DiRECT at two years: did type 2 diabetes remission last?

Why this study matters

The first year of DiRECT showed that almost half of people with recent type 2 diabetes could reach remission through a structured weight-management program. The obvious next question is whether it lasts. This two-year report answers that. It matters because weight regain is common after any weight-loss effort, and remission only counts if it holds.

Who was in the study

The trial ran at family practices in Scotland and the Tyneside area of England. Participants were 20 to 65 years old, had type 2 diabetes for less than six years, had a BMI of 27 to 45, and were not using insulin. BMI is weight in kilograms divided by height in metres squared. The main analysis included 149 people in each group. This report covers 24 months.

What the researchers did

This was an open-label, cluster-randomized trial. Cluster-randomized means whole practices were assigned by chance to deliver either the program or usual care. Open-label means participants and their care teams knew which group they were in. The statisticians did not.

The program began with withdrawal of diabetes and blood pressure medicines under supervision. Participants then used a total diet replacement, a formula diet of 825 to 853 kcal per day, for 12 to 20 weeks. Ordinary food was reintroduced in steps over 2 to 8 weeks. Structured support then continued to help maintain weight loss. The comparison group received guideline-based usual care. No weight-loss medicine was part of either group.

The two main outcomes at 24 months were losing at least 15 kg, and diabetes remission, defined as an HbA1c below 6.5% (48 mmol/mol) after withdrawal of diabetes medicines. HbA1c is a blood test that reflects average blood sugar over about three months. Remission was assessed separately at 12 and 24 months.

What they found

At 24 months, 17 people in the program group (11%) and 3 in the usual-care group (2%) had lost at least 15 kg. The adjusted odds ratio was 7.49 (95% confidence interval 2.05 to 27.32). Remission was reached by 53 people in the program group (36%) and 5 in the usual-care group (3%) (R32-C93). The adjusted odds ratio was 25.82 (8.25 to 80.84). An odds ratio compares the odds of an outcome between groups. The confidence interval is the range within which the true value would likely fall.

The adjusted difference in weight change between the groups was -5.4 kg (95% confidence interval -6.9 to -4.0), with the minus sign meaning more weight lost with the program. The adjusted difference in HbA1c was -4.8 mmol/mol (-8.3 to -1.4), which is -0.44 percentage points (-0.76 to -0.13). This was despite far fewer people in the program group using diabetes medicines.

In an analysis done after the trial was planned, the researchers looked at everyone who had kept off at least 10 kg at two years. Of 45 such people among the 272 with data, 29 (64%) were in remission. In the program group, 36 of 149 (24%) had kept off at least 10 kg.

Side effects and people who stopped

Serious adverse events were similar to those reported at 12 months. In the second year there were fewer in the program group than in the usual-care group: 9 versus 22. The summary does not report how many people stopped taking part in each group.

What this study does not tell you

• Remission fell from 46% at one year to 36% at two years. Staying in remission depended on continued support and keeping weight off.
• The trial was open-label and practice-randomized, which can introduce differences between groups beyond the program itself.
• Only people with recent diabetes who were not on insulin took part. Results may not apply to longer-standing diabetes.
• The 10 kg analysis was not planned in advance, and people were not randomized by how much weight they kept off.
• Medicines were withdrawn under medical supervision as part of the program, not as a decision people made alone.
• Our summary is based on the abstract and extracted data, not the full paper.

What it means in Canada

DiRECT shows that remission can hold for a meaningful share of people two years into a structured program with ongoing support, but not for everyone who reached it at one year. The program used no weight-loss medicine. For information on medicines used alongside diabetes care in Canada, see semaglutide in Canada and tirzepatide in Canada. For coverage, see public drug coverage by province. To find structured programs, see compare services.

Related reading

Other studies in this library that bear on the same question.

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