Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono)

Abstract

Objective: To assess efficacy and safety of lixisenatide monotherapy in type 2 diabetes.

Research design and methods: Randomized, double-blind, 12-week study of 361 patients not on glucose-lowering therapy (HbA(1c) 7-10%) allocated to one of four once-daily subcutaneous dose increase regimens: lixisenatide 2-step (10 μg for 1 week, 15 μg for 1 week, and then 20 μg; n = 120), lixisenatide 1-step (10 μg for 2 weeks and then 20 μg; n = 119), placebo 2-step (n = 61), or placebo 1-step (n = 61) (placebo groups were combined for analyses). Primary end point was HbA(1c) change from baseline to week 12.

Results: Once-daily lixisenatide significantly improved HbA(1c) (mean baseline 8.0%) in both groups (least squares mean change vs. placebo: -0.54% for 2-step, -0.66% for 1-step; P < 0.0001). Significantly more lixisenatide patients achieved HbA(1c) <7.0% (52.2% 2-step, 46.5% 1-step) and ≤ 6.5% (31.9% 2-step, 25.4% 1-step) versus placebo (26.8% and 12.5%, respectively; P < 0.01). Lixisenatide led to marked significant improvements of 2-h postprandial glucose levels and blood glucose excursions measured during a standardized breakfast test. A significant decrease in fasting plasma glucose was observed in both lixisenatide groups versus placebo. Mean decreases in body weight (∼2 kg) were observed in all groups. The most common adverse events were gastrointestinal-nausea was the most frequent (lixisenatide 23% overall, placebo 4.1%). Symptomatic hypoglycemia occurred in 1.7% of lixisenatide and 1.6% of placebo patients, with no severe episodes. Safety/tolerability was similar for the two dose regimens.

Conclusions: Once-daily lixisenatide monotherapy significantly improved glycemic control with a pronounced postprandial effect (75% reduction in glucose excursion) and was safe and well tolerated in type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT00688701.

Figure 1

Changes in glycated hemoglobin (HbA_1c) levels after 12 weeks’ treatment with lixisenatide (according to dose increase regimen) or placebo. A: Mean change (±SEM) in HbA_1c over time. B: Percentage of patients achieving HbA_1c goals <7.0% and ≤6.5%. LOCF, Last Observation Carry Forward.

Figure 2

Changes in postbreakfast glucose parameters from baseline after 12-weeks' treatment with lixisenatide (according to dose increase regimen) or placebo. LS mean change in mean (±SEM) 2-h PPG levels is shown. LS mean change in 2-h glucose excursion is also shown. Data are from patients undergoing a standardized breakfast meal test at selected sites. Glucose excursion = 2-h PPG, plasma glucose 30 min before the meal test before study drug administration. Mean ± SD baseline values for 2-h PPG: 13.99 ± 4.78 mmol/L (placebo), 14.67 ± 3.78 mmol/L (lixisenatide 2-step), 14.55 ± 3.36 mmol/L (lixisenatide 1-step). Mean ± SD baseline values for glucose excursion: 4.72 ± 3.65 mmol/L (placebo), 5.45 ± 3.02 mmol/L (lixisenatide 2-step), 5.25 ± 2.89 mmol/L (lixisenatide 1-step). To convert mmol/L to mg/dL, divide by 0.0555.