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 1c . 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 2 , 30-70 years of age, and prediabetes (HbA 1c 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.
IntroductionThe primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A1c (HbA1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors.Methods and analysisThe Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA1c-defined prediabetes to be addressed.Trial registrationNCT02695810
BackgroundAmbiguity exists in relation to the role of physical activity (PA) for cardiovascular disease (CVD) risk reduction. We examined the interplay between PA dimensions and more conventional CVD risk factors to assess which PA dimensions were associated with the first CVD event and whether subgroup differences exist.MethodsA total of 1449 individuals [median age 65.8 (IQR: 61.2, 70.7) years] with low to high risk of type 2 diabetes and free from CVD from the Danish ADDITION-PRO study were included for survival analysis. PA was measured by individually calibrated heart rate and movement sensing for 7 consecutive days. The associations of different PA dimensions (PA energy expenditure, time spent in light-, moderate- and vigorous intensity PA), sedentary time and other conventional CVD risk factors with the first CVD event were examined by tree-structured survival analysis. Baseline information was linked to data on the first CVD event (ischemic heart disease, ischemic stroke, heart failure, atrial flutter/fibrillation and atherosclerotic disease) and mortality obtained from Danish registers.ResultsDuring a median follow-up time of 5.5 (IQR: 5.1–6.1) years, a total of 201 individuals (13.9%) developed CVD. Overall CVD incidence rate was 2.6/100 person-years. PA energy expenditure above 43 kJ/kg/day was associated with lower rates of CVD events among participants ≤ 70 years and with HbA1c ≤ 5.7% (39 mmol/mol), systolic blood pressure ≤ 156 mmHg and albumin creatinine ratio ≤ 70 (incidence rates 0.0–0.8/100 person-years).ConclusionsAny type of PA resulting in increased PA energy expenditure may over time be the best prevention strategy to uphold reduced risk of CVD.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0769-x) contains supplementary material, which is available to authorized users.
Aim: To explore how participating in a randomised controlled trial affected motivation, barriers and strategies in the process of health behaviour change among individuals with prediabetes.Methods: An extension to the PRE-D trial, a qualitative study investigated the efficacy of glucose-lowering interventions (metformin, dapagliflozin or exercise) compared with a control group among individuals with prediabetes and overweight/obesity. Data were collected through separate focus group interviews with participants using semi-structured interview guides inspired by health behaviour change theories. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis with an inductive-deductive approach.Results: Four interrelated themes were generated from interviews: (1) 'selfconstruction of prediabetes', on how participants understood the term 'prediabetes', (2) 'altered health image', on how participants' health perceptions were affected, (3) 'personal strategies for health behaviour change', on different ways to attempt to implement behaviour changes and (4) 'the process of health behaviour change', on how participants progressed and relapsed while trying to change behaviour. Themes relate to the health belief model, self-determination theory, self-efficacy and the trans-theoretical model of change. Participants shared their experiences and thoughts during interviews and inspired each other, which led some participants to develop a new perspective on prediabetes severity and increased their motivation for behaviour change. Conclusions: How participants perceived and accepted, rejected or neglected prediabetes appeared to affect their health images and whether they realised a need for behaviour change. Their achievements during interventions, health literacy, self-efficacy and perceived support from their social networks, professionals and technological aids influenced the maintenance of health behaviour changes.
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