Relationship between changes in postprandial glucagon, patient characteristics, and response to lixisenatide as add-on to oral antidiabetics

Background and aims: Lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, reduces postprandial (PP) glycaemic excursions and HbA 1c . We report an exploratory analysis of the GetGoal-M and S trials in patients with type 2 diabetes mellitus (T2DM) with different changes in PP glucagon levels in response to lixisenatide treatment. Materials and methods: Patients (n=423) were stratified by their change in 2 hour PP glucagon level between baseline evaluation and Week 24 of treat - ment with lixisenatide as add-on to oral antidiabetics (OADs) into groups of Greater Change (GC; n=213) or Smaller Change (SC; n=210) in plasma glucagon levels (median change -23.57 ng/L). ANOVA and Chi-squared tests were used for the comparison of continuous and categorical variables, respec - tively. Baseline and endpoint continuous measurements in each group were compared using paired t -tests. Results: Mean change from baseline in 2 hour PP glucagon levels for the GC vs SC groups was -47.19 vs -0.59 ng/L (p<0.0001), respectively. Patients in the GC group had a shorter mean duration of diabetes (7.3 vs 9.0 years; p=0.0036) and lesser OAD use (4.5 vs 5.7 years; p=0.0092) than those in the SC group. Patients in the GC group had a greater mean reduction in HbA 1c (-1.10 vs -0.67%; p<0.0001), fasting plasma glucose (FPG; -25.20 vs -9.30 mg/dL [p<0.0001]), PP plasma glucose (PPG; -129.40 vs -78.22 mg/dL [p<0.0001]), and a greater drop in weight (-2.27 vs -1.17 kg; p=0.0002) and body mass index (-0.84 vs -0.44 kg/m 2 ; p=0.0002) than those in the SC group. More patients in the GC group also achieved composite endpoints, including HbA 1c <7% with no symptomatic hypoglycaemia and no weight gain (40.38 vs 19.52%; p<0.0001), than in the SC group. Conclusion: Greater reductions in PP glucagon associated with lixisenatide as add-on to OADs in patients with T2DM are also associated with greater reductions in HbA1c, FPG, PPG, and greater weight loss, highlighting the importance of glucagon suppression on therapeutic response. Clinical Trial Registration Number: NCT00712673; NCT00713830 Supported by: Sanof