title: A Dose-Ranging Study of the DPP-IV Inhibitor PF-734200 Added to Metformin in Subjects With Type 2 Diabetes*.
abstract: The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin. Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were randomized to placebo or PF-734200 2 mg, 5 mg, 10 mg, or 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline and week 12. A total of 301 subjects were treated. At week 12, PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A (1C) (HbA (1c)) compared with placebo. The mean (95% confidence interval) placebo-adjusted changes in HbA (1c) were -0.31% (-0.70 to 0.08), -0.74% (-1.12 to -0.36), -0.70% (-1.02 to -0.38), and -0.75% (-1.07 to -0.43) for the 2 mg, 5 mg, 10 mg, and 20 mg doses, respectively. PF-734200 20 mg significantly reduced glucose area under the curve following MMTT (-12.8% [-22.9 to -2.7]; p=0.003) compared with placebo. The reductions observed with other doses were not statistically significant. PF-734200 was safe and well tolerated at all doses tested when added to metformin. PF-734200 safely and effectively lowered HbA (1c) in subjects receiving metformin. The 20 mg dose provided the greatest improvements in post-prandial glucose.
authors.affiliation: Pfizer Global Research and Development, New London, Connecticut, USA. steven.g.terra@pfizer.com
authors.forename: S G
authors.initials: SG
authors.lastname: Terra
authors.forename: V
authors.initials: V
authors.lastname: Somayaji
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: A J
authors.initials: AJ
authors.lastname: Lewin
authors.forename: J G
authors.initials: JG
authors.lastname: Teeter
authors.forename: H
authors.initials: H
authors.lastname: Dai
authors.forename: T T
authors.initials: TT
authors.lastname: Nguyen
authors.forename: R A
authors.initials: RA
authors.lastname: Calle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D011743:Pyrimidines; D011759:Pyrrolidines; D008687:Metformin; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; C558848:gosogliptin