Diabetes remission study DiRECT reviewed with an update on global roll-out of remission programmes

Posted On: 9th November 2021

Mike Lean, Professor of Human Nutrition at the University of Glasgow reviewed the DiRECT trial of Total Diet Replacement (TDR) weight loss with behavioural and lifestyle guidance followed by weight maintenance to achieve diabetes remission in people with type 2 diabetes in TDMR Europe’s recent webinar. Prof Lean showed that the combination of significant weight loss using TDR followed by weight maintenance can achieve 10-15kg weight loss and diabetes remission in a proportion of participants.  Two-year follow up results were presented and information about the roll-out of remission programmes was given.

Professor Anthony Leeds, chair of TDMR Europe said ‘The team in Glasgow lead by Professor Lean in association with Professor Roy Taylor and colleagues at the University of Newcastle have marked the centenary of the discovery of insulin with landmark papers that may revolutionise the management of diabetes as much as did the first effective use of an insulin extract around one hundred years ago. Revolutions don’t happen quickly.  A huge number of first-rate clinical trials and investigations of mechanism has been undertaken over a number of years, along with health economic analyses of the cost benefits of this intervention. Translation into practice is underway in several countries.  Diabetes and its complications cause much human suffering and cost an appreciable proportion of national drug budgets, and are becoming increasingly prevalent, very rapidly. This may be slowed and the trend reversed over the coming five years or so by introducing effective weight loss and weight maintenance programmes.’

On 27th October, TDMR Europe’s online seminar brought together industry stakeholders, academics and others and showed the potential role of TDR in bringing down the incidence of obesity and severity of weight related comorbidities, such as type 2 diabetes, cardiovascular disease risk factors, osteoarthritis, and obstructive sleep apnoea. The recording of the webinar will be available soon on the TDMR Europe website.

More information on TDR is available here.

Professor Mike Lean is a principal investigator of the DiRECT study, chair of the department of human nutrition at the University of Glasgow, visiting professor at Otago University and visiting professor at the University of Sydney. He is a keen fiddle-player and climbs mountains.

FUNDING – The DiRECT trial was funded as a Strategic Research Initiative by Diabetes

1. The Cambridge Weight Plan donated all formula diet products.

 

Diabetes remission – update on global roll-out of remission programmes

Abstract

Many people can achieve “remission” from early type 2 diabetes (T2D) through weight loss from dietary changes. Remission (reducing blood sugar and HbA1c to non-diabetic levels without medication) improves wellbeing, reduces heart disease risks and reduces healthcare costs.

DiRECT, and DIADEM-1, both RCT trials, achieved mean weight losses >10kg at 12 months using established formula diets (low-calorie but nutrient-complete soups and shakes), and remissions for 46% or 61% of participants on an Intention to Treat (ITT) basis. Weight loss >10 kg led to remissions for 70-80%, which were well maintained at 2 years by keeping that weight off. Blood pressures fell, so about 30% were able to remain off medication. NAFLD, which often accompanies T2D, improved similarly.  A subset underwent mechanistic studies and MRI, which demonstrated high ectopic fat contents in liver and pancreas at baseline, which fell to normal (restoring normal pancreas morphology) with weight loss and remission.  Insulin production capacity was 50% at baseline, but rose to normal in those sustaining remissions.  Serious adverse events were fewer in the intervention group, and total medical care costs fell, so in a formal health economic analysis, the intervention helped people live longer, feel better and cost less.

Although proponents of low-carb and ketogenic diets are claiming that remission of T2D can be achieved, there is no RCT evidence, and the observational studies show remission rates on 12-20% on an ITT basis.

The DiRECT intervention (Counterweight-Plus) was delivered entirely in the community, and highly cost-effective (predicted cost-saving over >5 years).  However, weight loss maintenance is not easy and many need support to manage stress and cravings, emotional eating and handling relationships with others. Face-to-face support from healthcare professionals proved effective, but has high demands on staff and patients. The same diet intervention is now delivered remotely (via app or online, with video or telephone support) with similar weight loss results, but reduced demands on patients and staff time, and being cheaper can potentially reach more people.

Driven partly by the wishes of people currently living with T2D and partly by the cost-effectiveness analysis of DiRECT, interventions based on the ‘DiRECT Principles’ are now being provided within routine medical care.  In Scotland the evidence-based highly cost-effective Counterweight-Plus programme is provided in every NHS Scotland Health Board.  NHS England is instead offering a number of other interventions to an evaluated 5000 patients.  These programmes aimed at remission of T2D are also available, and popular, remotely-delivered to the public.

References:

1. Lean MEJ et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet 391, 541-551 (2018)
2. Lean MEJ et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. The Lancet Diabetes & Endocrinology, 7, 344-355 (2019)
3. Thom G et al. Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT). Diabetic Medicine, 38, 8, e14395 (2020)
4. Al-Mrabeh A et al. 2-year remission of type 2 diabetes and pancreas morphology: A post-hoc analysis of the DiRECT open-label, cluster-randomised trial. The Lancet Diabetes & Endocrinology 8 (12), 939-948 (2020)
5. Xin Y et al. Type 2 diabetes remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management. Diabetologia 63 (10), 2112-2122 (2020)
6. The DiRECT principles: giving Type 2 diabetes remission programmes the best chance of success. Hopkins MD, Taylor R, Lean MEJ,  Diabetic Medicine 36 (12), 1703-1704 (2019)
7. Churuangsuk C et al. Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission. Diabetologia, 2021