title: Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial.
abstract: To 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 <0.4% [<4.4 mmol/mol]) in HbA1c reduction with lixisenatide versus glulisine once daily, and either 2a) noninferiority in HbA1c reduction for lixisenatide versus glulisine thrice daily or 2b) superiority in body weight change for lixisenatide versus glulisine thrice daily. Fasting and postprandial plasma glucose, composite efficacy/safety end points, and adverse events were also assessed.
  
  
  
  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.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: University of Lorraine and the Department of Diabetology, Metabolic Diseases and Nutrition, Brabois Adult Hospital, Vandœuvre-lès-Nancy, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Guerci
authors.affiliation: GWT-TUD, Study Centre Prof. Hanefeld, Dresden Technical University, Dresden, Germany.
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
authors.affiliation: Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Gentile
authors.affiliation: LMC Diabetes & Endocrinology, Toronto, Ontario, Canada.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Aronson
authors.affiliation: Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Institute of Health and Hospital Virgen de la Victoria, Malaga, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: Sanofi, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Roy-Duval
authors.affiliation: Sanofi, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Souhami
authors.affiliation: Sanofi, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Wardecki
authors.affiliation: Sanofi, Bridgewater, NJ.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ye
authors.affiliation: Sanofi, Bridgewater, NJ.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Perfetti
authors.affiliation: Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield, U.K.
authors.forename: Simon
authors.initials: S
authors.lastname: Heller
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D000069036:Insulin Glargine / Q000008:administration & dosage*; D008297:Male; D062407:Meals; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D050177:Overweight / Q000150:complications; D010455:Peptides / Q000008:administration & dosage*; D019518:Postprandial Period; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D008687:Metformin; D010455:Peptides; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor