| Title: | Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study |
| Journal: | EBioMedicine |
| Published: | 19 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37734206/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2023.104803 |
| URL: | http://www.thelancet.com/article/S2352396423003699/pdf |
Publication 9506
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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).</p>
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.</p>
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.</p>
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.</p>
FUNDING: Funding information is provided in the Acknowledgements.</p>
22 Authors
- Jie Zheng
- Min Xu
- Qian Yang
- Chunyan Hu
- Venexia Walker
- Jieli Lu
- Jiqiu Wang
- Ruixin Liu
- Yu Xu
- Tiange Wang
- Zhiyun Zhao
- Jinqiu Yuan
- Stephen Burgess
- Shiu Lun Au Yeung
- Shan Luo
- Emma L. Anderson
- Michael V. Holmes
- George Davey Smith
- Guang Ning
- Weiqing Wang
- Tom R. Gaunt
- Yufang Bi
1 Application
| Application ID | Title |
|---|---|
| 17295 | AUtomated Generation of Musculoskeletal phENotypes from the UK biobank exTended imaging study (AUGMENT Study) |
Enabling scientific discoveries that improve human health