Adding the SGLT2 inhibitor, dapagliflozin, to a restricted calorie diet achieves higher rates of remission of type 2 diabetes than calorie restriction alone in overweight or obese people, according to a study published in The BMJ.
The study found that a regimen of dapagliflozin plus moderate calorie restriction significantly increased the rate of remission of diabetes (44%) compared with calorie restriction alone (28%).
Subjects in the dapagliflozin group also lost more weight, and showed greater improvements in systolic blood pressure, body fat, high density lipoprotein cholesterol concentrations and serum triglycerides, than those in the control group.
Previous studies, including the DiRECT study, have shown that intensive weight management programmes can lead to remission of type 2 diabetes in almost half (46%) of patients with type 2 diabetes, but adhering to an approximately 800-850 kcal/day formula diet for up to the first 5 months of the programme can be difficult. In the Look AHEAD study, the calorie restriction was less extreme (1200-1800 kcal/day) but the rate of remission was only 11.5% in the first year.
In this study, the aim was to achieve an ‘energy deficit’ of 500-750 kcal/day, which was considered practicable. Adding dapagliflozin resulted in extra excretion of approximately 70-80 g of glucose in the urine, and additional 280-320 kcal energy loss per day. The combination was more effective than either calorie restriction or dapagliflozin alone, and produced a remission rate that was close to that achieved in the DiRECT study, the authors say.
Although the study population size was calculated to be sufficient to demonstrate statistical significance, it was relatively small – 328, randomly assigned to the active treatment and placebo groups, 165 and 163, respectively. And in this study, remission was defined as normal glycaemic levels for 2 months, not 3 as some experts now claim is more conclusive.
Liu Y, et al. Dapagliflozin plus calorie restriction for remission of type 2 diabetes: multicentre, double blind, randomised, placebo controlled trial. BMJ 2025;388:e081820
