Dapagliflozin plus calorie restriction for remission of type 2 diabetes: multicentre, double blind, randomised, placebo controlled trial

BMJ. 2025 Jan 22:388:e081820. doi: 10.1136/bmj-2024-081820.

Abstract

Objective: To assess the effect of dapagliflozin plus calorie restriction on remission of type 2 diabetes.

Design: Multicentre, double blind, randomised, placebo controlled trial.

Setting: 16 centres in mainland China from 12 June 2020 to 31 January 2023.

Participants: 328 patients with type 2 diabetes aged 20-70 years, with body mass index >25 and diabetes duration of <6 years.

Interventions: Calorie restriction with dapagliflozin 10 mg/day or placebo.

Main outcome measures: Primary outcome: incidence of diabetes remission (defined as glycated haemoglobin <6.5% and fasting plasma glucose <126 mg/dL in the absence of all antidiabetic drugs for at least 2 months); secondary outcomes: changes in body weight, waist circumference, body fat, blood pressure, glucose homoeostasis parameters, and serum lipids over 12 months.

Results: Remission of diabetes was achieved in 44% (73/165) of patients in the dapagliflozin group and 28% (46/163) of patients in the placebo group (risk ratio 1.56, 95% confidence interval (CI) 1.17 to 2.09; P=0.002) over 12 months, meeting the predefined primary endpoint. Changes in body weight (difference -1.3 (95% CI -1.9 to -0.7) kg) and homoeostasis model assessment of insulin resistance (difference -0.8, -1.1 to -0.4) were significantly greater in the dapagliflozin group than in the placebo group. Likewise, body fat, systolic blood pressure, and metabolic risk factors were significantly more improved in the dapagliflozin group than in the placebo group. In addition, no significant differences were seen between the two groups in the occurrence of adverse events.

Conclusion: The regimen of dapagliflozin plus regular calorie restriction achieved a much higher rate of remission of diabetes compared with calorie restriction alone in overweight or obese patients with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT04004793.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds* / therapeutic use
  • Blood Glucose / metabolism
  • Caloric Restriction* / methods
  • China / epidemiology
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2* / diet therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Female
  • Glucosides* / therapeutic use
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Remission Induction
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • dapagliflozin
  • Glucosides
  • Benzhydryl Compounds
  • Blood Glucose
  • Glycated Hemoglobin
  • Sodium-Glucose Transporter 2 Inhibitors
  • Hypoglycemic Agents

Associated data

  • ClinicalTrials.gov/NCT04004793