Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial
Natalia McInnes, Stephanie Hall, Heather A. Lochnan, Stewart B. Harris, Zubin Punthakee, Ronald J. Sigal, Irene Hramiak, Mohammed Azharuddin, Joanne F. Liutkus, Jean‐François Yale, Farah Sultan, Ada Smith, Rose E. Otto, Diana Sherifali, Yan Yun Liu, Hertzel C. Gerstein,- Endocrinology
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
Abstract
Aim
Non‐surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short‐term intensive glucose‐lowering therapy.
Methods
In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time‐to‐event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied.
Results
The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40‐0.81; p = .002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14‐3.24) and 1.83 (1.03‐3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00‐3.53) at 48 weeks and 2.05 (0.98‐4.29) at 64 weeks.
Conclusions
A 12‐week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes.