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


CONCLUSIONS
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.


BACKGROUND
Sanofi.


BACKGROUND
NCT00712673 (GetGoal-M) and NCT00713830 (GetGoal-S).
Lund University, Lund, Sweden. bo.ahren@med.lu.se.
Bo
B
Ahrén
National Centre of Endocrinology, Moscow, Russian Federation.
Gagik
G
Galstyan
Lariboisière Hospital, Paris, France.
Jean-Francois
JF
Gautier
University of Bari Aldo Moro, Bari, Italy.
Francesco
F
Giorgino
Hospital General de Segovia, Segovia, Spain.
Fernando
F
Gomez-Peralta
Medical University of Vienna, Vienna, Austria.
Michael
M
Krebs
Artech Information Systems, LLC, Morristown, NJ, USA.
Elena
E
Nikonova
Sanofi, Bridgewater, NJ, USA.
William
W
Stager
Hospital Universitario San José, Popayán, Colombia.
Hernando
H
Vargas-Uricoechea
Glucagon; Glucagon-like peptide-1 receptor agonist; Glycemic control; Lixisenatide; Prandial; Type 2 diabetes mellitus