Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data

Abstract

Background: To examine the impact on glycemic control of achieving postprandial glucose (PPG) target with lixisenatide, a once-daily glucagon-like peptide-1 receptor agonist approved in the US, in patients with uncontrolled type 2 diabetes (T2D) on basal insulin, an agent that primarily targets fasting plasma glucose.

Methods: A post hoc pooled analysis was conducted using clinical trial data extracted from the intent-to-treat subpopulation of patients with T2D who participated in the 24-week, phase 3, randomized, double-blind, placebo-controlled, 2-arm parallel-group, multicenter GetGoal-L (NCT00715624), GetGoal-Duo 1 (NCT00975286) and GetGoal-L Asia trials (NCT00866658).

Results: Data from 587 lixisenatide-treated patients and 484 placebo-treated patients were included. Patients on lixisenatide were more likely to achieve a PPG target of < 10 mmol/L (< 180 mg/dL) than placebo-treated patients (P < 0.001), regardless of baseline fasting plasma glucose (FPG) levels. More importantly, those who reached the PPG target experienced a significantly greater reduction in mean HbA1c, were more likely to achieve HbA1c target of < 53 mmol/mol (< 7.0%), and experienced weight loss. Those outcomes were achieved with no significant differences in the risk of symptomatic hypoglycemia compared with placebo.

Conclusion: Compared with placebo, addition of lixisenatide to basal insulin improved HbA1c and reduced PPG, without increasing hypoglycemia risk. These findings highlight the importance of PPG control in the management of T2D, and provide evidence that adding an agent to basal insulin therapy that also impacts PPG has therapeutic value for patients who are not meeting glycemic targets.

Trial registration: NCT00715624. Registered 15 July 2008, NCT00975286. Registered 11 September 2009, NCT00866658. Registered 20 March 2009.

Keywords: Glucagon-like peptide-1 receptor; Glycemic targets; Lixisenatide; Post-prandial glucose; Type 2 diabetes.

Fig. 1

Percentage of patients who achieved ADA-recommended PPG target < 10 mmol/L (< 180 mg/dL) at Week 24. Abbreviations: ADA American Diabetes Association, FPG fasting plasma glucose, PPG postprandial glucose

Fig. 2

Change in HbA1c from baseline to Week 24. a Patients with controlled baseline FPG. b Patients with uncontrolled baseline FPG. Abbreviations: HbA1c glycated hemoglobin, FPG fasting plasma glucose, PPG postprandial glucose. ^aP = 0.008. ^bP < 0.001 for comparison between PPG response categories for both baseline FPG categories; Cochran–Mantel–Haenszel test stratified by study

Fig. 3

Percentage of patients with controlled (a) and uncontrolled (b) baseline FPG achieving HbA1c < 53 mmol/mol (< 7.0%) at Week 24. Abbreviations: HbA1c glycated hemoglobin, FPG fasting plasma glucose, PPG postprandial glucose. ^aP < 0.001 for comparison between PPG response categories