DiRECT results: putting type 2 diabetes into remission with a low calorie (total diet replacement) formula diet

Total dietary replacement (TDR) plans like the LighterLife Total very-low-calorie diet (VLCD) are proving to be a formidable weapon in the war against type 2 diabetes, with the latest research from Diabetes UK showing that a TDR similar to the LighterLife Total VLCD plan can put type 2 diabetes into remission. The DiRECT study, supported by Diabetes UK’s largest ever research grant of £2.5m, was published in December 2017.

The authors noted, “Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care.” 

Type 2 diabetes is a chronic disorder currently considered to require lifelong treatment. The Diabetes Remission Clinical Trial (DiRECT) aimed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes.

An open-label (not blinded), cluster-randomised trial was run to compare a weight-management programme (withdrawal of antidiabetic and antihypertensive drugs, total diet replacement [TDR] 825–853 kcal/day formula diet for 3–5 months, stepped 2-8 week food reintroduction, and structured support for long term weight-loss maintenance) with best-practice care by guidelines (control). The co-primary outcomes were weight loss of 15kg or more, and remission of diabetes – defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months.

Between July 25, 2014 and Aug 5, 2017, 306 individuals aged 20-65 were recruited. They had all been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27–45kg/m², and were not receiving insulin. 149 participants per group comprised the intention-to-treat population.

At 12 months, a weight loss of 15kg or more was recorded in 36 (24%) participants in the intervention group and in no participants in the control group. Diabetes remission was achieved in 68 (46%) participants in the intervention group and 6 (4%) participants in the control group.

The more weight that a participant lost, the greater the likelihood of remission:

• none of 76 participants who gained weight achieved remission
• 6 (7%) of 89 participants who maintained 0–5kg weight loss achieved remission
• 19 (34%) of 56 participants with 5–10kg loss achieved remission
• 16 (57%) of 28 participants with 10–15kg loss achieved remission
• 31 (86%) of 36 participants who lost 15kg or more achieved remission

Mean bodyweight fell by 10kg in the intervention group versus 1kg in the control group.

Quality of life, as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7·2 points in the intervention group, and decreased by 2·9 points  in the control group.

Nine serious adverse events were reported by 7 of 157 participants (4%) in the intervention group and 2 were reported by 2 (1%) participants in the control group. Two serious adverse events (biliary colic and abdominal pain), occurring in the same participant, were deemed potentially related to the intervention. However, no serious adverse events led to withdrawal from the study.

Lean, Michael EJ et al (2017) Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster randomised trial. The Lancet, 391(10120):541-551.