Article
Pharmacology & Pharmacy
Songfeng Zhao, Zhiming Yan, Yue Du, Zeyun Li, Chunli Tang, Lin Jing, Lidan Sun, Qimeng Yang, Xueling Tang, Yongliang Yuan, Jing Han, Neng Jiang
Summary: This study demonstrates the therapeutic potential of dual agonists targeting GLP-1/glucagon and GLP-1/CCK2 receptors in the treatment of obesity and diabetes. The newly developed peptide, xGLP-1/GCG/gastrin, showed significant anti-diabetes and anti-obesity effects in both in vitro and in vivo experiments.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jing Xu, Shuang Wang, Han Wu, De Chen, Jing Han, Qisi Lin
Summary: Novel dual agonists that target both the GLP-1 and Y2 receptors have the potential to be more effective in treating obesity and diabetes than current GLP-1 receptor agonists. In this study, researchers optimized the structure of a previously identified dual agonist and identified a lead peptide, xGLP/PYY-6, that showed improved stability and comparable potency to existing drugs. Animal experiments demonstrated that xGLP/PYY-6 had comparable hypoglycemic effects and better appetite suppression compared to semaglutide, and also exhibited significant metabolic benefits in regulating lipid levels and reversing fatty liver effects.
Article
Endocrinology & Metabolism
Arvid Jungnik, Jorge Arrubla Martinez, Leona Plum-Moerschel, Christoph Kapitza, Daniela Lamers, Claus Thamer, Corinna Schoelch, Michael Desch, Anita M. Hennige
Summary: This study reports on two phase I trials evaluating the subcutaneous GLP-1R/GCGR dual agonist BI 456906 versus placebo in healthy volunteers and overweight/obese individuals. The results demonstrate that BI 456906 significantly reduces body weight, with a 13.8% decrease at week 16.
DIABETES OBESITY & METABOLISM
(2023)
Article
Integrative & Complementary Medicine
Li Qiang, Yang Qimeng, Han Jing, Liu Xiaohan, Fu Junjie, Yin Jian
Summary: Peptide dual agonists that target both GLP-1R and GCGR receptors have emerged as potential therapeutics for treating type 2 diabetes with obesity. O-GlcNAcylation was shown to improve the stability of a dual GLP-1R/GCGR agonist, leading to significant weight loss and hypoglycemic effects.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Article
Chemistry, Medicinal
Neng Jiang, Lin Jing, Qing Li, Sibiao Su, Qimeng Yang, Feng Zhou, Xinyu Chen, Jing Han, Chunli Tang, Weizhong Tang
Summary: Dual activation of the glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) can potentially lead to effective therapy for diabetes and obesity. Novel peptides with dual activity on GLP-1R and GCGR were discovered through rational design, with xGLP/GCG-15 showing promising anti-obesity and anti-diabetic effects in preclinical studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Yumie Takeshita, Yuki Kita, Takeo Tanaka, Hisanori Goto, Yujiro Nakano, Chisato Teramura, Yasufumi Enyama, Toshinari Takamura
Summary: The study found that GLP-1 receptor agonists can effectively lower blood glucose levels in diabetic patients, even without prior glycemic control. However, for insulinopenic type 2 diabetes patients, prior glycemic control with insulin may help overcome glucose toxicity-induced GLP-1 resistance.
JOURNAL OF DIABETES INVESTIGATION
(2022)
Article
Endocrinology & Metabolism
Tina Zimmermann, Leo Thomas, Tamara Baader-Pagler, Peter Haebel, Eric Simon, Wolfgang Reindl, Besnik Bajrami, Wolfgang Rist, Ingo Uphues, Daniel J. Drucker, Holger Klein, Rakesh Santhanam, Dieter Hamprecht, Heike Neubauer, Robert Augustin
Summary: Obesity and its associated comorbidities require effective pharmaceutical interventions. BI 456906 is a dual agonist that reduces bodyweight by increasing energy expenditure and decreasing food intake.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Sora Q. Kim, Jeonghoon Kim, Mulim Choi, Young Kim, Shin Kim, Kee-Hong Kim
Summary: The combination of semaglutide and avasimibe showed the best weight reduction effects in obese mice, leading to lower body weight, plasma glucose, and leptin levels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Wen-Hsuan Tsai, Fung-Chang Sung, Lu-Ting Chiu, Ying-Hsiu Shih, Ming-Chieh Tsai, Shu- Wu
Summary: Patients with diabetes mellitus receiving GLP1-RA therapy have a greater reduction in the risk of anxiety than that of depression. The treatment effectiveness is significant for women and patients taking GLP1-RA for longer than 180 days. Dulaglutide could significantly decrease risks of both anxiety and depression.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Changliang Zhu, Hailiang Li, Xuerui Kong, Yezhong Wang, Tao Sun, Feng Wang
Summary: This article reviews the potential and mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of cocaine use disorder (CUD). Preclinical studies suggest that GLP-1RAs have promise in regulating cocaine-taking behavior and inhibiting inflammatory cytokines. However, further research is needed to address issues of clinical availability and specific mechanisms.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Hsuan-Wen Chou, Kai-Pi Cheng, An-Chi Lin, Hao-Chang Hung, Ching-Han Lin, Chih-Chen Wang, Hung-Tsung Wu, Horng-Yih Ou
Summary: GLP-1 RA has greater glycemic effects in insulin-treated patients compared to non-insulin-treated patients, with no significant differences in weight loss.
Article
Endocrinology & Metabolism
Ryosuke Ono, Kenichi Furihata, Yoshihiko Ichikawa, Yoshiomi Nakazuru, Arthur Bergman, Donal N. Gorman, Aditi R. Saxena
Summary: This study examined the safety, tolerability, pharmacokinetics and pharmacodynamics of danuglipron, a novel oral glucagon-like peptide-1 receptor agonist, in Japanese patients with type 2 diabetes mellitus. The results showed that danuglipron exhibited dose-proportional increases in plasma exposure and effectively reduced glycaemic parameters and body weight after 8 weeks of treatment, with a safety profile consistent with its mechanism of action.
DIABETES OBESITY & METABOLISM
(2023)
Article
Chemistry, Medicinal
Yongliang Yuan, Zhiming Yan, Qifang Lao, Neng Jiang, Shuangmin Wu, Qinpei Lu, Jing Han, Songfeng Zhao
Summary: The development of a unimolecular triple agonist peptide targeting GLP-1, glucagon, and Y2 receptors shows great potential as a novel anti-obesity and anti-diabetic agent. This peptide, 3b, demonstrated potent activity in reducing food intake without causing nausea and had better effects on lipid metabolism, body weight, and glycemic control compared to other agonist counterparts. Targeting GLP-1R, GCGR, and Y2R with a unimolecular triple agonist peptide offers a promising route for developing new treatments for obesity and T2DM.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Takayuki Masaki, Yoshinori Ozeki, Yuichi Yoshida, Mitsuhiro Okamoto, Shotaro Miyamoto, Koro Gotoh, Hirotaka Shibata
Summary: In obese type 2 diabetic patients, treatment with the GLP1-RA semaglutide resulted in improvements in body weight, HbA1c, and eating behavior, particularly in the sensation of hunger. The changes in hunger sensation were closely related to the improvement in HbA1c levels during treatment.
Article
Cardiac & Cardiovascular Systems
Xuefei Liu, Kaushik P. Patel, Hong Zheng
Summary: The study reveals that activation of renal sympathetic nerves contributes to the blunted diuretic and natriuretic effects of GLP-1 in HFD obese rats. The renal nerve-neprilysin-GLP-1 pathway is involved in renal dysfunction during obesity that leads to hypertension.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
