Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L)

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 (HbA1c).

Research design and methods: We conducted 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. HbA1c 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 HbA1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA1c from baseline was -0.4% (95% CI -0.6 to -0.2; P = 0.0002), and mean HbA1c at end point was 7.8%. HbA1c <7.0% (53 mmol/mol) was attained by more lixisenatide (28%) than placebo (12%; P < 0.0001) participants. Lixisenatide reduced plasma glucose levels after a standardized breakfast (placebo-corrected reduction, -3.8 mmol/L; P < 0.0001); seven-point glucose profiles showed a reduction persisting through the day. Reductions in body weight (placebo corrected, -1.3 kg; P < 0.0001) and insulin dosage (-3.7 units/day; 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 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.

Trial registration: ClinicalTrials.gov NCT00975286.

Figure 1

Clinical responses to therapy from baseline to week 24 and end point with LOCF. A: Mean HbA_1c (%) by visit. B: Mean FPG (mmol/L) by visit. C: Mean change in body weight (kg) from baseline by visit. D: Mean daily basal insulin dose (units/day) by visit. Values are all mean ± SE, for the modified intent-to-treat population. All analyses excluded measurements after the introduction of rescue medication and/or after treatment cessation plus 3 days. For week 24 (LOCF), the analysis included measurements obtained up to 3 days after the last dose of study drug.

Figure 2

Mean seven-point SMPG (mmol/L). Mean ± SE seven-point SMPG (mmol/L) at baseline and week-24 LOCF in the modified intent-to-treat population for basal insulin + lixisenatide (A) and basal insulin + placebo (B).