Clinical Trial Tests Efficacy of Short-Acting GLP-1 Receptor Agonist in Type 1 Diabetes

April 2, 2020

A clinical trial funded by AstraZeneca evaluated the use of short-acting GLP-1 receptor agonists as an add-on treatment to insulin therapy in type 1 diabetes.

Long-acting glucagon-like peptide-1 (GLP-1) receptor agonists are currently used to lower fasting plasma glucose and improve glycemic control through insulinotropic and glucagonostatic effects in patients with type 2 diabetes. GLP-1 receptor agonists also lower postprandial glucose excursions by decelerating gastric emptying rate.

A study published in The Lancet Diabetes & Endocrinology evaluated the efficacy of short-acting GLP-1 receptor agonists in patients with type 1 diabetes.

The MAG1C (Meal-time Administration of Exenatide for Glycemic Control in Type 1 Diabetes Cases) trial involved a single-center, parallel-group; the trial was randomized, double-blind, and placebo-controlled.

Efficacy evaluation methods included multiple day injection therapy of adults 18 years or older with HbA1c 59-88 mmol/mol (7.5-10.0%) and a body mass index of more than 22.0kg/m2. Participants were randomly assigned either preprandial subcutaneous injection of 10 μg exenatide (Byetta) or placebo through a computer-generated randomization list. Patients took their assigned dosage three times daily for 26 weeks as an additional treatment to their usual insulin therapy.

MAG1C was primarily concerned with identifying between-group difference in HbA1c after the 26-week period. In total, 108 participants contributed to the study–54 to the exenatide group and 54 to placebo group.

Overall, 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), according to the study.

In the study exenatide use increased the number of self-reported gastrointestinal adverse effects (AEs), primarily nausea. There were 48 AEs among 37 patients treated with exenatide, and 9 events with placebo among 9 patients. Two serious AEs occurred in the exenatide group, and 6 in the placebo group; however, none were considered related to the drug under study.

“Short-acting exenatide does not seem to have a future as a standard add-on treatment to insulin therapy in type 1 diabetes,” the study authors wrote.

References:

Johansen NJ, Dejgaard TF, Lund A, et al. Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomized, double-blind placebo-controlled trial. The Lancet. 2020;8(4):313-324. doi: https://doi.org/10.1016/S2213-8587(20)30030-9.