title: Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro.
abstract: OBJECTIVE
  GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine.
  
  
  METHODS
  Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26.
  
  
  RESULTS
  At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).
  
  
  CONCLUSIONS
  Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.
authors.affiliation: Dallas Diabetes and Endocrine Center, Medical City Dallas Hospital, Dallas, TX juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Tulane University Health Sciences Center, New Orleans, LA.
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre and Universidade Federal do Sul, Porto Alegre, Brazil.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gross
authors.affiliation: Medstar Health Research Institute, Hyattsville, MD.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ratner
authors.affiliation: Department of Medicine, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.affiliation: The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Francis C C
authors.initials: FC
authors.lastname: Chow
authors.affiliation: GlaxoSmithKline, Upper Merion, PA.
authors.forename: Fred
authors.initials: F
authors.lastname: Yang
authors.affiliation: GlaxoSmithKline, Upper Merion, PA.
authors.forename: Diane
authors.initials: D
authors.lastname: Miller
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Johnson
authors.affiliation: GlaxoSmithKline, Upper Merion, PA.
authors.forename: Murray W
authors.initials: MW
authors.lastname: Stewart
authors.affiliation: Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D062407:Meals; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D000077205:Pioglitazone; D018027:Receptors, Glucagon / Q000819:agonists; D045162:Thiazolidinediones / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; 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; D000077205:Pioglitazone; D018027:Receptors, Glucagon; D045162:Thiazolidinediones; C000593833:GLP1R protein, human; C534611:rGLP-1 protein