Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial

Nicklas Järvelä Johansen, Thomas Fremming Dejgaard, Asger Lund, Tina Vilsbøll, Henrik Ullits Andersen, Filip Krag Knop, Nicklas Järvelä Johansen, Thomas Fremming Dejgaard, Asger Lund, Tina Vilsbøll, Henrik Ullits Andersen, Filip Krag Knop

Abstract

Introduction: Persons with type 1 diabetes require intensive insulin therapy to achieve glycaemic control, but side effects, including hypoglycaemia and weight gain, may reduce treatment compliance. We hypothesise that add-on treatment of the short-acting glucagon-like peptide-1 receptor agonist, exenatide, to insulin therapy in persons with type 1 diabetes will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia. The present article describes a protocol developed to test this hypothesis.

Methods and analysis: One-hundred adult persons with type 1 diabetes for more than 1 year, insufficient glycaemic control (glycated haemoglobin A1c (HbA1c) between 58 and 86 mmol/mol) and body mass index >22.0 kg/m2 will be randomised to either exenatide 10 µg three times per day (at meal times) or placebo as add-on therapy to regular basal-bolus insulin treatment for 26 weeks. Primary endpoint is change in HbA1c between the two groups at end of treatment. Secondary endpoints include change in glycaemic excursions (assessed by continuous glucose monitoring); insulin dose; hypoglycaemic and adverse events; body weight, lean body and fat mass; dietary patterns; quality of life and treatment satisfaction; cardiovascular-disease risk profile; metabolomics; and arginine-tested plasma glucose, glucagon and C-peptide levels.

Ethics and dissemination: The study is approved by the Danish Medicines Agency, the Regional Scientific Ethics Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Positive, negative as well as inconclusive results will be sought disseminated at scientific meetings and in international peer-reviewed scientific journals.

Trial registration number: NCT03017352.

Keywords: clinical trials; general diabetes.

Conflict of interest statement

Competing interests: NJJ and TV have no competing interests. TFD has received research support from Novo Nordisk and AstraZeneca, and has received lecture fees from Novo Nordisk. AL has received lecture fees from Novo Nordisk, Boehringer Ingelheim and Eli Lilly. HUA owns stocks in Novo Nordisk and serves in advisory boards for Novo Nordisk and Astra Zeneca. FKK has served on scientific advisory panels and/or speaker’s bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gubra, MSD/Merck, Novo Nordisk, Sanofi and Zealand Pharma.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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