Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1)

AimsTo assess the efficacy and safety of one- and two-step dose-increase regimens of lixisenatide once daily in participants with Type2 diabetes mellitus insufficiently controlled with metformin. MethodsThis was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre study enrolling participants with Type2 diabetes (n=484) treated with metformin. Participants were randomized to receive either lixisenatide in a one-step dose increase or a two-step dose increase vs. placebo for 24weeks, followed by a 52-week variable double blind period. Primary outcome was HbA(1c) reduction at week24. ResultsLixisenatide one-/two-step once daily significantly improved HbA(1c) at week24 compared with placebo (P<0.0001) and allowed more participants to achieve HbA(1c) <53mmol/mol (<7.0%) (P0.0005). Improvements were observed in fasting plasma glucose (-0.5/-0.6 vs. +0.1mmol/l; P<0.001) and body weight (-2.6/-2.7 vs. -1.6kg; P<0.005). At week24, adverse events were reported by 67.7/70.8/65.6% of participants treated with lixisenatide one-/two-step/placebo, respectivelynausea and vomiting being reported most frequently. Symptomatic hypoglycaemia occurred in 1.9/2.5% of participants on one-/two-step lixisenatide and 0.6% with placebo, with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable double-blind extension period of at least 52weeks. ConclusionsLixisenatide one- or two-step dose-increase regimens significantly improved glycaemic control and decreased body weight over 24weeks and during a long-term extension period without increasing hypoglycaemia. The study confirmed that tolerability in the one-step group was at least similar to the two-step dose increase, with nausea/vomiting and hypoglycaemia frequency being lower in the one-step regimen.