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

Bo Ahrén, Gagik Galstyan, Jean-Francois Gautier, Francesco Giorgino, Fernando Gomez-Peralta, Michael Krebs, Elena Nikonova, William Stager, Hernando Vargas-Uricoechea, Bo Ahrén, Gagik Galstyan, Jean-Francois Gautier, Francesco Giorgino, Fernando Gomez-Peralta, Michael Krebs, Elena Nikonova, William Stager, Hernando Vargas-Uricoechea

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.

Figures

Fig. 1
Fig. 1
Correlation between change in postprandial glucagon and change in a postprandial glucose and b HbA1c in the lixisenatide treatment arm and the placebo arm at Week 24. CI Confidence interval

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Source: PubMed

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