The Pages section of Primary Care Notebook comprises more than 30,000 concise, interlinked clinical reference articles, each focused on a specific primary care topic.
This month, I consider the use of use of a very low calorie diet in attaining remission of type 2 diabetes (T2D). Specifically, what do the results of DiRECT (Diabetes Remission Clinical Trial) tell us at year 5?
DiRECT had a very “brave” design: the trial enrolled patients 20–65 years of age who were within 6 years of their diagnosis of T2D and were not receiving insulin
In the treatment group, patients stopped their antidiabetes and antihypertensive medications and received total dietary replacement (basically, shakes with about 850 kcal per day) for 3–5 months, followed by a gradual reintroduction of food over 2–8 weeks. There was continued support from dieticians in the trial team. Diabetes and blood pressure medications were reintroduced if required.
At 12 months, about 50% of those in the treatment group were in remission (having an HbA1c <48 mmol/mol after ≥2 months off all antidiabetes medication). The greatest predictor was weight loss: in the overall study population, around 90% of those who lost ≥15 kg of weight achieved remission.
At 24 months, 36% of those in the treatment arm remained in remission.
So, what were the results after 60 months (5 years)? Some patients were lost to follow-up, but of those patients in the treatment arm who continued the study with low-intensity dietary support and had data available, 13% were still in remission.
Some people might think this disappointing, but imagine if you could give a treatment for 3 months and 5 years later your T2D register was around 10% smaller than it is today. That is impressive.
Comparing DiRECT with trials of antidiabetes medications given on an ongoing basis is not comparing like with like: the intervention and structure of the trial are very different. Remarkably, DiRECT has shown such an effect with a short-term intervention.
Another notable aspect of the 5-year results is that significant adverse events were less than half as prevalent in the treatment group than the control group, mainly due to more cancers in the latter. This may reflect the importance of fat mass as a risk factor for cancer.
The problem that DiRECT highlights is: how do we support these patients to maintain remission? Do we give further diet-replacement interventions? Should we use medications such as glucagon-like peptide-1 receptor agonists, since weight loss seems to be the main determinant of achieving remission? Food for thought.
For more information, see this page on GPnotebook.
Other highlights in this month’s email include updates on eosinophilic oesophagitis, the association between dementia and herpes simplex virus (HSV), and the link between traumatic brain injury and brain cancer risk.
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