Lixisenatide and Liraglutide pharmacodynamic effects compared in T2DM patients on insulin glargine

Type 2 Diabetes Mellitus (T2DM) often progresses despite basal insulin therapy, like insulin glargine, requiring additional agents to achieve optimal glycemic control. Many patients struggle with post-prandial glucose excursions, which contribute significantly to overall glycemic burden and cardiovascular risk. Current standard-of-care often involves adding oral agents or other injectables. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of drugs that enhance glucose-dependent insulin secretion, suppress glucagon, and slow gastric emptying, making them effective for managing T2DM. This study aims to compare two established GLP-1R agonists, lixisenatide and liraglutide, in this challenging patient population.

This open-label, randomized, three-parallel-group study enrolled 142 T2DM patients whose condition was not adequately controlled with insulin glargine (with or without metformin). Participants were assigned to one of three 8-week treatment arms: Lixisenatide 20 μg (escalating from 10 μg QD SC for 2 weeks to 20 μg QD SC for 6 weeks), Liraglutide 1.2 mg (escalating from 0.6 mg QD SC for 1 week to 1.2 mg QD SC for 7 weeks), or Liraglutide 1.8 mg (escalating from 0.6 mg QD SC for 1 week, then 1.2 mg QD SC for 1 week, then 1.8 mg QD SC for 6 weeks). All treatments were administered subcutaneously (SC) once daily under fasted conditions, on top of existing insulin glargine (adjusted to maintain fasting self-measured plasma glucose between 4.4-5.6 mmol/L or 80-100 mg/dL) and stable metformin if applicable. The primary endpoint was the reduction in post-prandial plasma glucose (PPG) area under the curve (AUC) after a standardized meal.