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Using Mendelian randomization, our study suggests that activation of adenosine monophosphate-activated protein kinase (AMPK), one of the targets of metformin, may reduce type 2 diabetes, coronary artery disease and overall cancer risk. Whether metformin can be repurposed for the prevention of these diseases should be further explored. We believe the study may generate some discussion in the scientific communities as metformin's anti-cancer property has been controversial.
Using Mendelian randomization to infer health effects of cardiovascular and diabetes medication in the UK Biobank
Aim of the study
The aim of this study is to use genetics to evaluate the health impact of medication commonly used in cardiovascular disease and diabetes
Randomized controlled trials (RCTs) are the gold standard in evaluating the health effects of medication. However, conducting RCTs may expose participants to unexpected risk, especially when there have been concerns over the validity of the evidence on the putative effect of medications (e.g. biases). As such, this may pose substantial ethical issues for whether such trials should be conducted, apart from the resources required to conduct such trials.
To facilitate the discovery/repurposing of medications for treatment of other diseases, alternative methods are being development such as the use of genomics. The use of genetics has been shown to produce results comparable to randomized controlled trials regarding the health effects of medication. Wider use of this approach may help verify the health effects of medications before they are being tested in an RCT setting.
The UK Biobank is one of the most appropriate epidemiologic sources to address this issue given it is one of the largest cohort studies globally, having access to comprehensive health data, and in-depth genetic data. Such combination would allow ascertainment of various medications' impact on health in a cost effective manner and help identify potential existing medications to be repurposed for treatment of other diseases (e.g genetic validation).
Public health impact
We anticipate findings from this study will help evaluate the health impact of medications apart from relying on a randomized controlled trial. This genetic validation study will shed light in the identification of potential medications to be repurposed for treatment of diseases, and help screen potential medications for testing in subsequent RCTs.