Zheng, Jie;
Xu, Min;
Yang, Qian;
Hu, Chunyan;
Walker, Venexia;
Lu, Jieli;
Wang, Jiqiu;
... Bi, Yufang; + view all
(2023)
Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study.
EBioMedicine
, 96
, Article 104803. 10.1016/j.ebiom.2023.104803.
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Abstract
BACKGROUND: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). METHODS: Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. FINDINGS: Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46-0.84), lower levels of body mass index (BMI) (β = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (β = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (β = -0.29, 95% CI = -0.39 to -0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. INTERPRETATION: This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. FUNDING: Funding information is provided in the Acknowledgements.
| Type: | Article |
|---|---|
| Title: | Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2023.104803 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2023.104803 |
| Language: | English |
| Additional information: | Copyright © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Cardiometabolic diseases, General population, Mendelian randomization, Metformin targets, Non-diabetic individuals |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health of Older People |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10177628 |
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