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.


Background: In type 2 diabetes, long-acting GLP-1 receptor agonists lower fasting plasma glucose and improve glycaemic control via their insulinotropic and glucagonostatic effects. In type 1 diabetes, their efficacy as an add-on treatment to insulin therapy is modest. Short-acting GLP-1 receptor agonists also lower postprandial glucose excursions in type 2 diabetes by decelerating gastric emptying rate. We aimed to test the efficacy of a short-acting GLP-1 receptor agonist in type 1 diabetes.

Methods: In the single-centre, parallel-group, randomised, double-blind, placebo-controlled MAG1C trial, patients with type 1 diabetes on multiple daily injection therapy aged 18 years and older with HbA1c 59-88 mmol/mol (7·5-10·0%) and a BMI of more than 22·0 kg/m2 were randomly assigned (1:1) through a computer-generated randomisation list to preprandial subcutaneous injection of 10 μg exenatide (Byetta) or placebo three times daily for 26 weeks as an add-on treatment to usual insulin therapy. Clinically assessed insulin titration was done by study staff. Participants and investigators were masked to treatment allocation. The primary endpoint was between-group difference in HbA1c after 26 weeks. Data were analysed with a baseline-adjusted linear mixed model in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03017352, and is completed.

Findings: Between Jan 4, 2017, and Jan 16, 2019, 108 participants were randomly assigned, 54 to exenatide and 54 to placebo; 23 participants discontinued treatment (17 in the exenatide group and six in the placebo group). From a baseline-adjusted mean of 66·4 mmol/mol (95% CI 64·9-67·8 [8·2%, 8·1-8·4]), HbA1c changed by -3·2 mmol/mol (-5·0 to -1·4 [-0·3%, -0·5 to -0·1]) with exenatide and -2·1 mmol/mol (-3·7 to -0·6 [-0·2%, -0·3 to -0·1]) with placebo after 26 weeks (estimated treatment difference of -1·1 mmol/mol (-3·4 to 1·2 [-0·1%, -0·3 to 0·1]; p=0·36). Exenatide increased the number of self-reported gastrointestinal adverse events (primarily nausea [48 events among 37 patients with exenatide, nine with placebo among 9 patients]). Two serious adverse events occurred in the exenatide group, and six occurred in the placebo group (none were considered to be related to the study drug).

Interpretation: Short-acting exenatide does not seem to have a future as a standard add-on treatment to insulin therapy in type 1 diabetes.

Funding: AstraZeneca.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Body Mass Index
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology
  • Double-Blind Method
  • Exenatide / therapeutic use*
  • Female
  • Glucagon-Like Peptides
  • Glycated Hemoglobin A / drug effects*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Meals / physiology*
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptides
  • Exenatide

Associated data

  • ClinicalTrials.gov/NCT03017352