Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in Type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S)

摘要

Aims To assess efficacy and safety of lixisenatide once-daily versus placebo in Type 2 diabetes mellitus (T2DM) patients inadequately controlled on sulfonylurea (SU) ± metformin. Methods In this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin. Primary outcome was change in HbA1c from baseline to Week 24. Results Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: - 0.85% vs. - 0.10%; p 0.0001) and more patients achieved HbA1c 7.0% (36.4% vs. 13.5%; p 0.0001). Lixisenatide significantly lowered FPG and body weight versus placebo. In breakfast meal test patients, lixisenatide reduced 2-hour PPG versus placebo (LS mean: - 111.48 vs. - 3.80 mg/dL [- 6.19 vs. - 0.21 mmol/L]; p 0.0001) and glucose excursion (- 94.11 vs. + 6.24 mg/dL [- 5.22 vs. + 0.35 mmol/L]), and reduced 2-hour glucagon, insulin, proinsulin, and C-peptide. The percentage of AEs was 68.3% for lixisenatide and 61.1% for placebo; and for SAEs: 3.5% versus 5.6%, respectively. Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo (15.3% vs. 12.3%, respectively); one severe episode of hypoglycemia was reported with lixisenatide. Conclusions Once-daily lixisenatide significantly improved glycemic control, with a pronounced postprandial effect, without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks.