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Postprandial hyperglycemia was ameliorated by taking metformin 30 min before a meal than taking metformin with a meal; a randomized, open-label, crossover pilot study

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Abstract

Taking metformin with a meal has been shown to decrease bioavailability of metformin. We hypothesized that taking metformin 30 min before a meal improves glucose metabolism. As an animal model, 18 Zucker-rats were divided into three groups as follows: no medication (Control), metformin (600 mg/kg) with meal (Met), and metformin 10 min before meal (pre-Met). In addition, five diabetic patients were recruited and randomized to take metformin (1000 mg) either 30 min before a meal (pre-Met protocol) or with a meal (Met protocol). In the animal model, the peak glucose level of pre-Met (7.8 ± 1.5 mmol/L) was lower than that of Control (12.6 ± 2.5 mmol/L, P = 0.010) or Met (14.1 ± 2.9 mmol/L, P = 0.020). Although there was no statistical difference among the three groups, total GLP-1 level at t = 0 min of pre-Met (7.4 ± 2.7 pmol/L) tended to be higher than that of Control (3.7 ± 2.0 pmol/L, P = 0.030) or Met (3.9 ± 1.2 pmol/L, P = 0.020). In diabetic patients, the peak glucose level of pre-Met protocol (7.0 ± 0.4 mmol/L) was lower than that of Met protocol (8.5 ± 0.9 mmol/L, P = 0.021). Total GLP-1 level at t = 30 min of pre-Met protocol (11.0 ± 6.1 pmol/L) was higher than that of Met protocol (6.7 ± 3.9 pmol/L, P = 0.033). Taking metformin 30 min before a meal ameliorated postprandial hyperglycemia. This promises to be a novel approach for postprandial hyperglycemia.

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Abbreviations

GLP-1:

Glucagon-like peptide-1

DPP-4:

Dipeptidyl peptidase 4

Control:

No medication

Met:

Taking metformin (600 mg/kg) with meal

pre-Met:

Taking metformin 10 min before meal

pre-Met protocol:

Taking metformin (1000 mg) 30 min before a meal

Met protocol:

Taking metformin (1000 mg) with a meal

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Author contributions

Y.H. originated and designed the study, researched data, and wrote manuscript. M.T. originated and designed the study, researched data, contributed to discussion, and reviewed the manuscript. H.O., K.M., T.K., N.K., T.F., S.M., Y.F., Y.T., S.Y., T.S., M.H., M.A., M.Y., Y.O., and G.H. researched data and contributed to discussion. N.N. and M.F. researched data and reviewed and edited the manuscript. M.F. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors critically reviewed the article and approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yoshitaka Hashimoto, Muhei Tanaka, Kazuteru Mistuhashi, Toshihiro Kimura, Noriyuki Kitagawa, Takuya Fukuda, Saori Majima, Yukiko Fukuda, Yoshimitsu Tanaka, Takafumi Senmaru, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Yohei Oda, Naoto Nakamura & Michiaki Fukui

  2. Division of Metabolism, Nephrology and Rheumatology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Hiroshi Okada & Goji Hasegawa

  3. Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Shunji Yamada

Authors
  1. Yoshitaka Hashimoto
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  2. Muhei Tanaka
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  9. Yukiko Fukuda
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  13. Masahide Hamaguchi
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  14. Mai Asano
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  15. Masahiro Yamazaki
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  18. Naoto Nakamura
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  19. Michiaki Fukui
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Corresponding author

Correspondence to Michiaki Fukui.

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Hashimoto, Y., Tanaka, M., Okada, H. et al. Postprandial hyperglycemia was ameliorated by taking metformin 30 min before a meal than taking metformin with a meal; a randomized, open-label, crossover pilot study. Endocrine 52, 271–276 (2016). https://doi.org/10.1007/s12020-015-0786-4

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  • DOI: https://doi.org/10.1007/s12020-015-0786-4

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