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Pharmacokinetic and Pharmacodynamic Interaction Between Gemigliptin and Metformin in Healthy Subjects

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Abstract

Background and Objective

Gemigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus. This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability.

Methods

A randomized, open-label, multiple-dose, three-treatment, three-period, three-sequence crossover study was conducted in healthy male subjects. Twenty-seven subjects received gemigliptin (50 mg once daily), metformin (1,000 mg twice a day), or both drugs for 7 days per dosing period. Blood samples were drawn over 24 h on the seventh day of each period for pharmacokinetic and pharmacodynamic evaluations, including plasma DPP-4 activity and total/active glucagon-like peptide-1 (GLP-1) levels. Meal tolerance tests were conducted for pharmacodynamic assessment on the eighth day. Safety and tolerability were evaluated using adverse events, vital signs, ECGs, and clinical laboratory tests.

Results

Coadministration of gemigliptin and metformin had no significant effect on the pharmacokinetics of gemigliptin or metformin. The inhibition of DPP-4 by gemigliptin was not affected by coadministration with metformin. Co-therapy of gemigliptin and metformin showed additional effects by increasing plasma active GLP-1 concentrations and lowering serum glucose levels. The plasma glucagon level was lower in co-therapy than with metformin monotherapy. The coadministration of gemigliptin and metformin was well-tolerated without serious adverse events.

Conclusions

Coadministration of gemigliptin and metformin showed beneficial anti-diabetic effects without pharmacokinetic drug–drug interactions.

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Acknowledgments

This study was sponsored by LG Life Sciences, Ltd. Korea. Dongseong Shin is supported by a training program grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare Affairs, Republic of Korea (A070001). Young Min Cho has received a lecture fee or a consultation fee from LG Life Sciences. Jeong-Ae Kim and Ji-Yung Ahn are employees of LG Life Sciences. The other authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea

    Dongseong Shin, SeungHwan Lee, Kyoung Soo Lim, Joo-Youn Cho, Howard Lee, In-Jin Jang & Kyung-Sang Yu

  2. Department of Internal Medicine, Seoul National University College of Medicine and Hospital, Seoul, Korea

    Young Min Cho

  3. LG Life Sciences, Ltd., Seoul, Korea

    Jeong-Ae Kim & Ji-Yung Ahn

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  1. Dongseong Shin
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Correspondence to Kyung-Sang Yu.

Additional information

ClinicalTrials.gov registry number: NCT01426399.

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Shin, D., Cho, Y.M., Lee, S. et al. Pharmacokinetic and Pharmacodynamic Interaction Between Gemigliptin and Metformin in Healthy Subjects. Clin Drug Investig 34, 383–393 (2014). https://doi.org/10.1007/s40261-014-0184-3

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