Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis

  • Diabetes Ther. 2016 Sep;7(3):583-90. doi: 10.1007/s13300-016-0179-6.
Bo Ahrén  1 ,  Gagik Galstyan  2 ,  Jean-Francois Gautier  3 ,  Francesco Giorgino  4 ,  Fernando Gomez-Peralta  5 ,  Michael Krebs  6 ,  Elena Nikonova  7 ,  William Stager  8 ,  Hernando Vargas-Uricoechea  9
Affiliations
  • 1. Lund University, Lund, Sweden. [email protected].
  • 2. National Centre of Endocrinology, Moscow, Russian Federation.
  • 3. Lariboisière Hospital, Paris, France.
  • 4. University of Bari Aldo Moro, Bari, Italy.
  • 5. Hospital General de Segovia, Segovia, Spain.
  • 6. Medical University of Vienna, Vienna, Austria.
  • 7. Artech Information Systems, LLC, Morristown, NJ, USA.
  • 8. Sanofi, Bridgewater, NJ, USA.
  • 9. Hospital Universitario San José, Popayán, Colombia.
PMID: 27319011 DOI: 10.1007/s13300-016-0179-6
Abstract

Introduction: The extent to which postprandial glucagon reductions contribute to lowering of postprandial glucose in patients with type 2 diabetes mellitus (T2DM) is currently unknown. The aim of this analysis was to determine whether a reduction in postprandial glucagon following treatment with the glucagon-like peptide-1 receptor agonist lixisenatide correlates with a reduction in postprandial glucose and glycated Hemoglobin (HbA1c) in patients with T2DM.

Methods: A post hoc analysis was performed on pooled data from the modified intent-to-treat populations of two lixisenatide Phase 3 trials: GetGoal-M (lixisenatide versus placebo as add-on to metformin) and GetGoal-S (lixisenatide versus placebo as add-on to sulfonylurea [SU] ± metformin). Glucagon levels were assessed 2 h after a standardized meal test performed at baseline and Week 24 and were examined for correlation with changes in 2-h postprandial glucose and HbA1c.

Results: Lixisenatide reduced 2-h postprandial glucagon at Week 24 compared with placebo (P < 0.00001). The mean change in postprandial glucagon significantly correlated with reductions in postprandial glucose (P < 0.00001) and HbA1c (P < 0.00001).

Conclusion: A reduction in postprandial glucagon following lixisenatide administration correlated with a decrease in postprandial glucose and HbA1c in patients with T2DM insufficiently controlled on metformin and/or SU. This suggests that lowering of postprandial glucagon contributes to the overall glycemic improvement observed with lixisenatide.

Funding: Sanofi.

Clinical trial numbers: NCT00712673 (GetGoal-M) and NCT00713830 (GetGoal-S).

Keywords
Glucagon; Glucagon-like peptide-1 receptor agonist; Glycemic control; Lixisenatide; Prandial; Type 2 diabetes mellitus.