Innovative Tool may Predict Best Glucose-Lowering Drugs for Type 2 Diabetes: Lancet

Researchers at the University of Exeter have developed a tool to identify the most effective glucose-lowering drugs for individuals with type 2 diabetes. By predicting which medication will provide the greatest reduction in blood sugar levels, this user-friendly tool has the potential to improve health outcomes for millions.

Researchers at the University of Exeter, funded by the Medical Research Council, Wellcome and NIHR Exeter Biomedical Research Centre, and supported by Diabetes UK, have developed an innovative way of identifying the most effective glucose-lowering drugs for a person with type 2 diabetes. By predicting which drug will lead to the largest reduction in blood glucose levels, the easy-to-use tool could pave the way for better health for millions, at the push of a button.

Careful management of blood glucose levels is essential for reducing the risk of serious diabetes complications. However, keeping blood glucose levels in a safe range can be challenging, with only about a third of people with type 2 diabetes meeting targets2. With diabetes-related complications devastating lives and costing the UK healthcare system £6.2 billion every year3, there is an urgent need for new approaches to improve blood glucose management.

In England alone, more than three million people with type 2 diabetes use glucose-lowering drugs to manage their condition4. While metformin is the most common first treatment, five other major types of glucose-lowering drugs are available. However, their effectiveness varies widely from person to person and it has not been possible to determine the best glucose-lowering treatment for each patient – until now.

The new tool was created to tackle the challenge of which drug to choose after metformin. It was developed and tested using data from one million people with type 2 diabetes in the UK, linking GP and hospital records, with its accuracy verified with data from clinical trials.

The research revealed that only 18% of people with type 2 diabetes in the UK have been treated with the most effective glucose-lowering drug for them.

Modelling showed that starting people on the drug recommended by the new tool could lead to marked reductions in blood glucose levels (HbA1c) at one year, of around 5mmol/mol on average. Importantly, these improvements in blood glucose levels could approximately double the time until people need to start taking further diabetes medications. The tool’s use was also predicted to lower risks of developing serious long-term diabetes complications including heart attacks, strokes and kidney disease.

Using routinely collected clinical information, the tool offers a low-cost, practical, immediately usable solution that could transform the treatment of type 2 diabetes. For millions of people with type 2 diabetes, its use would ensure they receive the best treatment to help keep their blood sugars in target range and minimise their risk of developing life-limiting complications.

Dave Pomfrey, 67, from Hampshire, was diagnosed with type 2 diabetes 27 years ago. Dave was told he would need medication to manage his blood glucose levels and help reduce the risk of complications.

“The prospect of taking medication, potentially for life, along with the threat of complications was worrying. But having seen the impact of health complications faced by my relatives, who also had type 2 diabetes, I was willing to try anything.

“Over the years, I have experienced many changes to my medication to keep my blood glucose levels within range. Getting the most appropriate treatment as early as possible and reducing the back and forth of trying different medications could have such an impact on a person’s wellbeing.”

The tool’s performance in clinical practice is currently being assessed in 22,500 patients with type 2 diabetes across Scotland, which will inform its roll-out across the UK and globally, enabling a new era of personalised treatment for people with type 2 diabetes.

John Dennis, Associate Professor at the University of Exeter who led the study, said: “We have developed a completely new personalised approach for diabetes treatment, that could benefit everyone with type 2 diabetes in the UK and worldwide. For the first time, our model allows people living with type 2 diabetes to quickly identify the best treatment to manage their blood sugar levels, helping reduce their risk of diabetes complications. This offers a major advance on the current approach to choosing diabetes medications.”

Professor Andrew Hattersley from the University of Exeter, added: “Critically, our model can be implemented in clinical care immediately and at no additional cost. This is because it uses simple measures such as sex, weight and standard blood tests that are performed routinely. We hope that we can roll out the model quickly to make it available to help people with type 2 diabetes in the UK and across the world.”

Dr Elizabeth Robertson, Director of Research and Clinical at Diabetes UK, said: “This innovation using routine clinical data could help countless people with type 2 diabetes to get their blood sugars levels into a safe range, significantly reducing their risk of devastating diabetes complications and easing the burden of living with this relentless condition. If shown to be effective in practice and widely adopted by health services in the UK and globally, this tool could mark the most significant advance in type 2 diabetes care in more than a decade, improving health outcomes for millions.”

Dr Adam Babbs, Head of Translation at the Medical Research Council, which was a funder of the study, said: “This study is a trailblazing example of why we’re backing research into the next frontier in medicine: the development of precision medicine, which ensures that the right patient receives the right therapy at the right time. With large variation between individuals with type 2 diabetes in how they respond to treatments, and many different treatments available, precision medicine like this has huge potential to improve patient outcomes and provide efficiencies for the healthcare system.”

References: John M Dennis, PhDa j.dennis@exeter.ac.uk ∙ Katherine G Young, PhDa ∙ Pedro Cardoso, PhDa ∙ Laura M Güdemann, PhDa ∙ Andrew P McGovern, MDa ∙ Prof Andrew Farmer, DMb ∙ Prof Rury R Holman, FMedScic,d ∙ Prof Naveed Sattar, MDe ∙ Trevelyan J McKinley, PhDa ∙ Prof Ewan R Pearson, PhDf ∙ Prof Angus G Jones, PhDa ∙ Beverley M Shields, PhDa ∙ Prof Andrew T Hattersley, DMa on behalf of the MASTERMIND Consortium† DOI 10.1016/S0140-6736(24)02617-5