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.

Key words

diabetes - dipeptidyl peptidase-4 - DPP-IV inhibitor - PF-734200 - incretins

1 Clinical Trials Registration Number NCT00473525. Data in this paper were presented in abstract form at the 69 th Scientific Sessions of the American Diabetes Association; June 5 – 9, 2009; New Orleans, Louisiana, USA.

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1 Clinical Trials Registration Number NCT00473525. Data in this paper were presented in abstract form at the 69 th Scientific Sessions of the American Diabetes Association; June 5 – 9, 2009; New Orleans, Louisiana, USA.

Correspondence