First time randomized trial shows remission of T2DM with dietary and lifestyle intervention
Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trialLiterature - Lean MEJ, Leslie WS, Barnes AC et al., - The Lancet, Available online 5 December 2017. https://doi.org/10.1016/S0140-6736(17)33102-1
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- Data for the first primary outcome of weight loss ≥15kg were available for 285 (96%) participants: n=137 intervention, n=148 control) and for the second primary outcome of remission of diabetes, defined as HbA1c <6·5% after at least 2 months off all antidiabetic medications, from baseline to month 12, were obtained for 290 (97%) persons (n=142 and n=148, respectively).
- At 12 months, weight loss of at least 15 kg was seen in 26 (24%) of participants in the intervention group and in no control participants.
- Diabetes remission was seen in 68 (46%) of intervention participants and in six (4%) of control participants (OR: 19.7, 95%CI: 7.8-49.8, P<0.0001).
- The intervention group showed on average 10.0 kg weight loss and the control group 1.0 kg (adj difference: -8.8, 95%CI: -10.3 to -7.3, P<0.0001). BMI and weight change as a percentage of baseline weight showed similar patterns.
- In participants following the intervention, weight fell sharply during the total diet replacement phase, by 14.5 kg on average (95%CI: 13.4-15.5) followed by a small increase during the food introduction phase (1.0 kg, 95%CI: 0.3-1.6) and the weight loss management phase (1.9 kg, 95%CI: 1.2-2.5).
- Mean HbA1c reduced by -0.9% (SD: 1.4) in the intervention group, and increased with 0.1% (SD: 1.1) in the control group (adj difference: -0.85%, 95%CI: -1.10 to -0.59, P<0.0001).
- At 12 months, 74% of 148 participants in the intervention group were taking no antidiabetic medication, compared with 18% of 148 controls, and in the latter group eight patients commenced antidiabetic medication.
- Quality of life improved by 7.2 points (SD: 21.3) on the EQ-5D visual analogue scale in the intervention group, while it decreased by 2.9 points (SD: 15.5) in the control group.
- While antihypertensive drugs had been withdrawn in the 38 (48%) intervention participants who took them at baseline, mean BP at 12 months was similar between groups. At 12 months, antihypertensive drugs were prescribed to 32% of participants in the intervention group and in 61% of the control group.
- Nine serious adverse events (7 in intervention, 2 in control group) were reported during the 12 months of follow-up. Two serious events (reported in the same individual), biliary colic and abdominal pain, were deemed potentially related to the intervention.
These results show that T2DM of up to 6 years’ duration can be reversed by weight loss with help of an evidence-based structured weight management program delivered in a community setting, by routine primary care staff. Almost a quarter of participants who followed the intervention achieved at least 15 kg of weight loss at 12 months, and half maintained at least 10 kg reduction. Almost half of patients in the intervention group showed remission of diabetes, and were off antidiabetic medication. Remission was closely related to the degree of weight loss maintained at 12 months. This cohort will be followed up for at least 4 years.
To date, no findings from large-scale randomized trials were available on the effects of non-pharmacological treatment on remission of T2DM in patients receiving antidiabetic medication. Uusitupa  concludes that the obtained results are impressive and provide strong support for the view that T2DM is tightly associated with excessive fat mass in the body. These results, along with some other studies on T2DM prevention and some smaller intervention studies indicated that weight loss should be the primary goal in the treatment of T2DM, since it “results in improved insulin sensitivity in muscles and liver, decreases intra-organ fat content, and it might improve insulin secretion. In the long-term, weight loss might help to preserve β-cell mass. Once of the putative mechanisms could be decreased fat content of the pancreas, but more mechanistic studies are needed.” The role of physical activity and quality of diet, including dietary fibre and fatty acid composition are also important when considering the long-term success of prevention and treatment of T2DM.
The long-term results of the DiRECT study are important, because post-intervention weight regain is common among weight management studies in non-diabetic and diabetic populations. Uusitupa states “In view of the results of the DiRECT trial, a non-pharmacological approach should be revived. In clinical practice, anti- diabetic drugs seldom result in normalisation of glucose metabolism if patients’ lifestyles remain unchanged.”Uusitupa thinks that the time of diabetes diagnosis appears the best time point to start weight reduction and lifestyle changes, because the motivation of a patient is usually high.