Steno Diabetes Center Copenhagen, Gentofte, Denmark.
University of Southern Denmark, Copenhagen, Denmark.
Diabetologia. 2021 Jan;64(1):42-55. doi: 10.1007/s00125-020-05306-1. Epub 2020 Oct 16.
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.
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, 30-70 years of age, and prediabetes (HbA 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%).
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.
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.
目的/假设：我们旨在研究三种降糖干预措施在超重或肥胖且 HbA 定义的糖尿病前期患者中的短期疗效和安全性。
PRE-D 试验是在丹麦 Gentofte 的 Steno Diabetes Center Copenhagen 进行的一项随机、对照、平行、多臂、开放标签、非盲试验。120 名 BMI≥25kg/m、年龄 30-70 岁且患有糖尿病前期（HbA 39-47mmol/mol [5.7-6.4%]）的参与者按 1:1:1:1 的比例随机分为达格列净（10mg 每日一次）、二甲双胍（1700mg 每日）、基于间隔的运动（每周 5 天，每次 30 分钟）或对照组（习惯性生活方式）。参与者在基线和随机分组后 6、13 和 26 周接受检查。主要结局是使用连续血糖监测系统（预先指定的 MAGE 最小临床重要差异约为 30%）确定的血糖变异性（计算为平均血糖波动幅度 [MAGE]）在 13 周时的变化。
112 名参与者在 13 周时接受了检查，111 名参与者在 26 周时接受了随访。与对照组相比，达格列净组 MAGE 略有下降（17.1% [95%CI 0.7, 30.8]，p=0.042），运动组略有非显著下降（15.3% [95%CI -1.2, 29.1]，p=0.067），而二甲双胍组 MAGE 无变化（0.1% [95%CI -16.1, 19.4]，p=0.991））。与二甲双胍组相比，达格列净组 MAGE 在 13 周时降低了 17.2%（95%CI 0.8, 30.9；p=0.041），运动组降低了 15.4%（95%CI -1.1, 29.1；p=0.065），而运动组和达格列净组之间无差异（2.2% [95%CI -14.8, 22.5]，p=0.815）。对照组发生 1 例严重不良事件（肺癌）。
结论/解释：与对照组和二甲双胍治疗相比，达格列净和基于间隔的运动治疗导致血糖变异性相似但略有改善。这些发现对糖尿病前期的临床重要性尚不确定。
ClinicalTrials.gov NCT02695810 资金：该研究由 Novo Nordisk 基金会、阿斯利康 AB、丹麦创新基金会、哥本哈根大学和 Ascensia Diabetes Care Denmark ApS 资助
