Literature DB >> 20977584

A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes.

E J Rhee1, W Y Lee, K H Yoon, S J Yoo, I K Lee, S H Baik, Y K Kim, M K Lee, K S Park, J Y Park, B S Cha, H W Lee, K W Min, H Y Bae, M J Kim, J A Kim, D K Kim, S W Kim.   

Abstract

AIM: The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase-4 (DPP-IV) inhibitor, LC15-0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise.
METHODS: This study was a double-blind, randomized, multicenter and parallel-group, dose-range finding study. We enrolled 145 patients (91 men and 54 women) with a median age of 53 years and a median body mass index of 25.1 kg/m(2) . The median baseline fasting plasma glucose (FPG) was 8.1 mmol/l, the median HbA1c was 7.9% and the median time since the diagnosis of diabetes was 3 years. After 2 weeks of an exercise/diet programme followed by 2 weeks of a placebo period, the subjects were randomized to one of the four following groups for a 12-week active treatment period: placebo and 50, 100 or 200 mg of LC15-0444.
RESULTS: All three doses of LC15-0444 significantly reduced the HbA1c from baseline compared to the placebo group (-0.06 vs. -0.98, -0.74 and -0.78% in the placebo and 50, 100 and 200 mg groups, respectively), without a significant difference between the doses. Subjects with a higher baseline HbA1c (≥8.5%) had a greater reduction in HbA1c. Insulin secretory function, as assessed using homeostasis model assessment-beta cell, C-peptide and the insulinogenic index, improved significantly with LC15-0444 treatment. Insulin sensitivity, as assessed using homeostasis model assessment-insulin resistance, also improved significantly after 12 weeks of treatment. The 50 and 200 mg groups had significantly reduced total cholesterol and low-density lipoprotein cholesterol levels at 12 weeks compared to the placebo group. No dosage of LC15-0444 affected weight or waist circumference. The incidences of adverse events were similar in all study subjects.
CONCLUSIONS: LC15-0444 monotherapy (50 mg for 12 weeks) improved the HbA1c, FPG level, oral glucose tolerance test results, β-cell function and insulin sensitivity measures, and was well tolerated in Korean subjects with type 2 diabetes.
© 2010 Blackwell Publishing Ltd.

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Year:  2010        PMID: 20977584     DOI: 10.1111/j.1463-1326.2010.01303.x

Source DB:  PubMed          Journal:  Diabetes Obes Metab        ISSN: 1462-8902            Impact factor:   6.577


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