Effects of JNJ-38431055, a novel GPR119 receptor agonist, in randomized, double-blind, placebo-controlled studies in subjects with type 2 diabetes

Diabetes Obes Metab. 2012 Aug;14(8):709-16. doi: 10.1111/j.1463-1326.2012.01587.x. Epub 2012 Mar 14.


Aim: G-protein coupled receptor agonists are currently under investigation for their potential utility in patients with type 2 diabetes mellitus (T2DM). The objective was to determine the pharmacokinetics, pharmacodynamics, safety and tolerability of GPR119 agonist, JNJ-38431055 in T2DM subjects.

Methods: This was a randomized, double-blind, placebo- and positive-controled, single-dose cross-over study and a randomized, double-blind, placebo-controled multiple-dose parallel design study. The study was conducted at 4 US research centres. Two different experiments involving 25 and 32 different subjects were performed in male and female subjects, aged 25-60 years, mean body mass index between 22 and 39.9 kg/m2 who had T2DM diagnosed 6 months to 10 years before screening. JNJ-38431055 (100 and 500 mg) or sitagliptin (100 mg) as a single-dose or JNJ-38431055 (500 mg) once daily for 14 consecutive days were tested. Effects on stimulated plasma glucose, insulin, C-peptide and incretin concentrations were pre-specified outcomes.

Results: JNJ-38431055 was well tolerated and not associated with hypoglycaemia. Plasma systemic exposure of JNJ-38431055 increased as the dose increased, was approximately two-fold greater after multiple-dose administration, and attained steady-state after approximately 8 days. Compared with placebo, single-dose administration of oral JNJ-38431055 decreased glucose excursion during an oral glucose tolerance test, but multiple-dose administration did not alter 24-h weighted mean glucose. Multiple dosing of JNJ-38431055 increased post-meal total glucagon-like peptide 1 and gastric insulinotropic peptide concentrations compared to baseline.

Conclusions: These studies provide evidence of limited glucose lowering and incretin activity for JNJ-38431055 in subjects with T2DM.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptide 1 / blood*
  • Glucagon-Like Peptide 1 / drug effects
  • Glucose Tolerance Test
  • Humans
  • Incretins / blood*
  • Male
  • Middle Aged
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacology*
  • Receptors, G-Protein-Coupled / agonists*
  • Sitagliptin Phosphate
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / pharmacology*


  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • GPR119 protein, human
  • Incretins
  • Pyrazines
  • Receptors, G-Protein-Coupled
  • Triazoles
  • Glucagon-Like Peptide 1
  • Sitagliptin Phosphate