Landmark two-year diabetes DiRECT trial

New findings from an extension of the landmark DiRECT study, revealing it’s possible to maintain significant weight loss and keep type 2 diabetes in remission for at least 5 years. The findings will be presented at the Diabetes UK Professional Conference next week.

Weight loss can put type 2 diabetes into remission for at least five years, reveal latest findings from DiRECT (The Diabetes Remission Clinical Trial):

• Landmark two-year DiRECT trial was first to show that remission from type 2 diabetes is possible through diet-induced weight loss in a primary care setting
• New results from three-year extension of DiRECT trial reveal 23% of participants who were in remission after two years remained in remission at five years, maintaining an average weight loss of 8.9kg
• Overall, the low-intensity support offered in the DiRECT extension led to significant average weight loss maintenance of 6.1kg at five years, and sustained improvements to blood sugar levels and blood pressure

New findings from a three-year extension of the landmark Diabetes UK-funded Diabetes Remission Clinical Trial (DiRECT) have revealed that nearly a quarter (23%) of participants who were in remission from type 2 diabetes at two years in the original trial remained in remission at five years, no longer needing to use diabetes medications to manage their blood sugar levels. Those who were still in remission had an average weight loss of 8.9kg at five years.

The research revealed that the proportion of participants in remission after five years was more than three times that of the DiRECT control group, who did not take part in the original low-calorie diet programme or receive continued low-intensity weight management support in the extension trial.

The research, led by Professor Mike Lean, at the University of Glasgow, and Professor Roy Taylor, at Newcastle University, will be presented at the Diabetes UK Professional Conference 2023 in Liverpool on Wednesday 26 April.

The original DiRECT trial of a weight management programme for people with a diagnosis of type 2 diabetes within the last six years, involved a 12-week low-calorie formula diet, followed by support to gradually reintroduce healthy food and maintain weight loss. The landmark trial was the first to show that remission from type 2 diabetes is possible through a dietary intervention in primary care, with almost half (46%) of people in remission at one year, and 36% at two years.

In the extension study, to understand the longer-term benefits of the programme, 95 intervention group participants of the original two-year DiRECT study (48 of whom were in remission at the start of the extension) continued to receive support to help maintain weight loss over the next three years. They received nurse or dietitian appointments at their GP surgery every three months to review their weight, blood sugar levels and blood pressure, and were offered advice and support to maintain their weight loss.

Participants who regained over 2kg during years 3-5 were offered an additional package of support, available once each year, consisting of the low-calorie ‘soups and shakes’ diet for four weeks, followed by support while reintroducing normal meals.

During the three-year extension, 82 participants from the original DiRECT control group – who originally received best type 2 diabetes care according to guidelines – were advised to lose weight. Control participants did not receive the three-monthly appointments, or additional ‘soups and shakes’ packages during the extension period.

• Data, available from 85 participants of the original DiRECT intervention group, revealed an average five-year weight loss of 6.1kg.
  o Of the 48/85 participants who were in remission at the start of the extension period, 11 (23%) were still in remission at 5 years, with an average five-year weight loss of 8.9kg.
• Data, available from 82 participants of the original DiRECT control group, showed an average five-year weight loss of 4.6kg, with 3.4% in remission.
• Overall, the intervention group saw greater improvements in blood pressure and blood sugar levels, and fewer needed medication, compared to the control group.
• The number of ‘serious adverse events’ (events resulting in hospital admission) in the intervention group was less than half that in the control group. The findings also support growing evidence that weight loss, and remission from type 2 diabetes, can prevent or delay the complications of diabetes.

Kieran Ball, 47, from Morpeth was diagnosed with type 2 diabetes in 2013 and started the DiRECT trial the following year. Kieran put his type 2 diabetes into remission within one year, and having taken part in the DiRECT Extension study, his diabetes is still remission eight years later. Kieran said:

“DiRECT has 100% been life-changing. Those few months on the low-calorie diet were hard, but I’d do it again no question. DiRECT was an opportunity to reboot the way I was living, and I’m so grateful for what being healthy has given me the opportunity to do. It’s amazing that what I went through all those years ago is still benefiting me today. I’m still in remission and not on any diabetes medication – I can’t quite believe how long it’s been.”

Professor Mike Lean, at the University of Glasgow, said:

“Type 2 diabetes causes a range of progressive and life-shortening complications, notably blindness, infections, amputations, kidney failure and heart failure. It affects over four million people in UK and accounts for about 10% of NHS funding. The DiRECT Extension has shown us that a substantial proportion of people, managed in primary care, can maintain sufficient weight loss to be free from the condition for up to five years.

“The weight management intervention also reduced blood pressure and the need for antihypertensive drugs.

“The findings are important both for individuals and for national considerations of healthcare costs. The programme used in DiRECT is a huge improvement on previous management of type 2 diabetes, but future studies must seek even better ways to help maintain weight loss.”
Professor Roy Taylor at Newcastle University, said:

“The DiRECT five-year follow up shows that the rapid weight loss programme brings about considerable weight loss at five years with low-intensity support. The most important question now is how the follow-up programme can be even more successful at an affordable cost.”

Dr Elizabeth Robertson, Director of Research at Diabetes UK, said:

“Diabetes UK is proud to be at the forefront of over a decade of pioneering research into type 2 diabetes remission. Our DiRECT study has been pivotal in transforming the lives of people with type 2 diabetes by showing that the condition can be put into remission through weight loss. The new findings from DiRECT confirm that for some people, it is possible to stay in remission for at least five years.

“For those who put type 2 diabetes into remission, it can be life-changing, offering a better chance of a healthier future. For those that aren’t able to go into remission, losing weight can still lead to major health benefits, including improved blood sugar levels, and reduced risk of serious diabetes complications such as heart attack and stroke.

“DiRECT inspired the NHS low-calorie diet programme, granting many more people with type 2 diabetes the opportunity to put the condition into remission. We now need to understand how best to support more people to maintain weight loss and stay in remission in the long term.”

1. The Diabetes Remission Clinical Trial (DiRECT) was funded by Diabetes UK as a Strategic Research Initiative to Professors Lean and Taylor, with support in kind for formula diet from Cambridge Weight Plan. Details and lists of publications available on https://www.directclinicaltrial.org.uk
2. Participants were defined as in remission if they had long-term blood glucose levels (HbA1c) of less than 48mmol/mol (6.5%) without needing to use any Type 2 diabetes medications. This meets the 2021 international consensus agreement on the definition of remission. Reference: Diabetes Care 2021; doi:10.2337/dci21-0034N
3. New Guidelines for Diet in the Management of Diabetes, from the Diabetes Nutrition Study Group of the European Association for the Study of Diabetes, published 18th April 2023 in Diabetologia, stress the value of weight management and remission of type 2 diabetes.
4. The DiRECT and DiRECT Extension studies used the Counterweight-Plus weight management programme, initially delivered face-to-face in NHS primary care, but now adapted for remote/digital delivery. Other programmes which follow the ‘DiRECT Principles’ are likely to be similarly effective. DOI: 10.1111/dme.14126
https://www.directclinicaltrial.org.uk/Pubfiles/The%20DiRECT%20principles.pdf

Further details about results:

• 3.4% of original DiRECT control group who provided data were in remission at five years, compared to 12% of participants of the original intervention group.
• Clinical data, including health events and medications, were extracted from the routine NHS medical records of all participants. Serious adverse events were those which result in hospital admissions, or which have potentially fatal or incapacitating consequences.

About type 2 diabetes

Type 2 diabetes is a complex condition with many risk factors, including age, genetics, ethnicity and bodyweight. More than five million people in the UK are currently living with diabetes, around 90% of whom have type 2.

About type 2 remission

Type 2 diabetes remission means that a person no longer has high blood glucose levels, and does not need to take diabetes medications.
A person with type 2 diabetes is in remission if:
a. They have had an HbA1c level below 6.5% (48mmol/mol) for a least three months
AND
b. They have not taken any medications to manage their blood glucose levels during this time.
Diabetes UK recommends that people who are in remission still get their annual health check-ups, to check that their blood sugar levels haven’t returned into the diabetes range, particularly if they have regained weight, and they haven’t developed any complications. Weight loss surgery has been shown to put type 2 diabetes into remission in 30 to 60 percent of cases, but access is a challenge.
About Diabetes UK

Diabetes UK’s aim is creating a world where diabetes can do no harm. Diabetes is the most devastating and fastest growing health crisis of our time, affecting more people than any other serious health condition in the UK – more than dementia and cancer combined. There is currently no known cure for any type of diabetes. With the right treatment, knowledge and support, people living with diabetes can lead a long, full and healthy life. For more information about diabetes and the charity’s work, visit www.diabetes.org.uk