Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled by Established Basal Insulin A 24-week, randomized, placebo-controlled comparison (GetGoal-l)

TLDR: By improving HbA1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.

Abstract: OBJECTIVE To examine the efficacy and safety of adding the once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide to established basal insulin therapy alone or together with metformin, in people with type 2 diabetes and elevated glycated hemoglobin (HbA 1c ). RESEARCH DESIGN AND METHODS A double-blind, parallel-group, placebo-controlled trial. Patients ( n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μg or placebo for 24 weeks. Basal insulin dosage was unchanged except to limit hypoglycemia. HbA 1c reduction from baseline was the primary end point. RESULTS Mean duration of diabetes was 12.5 years, duration of insulin use was 3.1 years, insulin dosage was 55 units/day, and baseline HbA 1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA 1c from baseline was –0.4% (95% CI –0.6 to –0.2; P = 0.0002), and mean HbA 1c at end point was 7.8%. HbA 1c P P P P = 0.012) were greater with lixisenatide. Main adverse events (AEs) with lixisenatide were gastrointestinal. Symptomatic hypoglycemia was 28% for lixisenatide and 22% for placebo; 4 of 328 subjects (1.2%) had severe hypoglycemia with lixisenatide vs. 0 of 167 with placebo. CONCLUSIONS By improving HbA 1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.