title: Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.
abstract: OBJECTIVE
  Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration.
  
  
  METHODS
  In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day).
  
  
  RESULTS
  Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (-2.5 vs. +2.1 kg; P < 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro.
  
  
  CONCLUSIONS
  Adding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.
authors.affiliation: Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Diabetes Center, Bad Lauterberg, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.affiliation: Eli Lilly and Company, Houten, the Netherlands.
authors.forename: Rimma
authors.initials: R
authors.lastname: Shaginian
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: James K
authors.initials: JK
authors.lastname: Malone
authors.affiliation: Eli Lilly and Company, Windlesham, U.K.
authors.forename: Simon
authors.initials: S
authors.lastname: Cleall
authors.affiliation: Eli Lilly and Company, Windlesham, U.K.
authors.forename: Matthew
authors.initials: M
authors.lastname: Reaney
authors.affiliation: Eli Lilly and Company, Houten, the Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: de Vries
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Byron J
authors.initials: BJ
authors.lastname: Hoogwerf
authors.affiliation: Bristol-Myers Squibb Company, San Diego, CA.
authors.forename: Leigh
authors.initials: L
authors.lastname: MacConell
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands bwo@umcg.nl.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000009:adverse effects; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D062407:Meals; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D018027:Receptors, Glucagon / Q000819:agonists*; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D008687:Metformin; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human