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Endocrine

, Volume 52, Issue 2, pp 271–276 | Cite as

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

  • Yoshitaka Hashimoto
  • Muhei Tanaka
  • Hiroshi Okada
  • Kazuteru Mistuhashi
  • Toshihiro Kimura
  • Noriyuki Kitagawa
  • Takuya Fukuda
  • Saori Majima
  • Yukiko Fukuda
  • Yoshimitsu Tanaka
  • Shunji Yamada
  • Takafumi Senmaru
  • Masahide Hamaguchi
  • Mai Asano
  • Masahiro Yamazaki
  • Yohei Oda
  • Goji Hasegawa
  • Naoto Nakamura
  • Michiaki FukuiEmail author
Original Article

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.

Keywords

Postprandial hyperglycemia Metformin Biguanides Type 2 diabetes Glucagon-like peptide-1 (GLP-1) Incretin Gastric emptying 

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

Notes

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.

Compliance with ethical standards

Conflict of interest

No potential conflict of interest relevant to this article was reported.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yoshitaka Hashimoto
    • 1
  • Muhei Tanaka
    • 1
  • Hiroshi Okada
    • 2
  • Kazuteru Mistuhashi
    • 1
  • Toshihiro Kimura
    • 1
  • Noriyuki Kitagawa
    • 1
  • Takuya Fukuda
    • 1
  • Saori Majima
    • 1
  • Yukiko Fukuda
    • 1
  • Yoshimitsu Tanaka
    • 1
  • Shunji Yamada
    • 3
  • Takafumi Senmaru
    • 1
  • Masahide Hamaguchi
    • 1
  • Mai Asano
    • 1
  • Masahiro Yamazaki
    • 1
  • Yohei Oda
    • 1
  • Goji Hasegawa
    • 2
  • Naoto Nakamura
    • 1
  • Michiaki Fukui
    • 1
    Email author
  1. 1.Department of Endocrinology and Metabolism, Kyoto Prefectural University of MedicineGraduate School of Medical ScienceKyotoJapan
  2. 2.Division of Metabolism, Nephrology and RheumatologyJapanese Red Cross Kyoto Daini HospitalKyotoJapan
  3. 3.Department of Anatomy and NeurobiologyKyoto Prefectural University of MedicineKyotoJapan

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