Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases (MAG1C)

Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases: A Randomised, Placebo-controlled Trial

Patients with type 1 diabetes (T1D) depend on insulin therapy as substitution for the lack of endocrine insulin production due to an autoimmune destruction of beta-cells in the pancreatic inslets. Insulin therapy is based on long lasting basal insulin for controlling fasting plasma glucose, and short lasting mealtime insulin for the postprandial plasma glucose. The long term efficacy of this treatment is measured in glycated haemoglobin A1c (HbA1c) of <7.0% as the treatment goal.

Intensive insulin therapy is associated with side effects such as hypoglycaemia, weight gain, and unwanted exaggerated excursions in PPG. This may ultimately affect treatment compliance.

The abovementioned problems associated with insulin treatment in T1D can also be seen in insulin-treated patients with type 2 diabetes (T2D). However, in T2D the combination of insulin with glucagon-like peptide-1 (GLP-1) receptor agonist (RA) has proven effective in reducing the weight gain and insulin dose in insulin-treated patients with T2D without exacerbating the risk of hypoglycaemia.

Exenatid is a short lasting GLP-1RA approved for treatment in T2D, and the investigators intend to evaluate it in a randomized, controlled trial as add-on therapy to standard insulin therapy for patients with T1D.

The investigators hypothesise that the add-on of exenatide to insulin therapy in patients with T1D will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Placebos; Drug: Exenatide

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Gentofte, Capital Region, Denmark, 2820
      • Steno Diabetes Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• T1D according to WHO criteria with duration of ≥1 year
• Age ≥18 years
• BMI >22.0 kg/m2
• HbA1c >7.5% and <10.0% at visit 0 (screening)
• Able to count carbohydrates

Exclusion Criteria:

• Insulin pump treatment
• Hypoglycaemia unawareness (inability to register low blood glucose)
• Diabetic gastroparesis
• Compromised kidney function (eGFR <60 ml/min/1.73m2, dialysis or kidney transplantation)
• Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
• History of acute and/or chronic pancreatitis
• Subjects with personal or family history of medullary carcinoma or MEN syndrome
• Inflammatory bowel disease
• Cancer unless in complete remission for >5 years
• Proliferative retinopathy
• Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation
• Alcohol/drug abuse
• Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives
• Pregnant or nursing women
• Known or suspected hypersensitivity to trial product or related products
• Receipt of an investigational drug within 30 days prior to visit 0
• Simultaneous participation in any other clinical intervention trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Exenatide 10 mikrogram, thrice daily, subcutaneous injection prior to main meals, 6 months.	Drug: Exenatide; Other Names: Byetta
Placebo Comparator: Placebo; Placebo, thrice daily, subcutaneous injection prior to main meals, 6 months.	Drug: Placebos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Change in HbA1c from baseline to end of study (time 6 months)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events (including hypoglycaemic episodes)		6 months
changes in insulin dosage		6 months
changes in body weight		6 months
changes in BMI		6 months
changes in body composition	DXA scan measuring bonemineral density	6 months
changes in body composition	DXA scan measuring lean mass	6 months
changes in body composition	DXA scan measuring fat mass	6 months
changes in fasting plasma glucose		6 months
changes in post prandial plasma glucose		6 months
changes in fasting plasma levels of C-peptide		6 months
Quality of life self reported	Quality of Life Questionaire	6 months
Treatment satisfaction	Diabetes treatment satisfactory questionnaire status version	6 months
Treatment satisfaction	Diabetes treatment satisfactory questionnaire change version	6 months
dietary patterns	Food frequency questionaire three times during the intervention	6 months
HDL (High Density Lipoprotein)		6 months
LDL (Low Density Lipoprotein)		6 months
VLDL (Very Low Density Lipoprotein)		6 months
total cholesterol		6 months
triglycerides		6 months
proBNP (Pro-Brain Natriuretic Peptide)		6 months
hsCRP (High-Sensitivity C-Reactive Protein)		6 months

Collaborators and Investigators

• Sponsor: Filip Krag Knop
• Collaborators: Steno Diabetes Center Copenhagen

Publications and helpful links

General Publications

• Johansen NJ, Dejgaard TF, Lund A, Vilsboll T, Andersen HU, Knop FK. 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. BMJ Open. 2018 Jun 27;8(6):e021861. doi: 10.1136/bmjopen-2018-021861.
• Johansen NJ, Dejgaard TF, Lund A, Schluntz C, Frandsen CS, Forman JL, Wewer Albrechtsen NJ, Holst JJ, Pedersen-Bjergaard U, Madsbad S, Vilsboll T, Andersen HU, Knop FK. Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Apr;8(4):313-324. doi: 10.1016/S2213-8587(20)30030-9. Epub 2020 Mar 2.

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: January 2, 2017
• First Submitted That Met QC Criteria: January 9, 2017
• First Posted (Estimate): January 11, 2017

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; GLP-1; Incretins; Diabetes Mellitus, Type 1; Exenatide
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: Eudract-nr.: 2016-001365-92