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
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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 [Figure not available: see fulltext.]
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Diabetologia |
| Vol/bind | 64 |
| Udgave nummer | 1 |
| Sider (fra-til) | 42-55 |
| Antal sider | 14 |
| ISSN | 0012-186X |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
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. The funders had no role in study design, data collection, data analysis, interpretation or writing of the report. Acknowledgements Authors’ relationships and activities
Funding Information:
We are grateful to the study participants for their cooperation and willingness to participate. The laboratory technicians H. Vishof, L. S. Koch, S. Sidenius and C. S. Nielsen at Steno Diabetes Center Copenhagen (SDCC) are thanked for their great dedication, skilled assistance and coordination. C. S. Hansen, N. Safai, N. J. Johansen, J. I. B. Egholk (SDCC) are thanked for their assistance during the study. This work was supported by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation and University of Copenhagen. Parts of this study were presented in abstract form at the 79th Scientific Sessions of the ADA, San Francisco, CA, 7–11 June 2019 and at the 55th Annual Meeting of the EASD, Barcelona, 16–20 September 2019.
Funding Information:
We are grateful to the study participants for their cooperation and willingness to participate. The laboratory technicians H. Vishof, L. S. Koch, S. Sidenius and C. S. Nielsen at Steno Diabetes Center Copenhagen (SDCC) are thanked for their great dedication, skilled assistance and coordination. C. S. Hansen, N. Safai, N. J. Johansen, J. I. B. Egholk (SDCC) are thanked for their assistance during the study. This work was supported by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation and University of Copenhagen. Parts of this study were presented in abstract form at the 79th Scientific Sessions of the ADA, San Francisco, CA, 7?11 June 2019 and at the 55th Annual Meeting of the EASD, Barcelona, 16?20 September 2019. All authors have completed the ICMJE uniform disclosure form (available on request from the corresponding author) and declare that KF, HA, LB, DV, FP, KKBC, MBB, CTRV, MT, TFD and MEJ are employed by Steno Diabetes Center Copenhagen, a research hospital working in the Danish National Health Service. Until 31 December 2016 Steno Diabetes Center was owned by Novo Nordisk A/S and received part of its core funding from unrestricted grants from the Novo Nordisk Foundation and Novo Nordisk A/S. KF, DV and MEJ own shares in Novo Nordisk A/S. KF has received research support from AstraZeneca. TFD has consulted for Novo Nordisk, AstraZeneca and Boehringer Ingelheim and has received research support from Novo Nordisk and AstraZeneca. MR-L has received personal lecture fees from Novo Nordisk A/S. FP reports having received research grants from AstraZeneca, Novo Nordisk and Novartis and lecture fees from MSD, AstraZeneca, Novo Nordisk, Novartis, Eli Lilly and Boehringer Ingelheim and has served as a consultant for AstraZeneca, Novo Nordisk, Amgen and MSD. MEJ has received research grants from Amgen, Sanofi Aventis, Boehringer Ingelheim and Astra Zeneca.
Funding Information:
All authors have completed the ICMJE uniform disclosure form (available on request from the corresponding author) and declare that KF, HA, LB, DV, FP, KKBC, MBB, CTRV, MT, TFD and MEJ are employed by Steno Diabetes Center Copenhagen, a research hospital working in the Danish National Health Service. Until 31 December 2016 Steno Diabetes Center was owned by Novo Nordisk A/S and received part of its core funding from unrestricted grants from the Novo Nordisk Foundation and Novo Nordisk A/S. KF, DV and MEJ own shares in Novo Nordisk A/S. KF has received research support from AstraZeneca. TFD has consulted for Novo Nordisk, AstraZeneca and Boehringer Ingelheim and has received research support from Novo Nordisk and AstraZeneca. MR-L has received personal lecture fees from Novo Nordisk A/S. FP reports having received research grants from AstraZeneca, Novo Nordisk and Novartis and lecture fees from MSD, AstraZeneca, Novo Nordisk, Novartis, Eli Lilly and Boehringer Ingelheim and has served as a consultant for AstraZeneca, Novo Nordisk, Amgen and MSD. MEJ has received research grants from Amgen, Sanofi Aventis, Boehringer Ingelheim and Astra Zeneca.
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