title: GLP-1 RAs as compared to prandial insulin after failure of basal insulin in type 2 diabetes: lessons from the 4B and Get-Goal DUO 2 trials.
abstract: The add-on of a prandial (short-acting) GLP-1 RA to basal insulin in subjects with T2DM who fail to control A1C on basal insulin, stems from the physiological principles of post-prandial glucose homeostasis, and it is based on evidence from clinical trials. The 4B and GetGoal DUO 2 studies are the first to establish in head-to-head comparison, the efficacy and safety of short-acting GLP-1 RAs vs prandial insulin, when added-on to basal insulin glargine. In the 4B study (exenatide 2/d vs lispro 3/d) exenatide demonstrated similar efficacy vs lispro in reducing A1C to ~7.2%. However, exenatide reduced also body weight and hypoglycemia incidence as compared to lispro. In GetGoal DUO 2, the head-to-head comparison was between lixisenatide 1/d vs glulisine either 1/d (at the main meal, basal-plus) or 3/d (basal-bolus). Like in 4B, in GetGoal DUO 2 the A1C decreased to similar values with lixisenatide or glulisine 1/d (~7.2%), or glulisine 3/d (~7.0%). Again, as in the 4B, body weight and hypoglycemia incidence were lower with lixisenatide. In both studies a similar percentage of subjects reached the A1C <7.0% on GLP-1 RA or prandial insulin. A higher percentage of subjects reported adverse events on GLP-1 RAs, primarily gastrointestinal related. The studies 4B and GetGoal DUO 2 suggest that after failure of basal insulin in T2DM, the add-on of prandial GLP-1 RA is as effective as prandial insulin in lowering A1C, with added benefits of reducing body weight and risk for hypoglycemia. In addition, the GLP-1 RA + basal insulin is a simpler therapeutic option as compared to basal-plus and basal-bolus regimens.
authors.affiliation: Section of Internal Medicine, Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Porcellati
authors.affiliation: Section of Internal Medicine, Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lucidi
authors.affiliation: Section of Internal Medicine, Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Italy. Electronic address: geremia.bolli@unipg.it.
authors.forename: G B
authors.initials: GB
authors.lastname: Bolli
authors.affiliation: Section of Internal Medicine, Endocrinology and Metabolism, Department of Medicine, Perugia University School of Medicine, Italy.
authors.forename: C G
authors.initials: CG
authors.lastname: Fanelli
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D000069036:Insulin Glargine / Q000008:administration & dosage; D010347:Patient Care Planning; D010455:Peptides / Q000008:administration & dosage; D019518:Postprandial Period; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D014688:Venoms / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000069036:Insulin Glargine; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: GLP-1 receptor agonists; basal insulin; exenatide; lixisenatide