Lixisenatide Significantly Increases the Probability of a A1C Response in Patients Not Adequately Controlled on Oral Antihyperglycemic Agents

Abstract

To evaluate the response to lixisenatide, a novel once-daily glucagon-like peptide-1 receptor agonist, as add on to 1 oral antihyperglycemic agent (OAA) and 2 OAAs in patients with type 2 diabetes mellitus (T2DM) and the patient characteristics that may predict a response. Data were extracted from 5 randomized, 24-week, double-blind, placebo-controlled trials of the efficacy and safety of lixisenatide in patients with T2DM with inadequate glycemic control: GetGoal-M, -F1, -S, -P and -M Asia. Response was defined as the proportion of patients achieving A1C <7% or an A1C reduction of ≥1%. Evaluated predictors of response were age, gender, race, diabetes duration and baseline A1C. Significantly more patients achieved A1C <7% with lixisenatide + 1 OAA vs. placebo (43.0 vs. 23.0%, respectively; p<0.0001) and with lixisenatide + 2 OAAs vs. placebo (42.1 vs. 18.0%, respectively; p<0.0001). Significantly more patients achieved a response with lixisenatide + 1 OAA vs. placebo (59.8 vs. 35.4%, respectively; p<0.0001) and lixisenatide + 2 OAAs vs. placebo (60.2% vs. 27.5%, respectively; p<0.0001). No baseline characteristics were a strong predictor of response. In multivariable regression analysis, lixisenatide + 1 OAA and lixisenatide + 2 OAAs was 4.17 times (95% CI: 3.21, 5.41) and 2.81 times (95% CI: 2.14, 3.70) more likely to produce a A1C response vs. placebo, respectively. Lixisenatide added to 1 OAA or 2 OAAs significantly improved A1C and led to a higher proportion of patients reaching A1C <7% or an A1C reduction of ≥1% vs. placebo.