Oral Semaglutide under Human Protocols and Doses Regulates Food Intake, Body Weight, and Glycemia in Diet-Induced Obese Mice

Author:

Rakhat Yermek12ORCID,Wang Lei12,Han Wanxin12,Rustemova Aktolkyn12,Kulzhanova Nazymgul12,Yamada Yuichiro3,Yabe Daisuke234ORCID,Seino Yutaka3,Yada Toshihiko124

Affiliation:

1. Division of Integrative Physiology, Kansai Electric Power Medical Research Institute, Kyoto 604-8436, Japan

2. Department of Diabetes, Endocrinology and Metabolism/Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan

3. Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Osaka 553-0003, Japan

4. Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu 501-1193, Japan

Abstract

The first oral form of the glucagon-like peptide-1 receptor agonist, oral semaglutide, has recently been launched and potently controls glycemia and body weight in subjects with type 2 diabetes. This drug carries the absorption enhancer and requires specific protocols of administration. The mechanism of action of oral semaglutide is not fully understood, for which an appropriate experimental model is required. This study explores the metabolic effects of oral semaglutide in mice under human protocols and doses. Oral semaglutide was bolus and once daily injected into high-fat diet-induced obese (DIO) mice under human protocols, followed by monitoring blood glucose, food intake, and body weight. Oral semaglutide 0.23 mg/kg, a comparable human dose (14 mg) in a small volume of water under human protocols rapidly decreased blood glucose and food intake and continuously reduced food intake and weight gain for 3 days in DIO mice. At 0.7 mg/kg (42 mg), this drug was somewhat more potent. Oral semaglutide with human protocols and doses rapidly reduces blood glucose and food intake and continuously suppresses feeding and weight in DIO mice. This study establishes mice as a model suitable for analyzing the mechanism of anti-obesity/diabetes actions of oral semaglutide.

Funder

Japan Society for the Promotion of Science

Kieikai Research Foundation

Japan Association for Diabetes Education and Care

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

Reference24 articles.

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2. MSc2 Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes;Gibbons;Diabetes Obes. Metab.,2021

3. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist;Buckley;Sci. Transl. Med.,2018

4. Oral semaglutide in type 2 diabetes;Anderson;J. Diabetes Complicat.,2020

5. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): A randomised, double-blind, phase 3A trial;Pratley;Lancet,2019

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