Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis. Issue 3 (September 2016)

• Record Type: Journal Article
• Authors: Ahrén, Bo; Galstyan, Gagik; Gautier, Jean-Francois; Giorgino, Francesco; Gomez-Peralta, Fernando; Krebs, Michael; Nikonova, Elena; Stager, William; Vargas-Uricoechea, Hernando
• Is Part Of: Diabetes therapy. Volume 7:Issue 3(2016)
• Page Start: 583
• Page End: 590
• Publication Date: 2016-09
• Subjects: Glucagon -- Glucagon-like peptide-1 receptor agonist -- Glycemic control -- Lixisenatide -- Prandial -- Type 2 diabetes mellitus; Diabetes -- Periodicals; Diabetes -- Treatment -- Periodicals; Endocrinology -- Periodicals; 616.462005
• DOI: 10.1007/s13300-016-0179-6
• Languages: English
• ISSNs: 1869-6961

Abstract

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).