per 1 mmol/L decrement in blood glucose, 95% CI 0.19-0.72, p = 0.0034). These results for sulfonylureas were largely unchanged in the sensitivity analysis using a genetic variant, rs757110, that has been validated to modulate the target proteins of sulfonylureas (OR = 0.35 per 1 mmol/L decrement in blood glucose, 95% CI 0.15-0.82, p = 0.016). An association between genetic variations in the glucagon-like peptide 1 (GLP-1) analogue target and a lower risk of AD was also observed (OR = 0.32 per 1 mmol/L decrement in blood glucose, 95% CI 0.13-0.79, p = 0.014). However, this result should be interpreted with caution because the positive control analyses for GLP-1 analogues did not comply with a weight-loss effect as shown in previous clinical trials. Results regarding other drug classes were inconclusive.DiscussionGenetic variation in sulfonylurea targets was associated with a lower risk of AD, and future studies are warranted to clarify the underlying mechanistic pathways between sulfonylureas and AD.

Project description:Peripheral artery disease (PAD) is an atherosclerotic condition commonly complicating type 2 diabetes (T2D), leading to poor quality of life and increased risk of major adverse lower-limb (MALE) and cardiovascular (CV) events (MACE). Therapeutic management of PAD in T2D patients is much more arduous, often due to bilateral, multi-vessel, and distal vascular involvement, in addition to increased systemic polyvascular atherosclerotic burden. On the other hand, the pathophysiological link between PAD and T2D is very complex, involving mechanisms such as endothelial dysfunction and increased subclinical inflammation in addition to chronic hyperglycemia. Therefore, the clinical approach should not ignore vascular protection with the aim of reducing limb and overall CV events besides a mere glucose-lowering effect. However, the choice of the best medications in this setting is challenging due to low-grade evidence or lacking targeted studies in PAD patients. The present review highlighted the strong relationship between T2D and PAD, focusing on the best treatment strategy to reduce CV risk and prevent PAD occurrence and worsening in patients with T2D. The Medline databases were searched for studies including T2D and PAD up to June 2024 and reporting the CV effectiveness and safety of the most used glucose-lowering agents, with no restriction on PAD definition, study design, or country. The main outcomes considered were MACE-including nonfatal acute myocardial infarction, nonfatal stroke, and CV death-and MALE-defined as lower-limb complications, amputations, or need for revascularization. To the best of our current knowledge, GLP-1 receptor agonists and SGLT2 inhibitors represent the best choice to reduce CV risk in T2D and PAD settings, but a personalized approach should be considered. GLP-1 receptor agonists should be preferred in subjects with prevalent atherosclerotic burden and a history of previous MALE, while SGLT2 inhibitors should be used in those with heart failure if overall CV benefits outweigh the risk of lower-limb complications.

Dataset Information

Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

Publications

Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets