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Randomized Controlled Trial
. 2020 Apr 13;15(4):e0231196.
doi: 10.1371/journal.pone.0231196. eCollection 2020.

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data

Rafael Gabriel  1   2 , Nisa Boukichou Abdelkader  3   4 , Tania Acosta  3   5 , Aleksandra Gilis-Januszewska  6 , Ricardo Gómez-Huelgas  7 , Konstantinos Makrilakis  8 , Zdravko Kamenov  9 , Bernhard Paulweber  10 , Ilhan Satman  11 , Predrag Djordjevic  12 , Abdullah Alkandari  13 , Asimina Mitrakou  14 , Nebojsa Lalic  15 , Stephen Colagiuri  16 , Jaana Lindström  17 , Jesús Egido  18 , Andrea Natali  19 , J Carlos Pastor  20 , Yvonne Teuschl  21 , Marcus Lind  22 , Luis Silva  3 , Ruy López-Ridaura  23 , Jaakko Tuomilehto  1   2   17   24   25 ; e-PREDICE Consortium
Affiliations
Randomized Controlled Trial

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data

Rafael Gabriel et al. PLoS One. .

Abstract

Objectives: To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes.

Methods: Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial.

Participants: Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey.

Intervention: Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function.

Results: One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%.

Conclusions: ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes.

Registration: - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.

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Conflict of interest statement

the authors received funding from Merck Serono GmbH and Boehringer Ingelheim. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. ePREDICE CONSORT flow diagram baseline.
See this image and copyright information in PMC

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