Rosenstock, JulioGuerci, BrunoHanefeld, MarkolfGentile, SandroAronson, RonnieTinahones, Francisco JRoy-Duval, ChristineSouhami, ElisabethWardecki, MarekYe, JennyPerfetti, RiccardoHeller, SimonGetGoal Duo-2 Trial Investigators2023-01-252023-01-252016-05-23http://hdl.handle.net/10668/10120To provide evidence-based options on how to intensify basal insulin, we explored head-to-head prandial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulin glargine with or without 1-3 oral antidiabetic agents (OADs). Patients were randomized to lixisenatide once daily or insulin glulisine given once or thrice daily, added to glargine, with or without metformin, if HbA1c remained ≥7 to ≤9% (≥53 to ≤75 mmol/mol) after 12 weeks of glargine optimization with OADs other than metformin stopped at the start of optimization. Coprimary end points at 26 weeks were 1) noninferiority (95% CI upper bound Baseline characteristics were similar between arms (n = 298, diabetes and basal insulin duration of 12.2 and 3.2 years, respectively; BMI 32.2 kg/m(2)). HbA1c improved from 8.5% to 7.9% (69 to 63 mmol/mol) with glargine optimization and further to 7.2%, 7.2%, and 7.0% (55, 55, and 53 mmol/mol) with lixisenatide and glulisine once daily and thrice daily, respectively; all coprimary end points were met. Symptomatic hypoglycemia and body weight were lower in lixisenatide versus glulisine patients. More gastrointestinal events occurred with lixisenatide. Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option, attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes.enAgedBlood GlucoseBody Mass IndexBody WeightDiabetes Mellitus, Type 2Drug Therapy, CombinationEndpoint DeterminationFemaleGlucagon-Like Peptide-1 ReceptorGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulin GlargineMaleMealsMetforminMiddle AgedOverweightPeptidesPostprandial Periodresearch article2722251010.2337/dc16-00141935-5548