title: Safety and efficacy of saxagliptin in combination with submaximal sulphonylurea versus up-titrated sulphonylurea over 76 weeks.
abstract: To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled on sulphonylurea monotherapy, 768 patients were randomised to saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg versus placebo added to up-titrated glyburide over 76 weeks (24 weeks plus 52-week extension) in this phase 3, double-blind, placebo-controlled trial; 557 patients completed the study, 142 without being rescued. At 76 weeks, adjusted mean changes from baseline HbA(1C) (repeated measures model) (95% confidence interval) for saxagliptin 2.5 mg, saxagliptin 5 mg, and up-titrated glyburide were 0.11% (-0.05, 0.27), 0.03% (-0.14, 0.19), and 0.69% (0.47, 0.92), respectively (post hoc and nominal p < 0.0001 for saxagliptin 2.5 and 5 mg vs. up-titrated glyburide). Adverse event frequency was similar in all treatment groups; reported hypoglycaemia event rates were 24.2%, 22.9%, and 20.6% with saxagliptin 2.5 mg, saxagliptin 5 mg, and up-titrated glyburide, respectively. Saxagliptin plus glyburide provided sustained incremental efficacy compared with up-titrated glyburide over 76 weeks, and was generally well tolerated.
authors.affiliation: Federal University of São Paulo, Diabetes Center, Brazil.
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Chacra
authors.forename: Gerry H
authors.initials: GH
authors.lastname: Tan
authors.forename: Shoba
authors.initials: S
authors.lastname: Ravichandran
authors.forename: James
authors.initials: J
authors.lastname: List
authors.forename: Roland
authors.initials: R
authors.lastname: Chen
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000218:Adamantane; D015415:Biomarkers; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human; C502994:saxagliptin