title: Efficacy and safety of the once-weekly GLP-1 receptor agonist albiglutide versus sitagliptin in patients with type 2 diabetes and renal impairment: a randomized phase III study.
abstract: OBJECTIVE
  To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications.
  
  
  METHODS
  In this phase III, randomized, double-blind, multicenter, 52-week study, the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment, as assessed with estimated glomerular filtration rate and categorized as mild, moderate, or severe (≥60 to ≤89, ≥30 to ≤59, and ≥15 to ≤29 mL/min/1.73 m(2), respectively). Secondary end points included fasting plasma glucose (FPG), weight, achievement of treatment targets, hyperglycemic rescue, and safety.
  
  
  RESULTS
  Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years, BMI of 30.4 kg/m(2), HbA1c of 8.2% (66 mmol/mol), and diabetes disease duration of 11.2 years. HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin (-0.83% vs. -0.52%, P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin (P = 0.0017). Results of safety assessments were similar between groups, and most adverse events (AEs) were mild or moderate. The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall, 31.7%, 25.2%; diarrhea, 10.0%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%, 1.2%, respectively.
  
  
  CONCLUSIONS
  Once-weekly albiglutide therapy in renally impaired patients with type 2 diabetes provided statistically superior glycemic improvement with almost similar tolerability compared with daily sitagliptin therapy.
authors.affiliation: Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada leiterl@smh.ca.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: GlaxoSmithKline, King of Prussia, PA.
authors.forename: Molly C
authors.initials: MC
authors.lastname: Carr
authors.affiliation: GlaxoSmithKline, King of Prussia, PA.
authors.forename: Murray
authors.initials: M
authors.lastname: Stewart
authors.affiliation: GlaxoSmithKline, King of Prussia, PA.
authors.forename: Angela
authors.initials: A
authors.lastname: Jones-Leone
authors.affiliation: GlaxoSmithKline, Uxbridge, Middlesex, U.K.
authors.forename: Rhona
authors.initials: R
authors.lastname: Scott
authors.affiliation: GlaxoSmithKline, King of Prussia, PA.
authors.forename: Fred
authors.initials: F
authors.lastname: Yang
authors.affiliation: Metabolic Institute of America, Tarzana, CA.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Handelsman
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D018027:Receptors, Glucagon / Q000819:agonists*; D051437:Renal Insufficiency / Q000097:blood / Q000188:drug therapy*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D011719:Pyrazines; D018027:Receptors, Glucagon; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C000593833:GLP1R protein, human; C534611:rGLP-1 protein