Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine: A 24-week, randomized, placebo-controlled study (GetGoal-Duo 1)

OBJECTIVE: When oral therapy for type 2 diabetes is ineffective, adding basal insulin improves glycemic control. However, when glycated hemoglobin (HbA(1c)) remains elevated because of postprandial hyperglycemia, the next therapeutic step is controversial. We examined the efficacy and safety of lixisenatide in patients with HbA(1c) still elevated after initiation of insulin glargine. RESEARCH DESIGN AND METHODS: This double-blind, parallel-group trial enrolled patients with HbA(1c) 7–10% despite oral therapy. Insulin glargine was added and systematically titrated during a 12-week run-in, after which candidates with fasting glucose ≤7.8 mmol/L and HbA(1c) 7–9% were randomized to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued. The primary end point was HbA(1c) change after randomization. RESULTS: The randomized population (n = 446) had mean diabetes duration of 9.2 years, BMI 31.8 kg/m(2), and daily glargine dosage of 44 units. HbA(1c) had decreased during run-in from 8.6 to 7.6%; adding lixisenatide further reduced HbA(1c) by 0.71 vs. 0.40% with placebo (least squares mean difference, –0.32%; 95% CI, –0.46 to –0.17; P < 0.0001). More participants attained HbA(1c) <7% with lixisenatide (56 vs. 39%; P < 0.0001). Lixisenatide reduced plasma glucose 2 h after a standardized breakfast (difference vs. placebo –3.2 mmol/L; P < 0.0001) and had a favorable effect on body weight (difference vs. placebo –0.89 kg; P = 0.0012). Nausea, vomiting, and symptomatic hypoglycemia <3.3 mmol/L were more common with lixisenatide. CONCLUSIONS: Adding lixisenatide to insulin glargine improved overall and postprandial hyperglycemia and deserves consideration as an alternative to prandial insulin for patients not reaching HbA(1c) goals with recently initiated basal insulin.