Dapagliflozin and Calorie Restriction Combo Shows Higher Remission Rates for Type 2 Diabetes: Multicenter Trial
China: Combining dapagliflozin with calorie restriction resulted in a higher rate of type 2 diabetes (T2D) remission, along with significant improvements in body fat and metabolic risk factors, compared to calorie restriction alone. The findings were published online in the BMJ journal.
In practice, the authors emphasized that their findings support using dapagliflozin with regular calorie restriction as an effective and sustainable approach for achieving remission in patients with early-stage type 2 diabetes.
Type 2 diabetes, affecting 422 million adults globally, can be reversed through intensive weight management. In the DiRECT trial, 46% of participants achieved diabetes remission with a 10% weight reduction. While bariatric surgery offers 60-70% remission, its high cost and risks limit its widespread acceptance. Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is commonly used to manage blood sugar levels in patients with T2D.
Against the above background, Yuejun Liu, an attending physician from the Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China, and colleagues aimed to evaluate the impact of combining dapagliflozin with calorie restriction on the remission of type 2 diabetes.
For this purpose, the researchers conducted a multicenter, double-blind, randomized, placebo-controlled trial across 16 centers in mainland China, from June 12, 2020, to January 31, 2023. The study involved 328 patients with type 2 diabetes, aged 20 to 70 years, a body mass index over 25, and a diabetes duration of less than 6 years. Participants were assigned either a calorie restriction regimen combined with dapagliflozin 10 mg/day or a placebo.
The primary outcome was the incidence of diabetes remission, defined as a glycated hemoglobin level of less than 6.5% and fasting plasma glucose under 126 mg/dL, with no use of antidiabetic drugs for at least two months. Secondary outcomes included changes in body weight, waist circumference, body fat, blood pressure, glucose homeostasis parameters, and serum lipid levels over 12 months.
The study revealed the following findings:
- Diabetes remission was achieved in 44% of patients in the dapagliflozin group compared to 28% in the placebo group, with a risk ratio of 1.56 over 12 months, meeting the predefined primary endpoint.
- Changes in body weight (difference −1.3 kg) and homeostasis model assessment of insulin resistance (difference −0.8) were significantly greater in the dapagliflozin group.
- Body fat, systolic blood pressure, and metabolic risk factors were significantly improved in the dapagliflozin group compared to the placebo group.
- There were no significant differences between the two groups in the occurrence of adverse events.
"Our multicenter, double-blind, randomized trial demonstrated that the combination of dapagliflozin and regular calorie restriction effectively achieved diabetes remission, reduced body weight, and improved metabolic risk factors in overweight or obese patients with type 2 diabetes. These results offer a practical alternative to intensive weight management for achieving remission in patients with early-stage type 2 diabetes," the researchers concluded.
Reference: BMJ 2025;388:e081820
