An intensive 16-week program with insulin/liraglutide combination delayed diabetes relapse but did not sustain remission after drugs were stopped.
6.3% remission at 1 yearOnly about 1 in 16 intervention patients maintained diabetes remission a year after stopping all medications
What the researchers found
During the 16-week intervention, participants achieved significantly lower HbA1c (40 vs 51 mmol/mol, p < 0.0001) and lost more weight (3.3% vs 1.9%, p = 0.02) compared to controls.
After stopping all glucose-lowering drugs, there was a 37% lower hazard of diabetes relapse in the intervention group (HR 0.63, 95% CI 0.45-0.88, p = 0.007). However, this benefit did not last. At 12 weeks post-intervention, remission rates were 17.7% vs 12.5% (not significant). At 52 weeks, they were 6.3% vs 3.8% (not significant).
The key takeaway: intensive metabolic intervention delayed relapse but could not sustain remission once drugs were stopped.
Why it matters
Type 2 diabetes remission is a hot topic. Some studies show intensive weight loss can put diabetes into remission. This trial tested whether adding a powerful GLP-1/insulin combination to lifestyle changes could boost remission rates. The disappointing result, where remission did not last, suggests that more than 16 weeks of intervention may be needed, or that the weight loss achieved (3.3%) was too modest.
The numbers in context
- 159 participants randomized (79 intervention, 80 control)
- Age: 57 ± 10 years
- Diabetes duration: 2.6 ± 1.5 years
- BMI: 33.5 ± 6.5 kg/m²
- Baseline HbA1c: 53 ± 7 mmol/mol
- Post-intervention HbA1c: 40 vs 51 mmol/mol (p < 0.0001)
- Weight loss: 3.3% vs 1.9% (p = 0.02)
- Hazard of relapse: HR 0.63 (95% CI 0.45-0.88, p = 0.007)
- 52-week remission: 6.3% vs 3.8% (not significant)
How the study worked
This was a multicenter, open-label randomized controlled trial. 159 insulin-naive participants within 5 years of type 2 diabetes diagnosis were randomized to a 16-week intensive intervention (dietary coaching, exercise coaching, diabetes management coaching, metformin, and fixed-ratio insulin degludec/liraglutide) or standard care. After the intervention period, all glucose-lowering drugs were stopped, and patients were followed for one year for diabetes relapse and sustained remission.
Who was studied
159 insulin-naive adults within 5 years of type 2 diabetes diagnosis, BMI ~33.5, randomized to intensive intervention or standard care
What this study cannot tell us
The trial was open-label, meaning both patients and doctors knew who received the intervention, which could bias results. The weight loss achieved (3.3%) was modest compared to trials that successfully achieved remission. The 16-week intervention period may have been too short. The sample size (159) limited power to detect small remission rate differences. The insulin degludec/liraglutide combination may have suppressed HbA1c pharmacologically without changing the underlying disease.
How to read the evidence
Rated strong: multicenter randomized controlled trial with clear endpoints and follow-up, even though the result was negative for sustained remission.
When this study was published
Published in 2024. Adds to the growing body of diabetes remission research, including the influential DiRECT trial.
The bigger picture
Diabetes remission studies show that intensive weight loss is key. This trial's modest 3.3% weight loss likely explains why remission was not sustained — other successful remission programs achieved 10–15% weight loss.
Questions still open
- Would more aggressive weight loss targets have changed the outcome?
- Is 16 weeks long enough for lasting metabolic change?
- Would newer drugs like tirzepatide perform better in this protocol?
Common questions
Can you put diabetes into remission with drugs?
How much weight loss is needed for diabetes remission?
Read the original research
Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.
Diabetes, obesity & metabolism, 26(12), 5600-5608
Citation
Punthakee, Zubin; Hall, Stephanie; McInnes, Natalia; Sherifali, Diana; Tsiplova, Kate; Kirabo, Faith R; Ransom, Thomas P P; Harris, Stewart B; Lochnan, Heather A; Sigal, Ronald J; Ghosh, Mahua; Spaic, Tamara; Gerstein, Hertzel C. (2024). Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.. Diabetes, obesity & metabolism, 26(12), 5600-5608. https://doi.org/10.1111/dom.15926