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Article: Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study

TitleEfficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study
Authors
KeywordsCardiometabolic diseases
General population
Mendelian randomization
Metformin targets
Non-diabetic individuals
Issue Date19-Sep-2023
PublisherElsevier
Citation
EBioMedicine, 2023, v. 96 How to Cite?
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) (beta = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (beta = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (beta = -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.


Persistent Identifierhttp://hdl.handle.net/10722/340456
ISSN
2022 Impact Factor: 11.1
2020 SCImago Journal Rankings: 2.596
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, Jie-
dc.contributor.authorXu, Min-
dc.contributor.authorYang, Qian-
dc.contributor.authorHu, Chunyan-
dc.contributor.authorWalker, Venexia-
dc.contributor.authorLu, Jieli-
dc.contributor.authorWang, Jiqiu-
dc.contributor.authorLiu, Ruixin-
dc.contributor.authorXu, Yu-
dc.contributor.authorWang, Tiange-
dc.contributor.authorZhao, Zhiyun-
dc.contributor.authorYuan, Jinqiu-
dc.contributor.authorBurgess, Stephen-
dc.contributor.authorAu Yeung, Shiu Lun-
dc.contributor.authorLuo, Shan-
dc.contributor.authorAnderson, Emma L-
dc.contributor.authorHolmes, Michael V-
dc.contributor.authorSmith, George Davey-
dc.contributor.authorNing, Guang-
dc.contributor.authorWang, Weiqing-
dc.contributor.authorGaunt, Tom R-
dc.contributor.authorBi, Yufang-
dc.date.accessioned2024-03-11T10:44:47Z-
dc.date.available2024-03-11T10:44:47Z-
dc.date.issued2023-09-19-
dc.identifier.citationEBioMedicine, 2023, v. 96-
dc.identifier.issn2352-3964-
dc.identifier.urihttp://hdl.handle.net/10722/340456-
dc.description.abstract<p>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) (beta = -0.22, 95% CI = -0.35 to -0.09), systolic blood pressure (SBP) (beta = -0.19, 95% CI = -0.28 to -0.09) and diastolic blood pressure (DBP) levels (beta = -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.<br></p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofEBioMedicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCardiometabolic diseases-
dc.subjectGeneral population-
dc.subjectMendelian randomization-
dc.subjectMetformin targets-
dc.subjectNon-diabetic individuals-
dc.titleEfficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study-
dc.typeArticle-
dc.identifier.doi10.1016/j.ebiom.2023.104803-
dc.identifier.scopuseid_2-s2.0-85171469943-
dc.identifier.volume96-
dc.identifier.eissn2352-3964-
dc.identifier.isiWOS:001082190600001-
dc.identifier.issnl2352-3964-

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