Diabetes drugs that may soon be prescribed more widely in England could save thousands of lives each year, suggests a new study by researchers at UCL and the London School of Hygiene & Tropical Medicine (LSHTM).
Last August the UK diabetes guideline committee at the National Institute for Health and Care Excellence (NICE) proposed SGLT-2 inhibitors alongside another drug, metformin, as a first-line treatment for people with type 2 diabetes. The final guidance is expected to be released on 18 February.
SGLT-2 inhibitors, which lower blood sugar levels in the body, have been shown in clinical trials to have a protective effect on the kidneys and the heart, reducing the chance of premature deaths from cardiac events such as strokes and heart attacks. However, these clinical trials focused on carefully selected groups of people with type 2 diabetes who met strict criteria. This left a gap in knowledge about the effects of these drugs in broader, diverse populations typically living with the condition.
The new study, published in BMJ Open Diabetes Research & Care and funded by the National Institute for Health and Care Research (NIHR), looked at how effective an SGLT-2 inhibitor had been in reducing deaths among a much wider group of people with type 2 diabetes than was included in trials.
The researchers, who looked at data from 60,000 people in the UK, found that people with type 2 diabetes who were prescribed the medicine were 24% less likely to have a premature death over an average of three years than those given another blood sugar-lowering drug.
Put another way, a life was saved for every 47 people who were prescribed the SGLT-2 inhibitor over three years.
Given an estimated three million people receive treatment for type 2 diabetes in the UK, this suggests very broadly that about 20,000 deaths could be prevented each year.
Lead author Dr David Ryan, a medical doctor specialising in clinical pharmacology and PhD candidate based at the UCL Institute of Health Informatics, said: "Our study shows this drug works very well in a much wider range of people with type 2 diabetes than we previously had evidence for. Our findings support NICE’s draft guidance proposing its use as a first treatment for type 2 diabetes, in addition to metformin - which would be a major shift in diabetes care affecting millions. The typical person with type 2 diabetes may live longer with these tablets."
Senior author Dr Patrick Bidulka, from LSHTM, said: "This study is a good example of how patient data can help inform patient care. It shows how we can use electronic health records safely to complement evidence from randomised controlled trials to improve outcomes for patients."
SGLT-2 inhibitors work by blocking sodium-glucose co-transporter 2 (SGLT-2) proteins in the kidneys. This stops excess sugar being reabsorbed into the bloodstream. Instead, the glucose stays in the kidneys and passes out of the body in urine.
Currently, people with type 2 diabetes are offered medication if diet and lifestyle changes are not enough to bring down blood sugar levels on their own.
For the study, the research team looked at anonymised GP records for 60,000 people in the UK who were prescribed either empagliflozin (an SGLT-2 inhibitor) or an alternative blood sugar-lowering drug (a dipeptidyl peptidase-4 inhibitor), between 2014 and 2022.
The team used a "trial emulation" approach, which uses key principles of clinical trial design (such as carefully defining which patients to include and deciding in advance how to carry out the analysis) to avoid common biases that arise in the analysis of big data from GP records.
The researchers included a much broader range of patients in their study than the major clinical trial upon which their analysis was modelled (the EMPA-REG randomised controlled trial).
Only one in five of this "real-world" group of patients would have been eligible for the clinical trial, which, for instance, only included individuals with established coronary artery disease and whose blood sugar levels stayed within a healthy range.
Senior author Dr Anoop Shah, based at UCL Institute of Health Informatics, said: "Clinical trials often recruit highly selected populations so their findings do not always generalise to the typical person living with type 2 diabetes. Our real-world analysis fills an important evidence gap and supports broader use of SGLT-2 inhibitors in clinical practice."
At present, metformin alone is the standard first-line treatment for type 2 diabetes across the UK. SGLT-2 inhibitors are only recommended at this stage if there are additional risk factors such as established cardiovascular disease or chronic heart failure. This study was submitted to NICE as part of the consultation process around the updated guidelines.
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