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Randomized Controlled Trial
. 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  1 , Martin B Blond  2 , Lea Bruhn  2 , Hanan Amadid  2 , Dorte Vistisen  2 , Kim K B Clemmensen  2 , Camilla T R Vainø  2 , Camilla Pedersen  2 , Maria Tvermosegaard  2   3 , Thomas F Dejgaard  2 , Kristian Karstoft  4 , Mathias Ried-Larsen  4   5 , Frederik Persson  2 , Marit E Jørgensen  2   3
Affiliations
Randomized Controlled Trial

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 et al. Diabetologia. 2021 Jan.

Abstract

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 HbA1c.

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/m2, 30-70 years of age, and prediabetes (HbA1c 39-47 mmol/mol [5.7-6.4%]) were randomised 1:1:1:1 to dapagliflozin (10 mg once daily), metformin (1700 mg daily), interval-based exercise (5 days/week, 30 min/session) or control (habitual lifestyle). Participants were examined at baseline and at 6, 13 and 26 weeks after randomisation. The primary outcome was the 13 week change in glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) determined using a continuous glucose monitoring system (pre-specified minimal clinically important difference in MAGE ∼30%).

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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References

    1. Eckel RH, Kahn SE, Ferrannini E et al (2011) Obesity and type 2 diabetes: what can be unified and what needs to be individualized? J Clin Endocrinol Metab 96(6):1654–1663. https://doi.org/10.1210/jc.2011-0585 - DOI - PubMed - PMC
    1. Færch K, Johansen NB, Vistisen D, Jørgensen ME (2014) Cardiovascular risk stratification and management in pre-diabetes. Curr Diab Rep 14:493 - DOI
    1. Knowler WC, Barrett-Connor E, Fowler SE et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346(6):393–403 - DOI
    1. Tuomilehto J, Lindström J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344(18):1343–1350 - DOI
    1. Pan XR, Li GW, Hu YH et al (1997) Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20(4):537–544 - DOI

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