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

Ahrén, Bo LU ; Galstyan, Gagik; Gautier, Jean Francois; Giorgino, Francesco; Gomez-Peralta, Fernando; Krebs, Michael; Nikonova, Elena; Stager, William and Vargas-Uricoechea, Hernando (2016) In Diabetes Therapy 7(3). p.583-590
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... (More)

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).

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glucagon, Glucagon-like peptide-1 receptor agonist, Glycemic control, Lixisenatide, Prandial, Type 2 diabetes mellitus
in
Diabetes Therapy
volume
7
issue
3
pages
8 pages
publisher
Springer
external identifiers
  • scopus:84986201026
  • wos:000382882000017
ISSN
1869-6953
DOI
10.1007/s13300-016-0179-6
language
English
LU publication?
yes
id
991ff9cc-bb35-467e-96e0-a9d6601c78f7
date added to LUP
2016-12-13 11:20:00
date last changed
2017-08-27 06:31:50
@article{991ff9cc-bb35-467e-96e0-a9d6601c78f7,
  abstract     = {<p>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 (HbA<sub>1c</sub>) 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 HbA<sub>1c</sub>. Results: Lixisenatide reduced 2-h postprandial glucagon at Week 24 compared with placebo (P &lt; 0.00001). The mean change in postprandial glucagon significantly correlated with reductions in postprandial glucose (P &lt; 0.00001) and HbA<sub>1c</sub> (P &lt; 0.00001). Conclusion: A reduction in postprandial glucagon following lixisenatide administration correlated with a decrease in postprandial glucose and HbA<sub>1c</sub> 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).</p>},
  author       = {Ahrén, Bo and Galstyan, Gagik and Gautier, Jean Francois and Giorgino, Francesco and Gomez-Peralta, Fernando and Krebs, Michael and Nikonova, Elena and Stager, William and Vargas-Uricoechea, Hernando},
  issn         = {1869-6953},
  keyword      = {Glucagon,Glucagon-like peptide-1 receptor agonist,Glycemic control,Lixisenatide,Prandial,Type 2 diabetes mellitus},
  language     = {eng},
  month        = {09},
  number       = {3},
  pages        = {583--590},
  publisher    = {Springer},
  series       = {Diabetes Therapy},
  title        = {Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus : A Post Hoc Analysis},
  url          = {http://dx.doi.org/10.1007/s13300-016-0179-6},
  volume       = {7},
  year         = {2016},
}