| アブストラクト | Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are clinically used to control hyperglycemia and body weight in patients with type 2 diabetes mellitus and obesity. Despite their efficacy, GLP-1 RAs frequently induce nausea and vomiting as adverse effects, which are prominent factors for non-adherence to GLP-1 RAs. Therefore, new prophylaxes and treatments for GLP-1 RA-induced nausea are urgently needed. Here, we explored the U. S. Food and Drug Administration (FDA) Adverse Event Reporting System database to determine the effective drug combinations mitigating GLP-1 RA-induced nausea and vomiting in real-world settings. We further investigated the effects of the identified drugs on GLP-1 RA-induced pica behavior, a behavioral index of nausea in mice. Analysis of the FDA Adverse Event Reporting System revealed that therapeutics, including gabapentin and acetaminophen, significantly lowered the occurrence of nausea-related events in GLP-1 RA-treated patients. In mice, we confirmed that exenatide, a GLP-1 RA, significantly increased the pica behavior in a dose-dependent manner, without affecting the food intake. Finally, we found that co-treatment with gabapentin significantly decreased the pica behavior induced by exenatide. These results demonstrate the therapeutic efficacy of gabapentin against nausea and vomiting in patients administered GLP-1 RAs. |
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| 投稿者 | Shibui, Norihiro; Suzuki, Takahide; Yamamoto, Hiroki; Shirakawa, Hisashi; Kaneko, Shuji; Yamamoto, Kouichi; Nagayasu, Kazuki |
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| 組織名 | Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences,;Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.;Laboratory of Clinical Evidence-based Drug Discovery, Graduate School of;Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka;812-8582, Japan.;Department of Radiological Sciences, Faculty of Health Sciences, Morinomiya;University of Medical Sciences, 1-26-16 Nanko-Kita, Suminoe-ku, Osaka 559-8611,;Japan.;Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical;Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.;Project for Neural Networks, Graduate School of Pharmaceutical Sciences, Osaka;University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. |
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