Grant: Team Grant: UK-Canada Diabetes Research Team Grants

Diabetes is a chronic disease that affects how the body uses glucose which can lead to serious health problems including cardiovascular disease, neuropathy, nephropathy and eye disease. Type 2 diabetes is the most common type of diabetes, accounting for around 90% of all cases of diabetes. Treatment of type 2 diabetes typically proceeds with the drug metformin, followed by a range of new combination therapy options. The latest treatment guidelines offer treatment choices based upon risks, cost, and benefit, however there is considerable heterogeneity in who benefits and who is harmed from any of these treatments which are increasingly used in the UK and Canada. This UK-Canada collaboration brings together, for the first time, genetic data on randomised controlled trials of the newer diabetes medication, including SGLT2i trials (Dapagliflozin and Empagliflozin), GLP-1RA trials (Albiglutide, Lixisenatide), and DPP-4 inhibitor trials (Saxagliptin) in over 30,000 genetic samples. These unique resources are only available to the principal applicants and in combination provide great power to identify genetic variants that alter benefit to these medication, side effects and cardiovascular outcomes. Here, we will conduct a series of genetic studies making use of dense genomic data already available on all subjects which we will analyse using leading-edge bioinformatics and statistical approaches. We aim to identify genetic variants that alter response and outcomes of those new diabetes drugs (SGLT2i, GLP-1RA, DPP-4i) with the goal to enable the personalization of therapy for diabetes, such that we can one day prescribe the best anti-diabetes therapy suited to each individual patient. Thanks to the unique and extensive data collection from the joint UK-Canada teams and the outstanding combined expertise of the teams in precision medicine, diabetes, and cardiovascular disease, this study has the potential to provide a major advance in precision medicine of diabetes.