title: 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.
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.
authors.affiliation: 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.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: 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.
authors.forename: Muhei
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Metabolism, Nephrology and Rheumatology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okada
authors.affiliation: 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.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Mistuhashi
authors.affiliation: 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.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kimura
authors.affiliation: 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.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kitagawa
authors.affiliation: 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.
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: 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.
authors.forename: Saori
authors.initials: S
authors.lastname: Majima
authors.affiliation: 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.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fukuda
authors.affiliation: 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.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamada
authors.affiliation: 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.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senmaru
authors.affiliation: 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.
authors.forename: Masahide
authors.initials: M
authors.lastname: Hamaguchi
authors.affiliation: 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.
authors.forename: Mai
authors.initials: M
authors.lastname: Asano
authors.affiliation: 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.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: 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.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Division of Metabolism, Nephrology and Rheumatology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
authors.forename: Goji
authors.initials: G
authors.lastname: Hasegawa
authors.affiliation: 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.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: 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. sayarinapm@hotmail.com.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Fukui
mesh_terms: D000818:Animals; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008687:Metformin / Q000008:administration & dosage*; D010865:Pilot Projects; D011924:Rats, Zucker
chemical_list: D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1; D008687:Metformin
keywords: Biguanides; Gastric emptying; Glucagon-like peptide-1 (GLP-1); Incretin; Metformin; Postprandial hyperglycemia; Type 2 diabetes