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Diabetologia. 2021 Jan;64(1):42-55. doi: 10.1007/s00125-020-05306-1. Epub 2020 Oct 16.

The effects of dapagliflozin, metformin or exercise on glycaemic variability in overweight or obese individuals with prediabetes (the PRE-D Trial): a multi-arm, randomised, controlled trial.


Kristine Færch, Martin B Blond, Lea Bruhn, Hanan Amadid, Dorte Vistisen, Kim K B Clemmensen, Camilla T R Vainø, Camilla Pedersen, Maria Tvermosegaard, Thomas F Dejgaard, Kristian Karstoft, Mathias Ried-Larsen, Frederik Persson, Marit E Jørgensen


  1. Steno Diabetes Center Copenhagen, Gentofte, Denmark. [email protected].
  2. Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  3. University of Southern Denmark, Copenhagen, Denmark.
  4. The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  5. The Danish Diabetes Academy, Odense, Denmark.

PMID: 33064182 DOI: 10.1007/s00125-020-05306-1


AIMS/HYPOTHESIS: We aimed to investigate the short-term efficacy and safety of three glucose-lowering interventions in overweight or obese individuals with prediabetes defined by HbA

METHODS: The PRE-D Trial was a randomised, controlled, parallel, multi-arm, open-label, non-blinded trial performed at Steno Diabetes Center Copenhagen, Gentofte, Denmark. One hundred and twenty participants with BMI ≥25 kg/m

RESULTS: One hundred and twelve participants attended the examination at 13 weeks and 111 attended the follow-up visit at 26 weeks. Compared with the control group, there was a small decrease in MAGE in the dapagliflozin group (17.1% [95% CI 0.7, 30.8], p = 0.042) and a small, non-significant, reduction in the exercise group (15.3% [95% CI -1.2, 29.1], p = 0.067), whereas MAGE was unchanged in the metformin group (0.1% [95% CI -16.1, 19.4], p = 0.991)). Compared with the metformin group, MAGE was 17.2% (95% CI 0.8, 30.9; p = 0.041) lower in the dapagliflozin group and 15.4% (95% CI -1.1, 29.1; p = 0.065) lower in the exercise group after 13 weeks, with no difference between exercise and dapagliflozin (2.2% [95% CI -14.8, 22.5], p = 0.815). One serious adverse event occurred in the control group (lung cancer).

CONCLUSIONS/INTERPRETATION: Treatment with dapagliflozin and interval-based exercise lead to similar but small improvements in glycaemic variability compared with control and metformin therapy. The clinical importance of these findings in prediabetes is uncertain.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02695810 FUNDING: The study was funded by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation, the University of Copenhagen and Ascensia Diabetes Care Denmark ApS Graphical abstract.

Keywords: Dapagliflozin; Exercise; Glycaemic variability; Intermediate hyperglycaemia; Metformin; Overweight; Prediabetes; SGLT2 inhibitor


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