Emerging roles of oxyntomodulin-based glucagon-like peptide-1/glucagon co-agonist analogs in diabetes and obesity

Yao Zhihong; Wang Chen; Zhu Qianqian; Sun Lidan; Zhou Qiang; Han Jing; Wang Wenxi; Ruchika Bhawal

doi:10.1016/j.peptides.2023.170955

Emerging roles of oxyntomodulin-based glucagon-like peptide-1/glucagon co-agonist analogs in diabetes and obesity

Peptides. 2023 Apr:162:170955. doi: 10.1016/j.peptides.2023.170955. Epub 2023 Jan 18.

Authors

Yao Zhihong¹, Wang Chen², Zhu Qianqian², Sun Lidan³, Zhou Qiang⁴, Han Jing⁵, Wang Wenxi⁶, Ruchika Bhawal⁷

Affiliations

¹ Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, Jiaxing 314001, China; College of Pharmacy, Zhejiang University of Technology, Hangzhou 310000, China.
² Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, Jiaxing 314001, China.
³ Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, College of Medicine, Jiaxing University, Jiaxing 314001, China. Electronic address: [email protected].
⁴ The First Hospital of Jiaxing & The Affiliated Hospital of Jiaxing University, Jiaxing 314001, China. Electronic address: [email protected].
⁵ School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
⁶ The First Hospital of Jiaxing & The Affiliated Hospital of Jiaxing University, Jiaxing 314001, China; College of Pharmacy, Zhejiang University of Technology, Hangzhou 310000, China.
⁷ Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA.

PMID: 36669563
DOI: 10.1016/j.peptides.2023.170955

Abstract

Oxyntomodulin (OXM) is an endogenous peptide hormone secreted from the intestines following nutrient ingestion that activates both glucagon-like peptide-1 (GLP-1) and glucagon receptors. OXM is known to exert various effects, including improvement in glucose tolerance, promotion of energy expenditure, acceleration of liver lipolysis, inhibition of food intake, delay of gastric emptying, neuroprotection, and pain relief. The antidiabetic and antiobesity properties have led to the development of biologically active and enzymatically stable OXM-based analogs with proposed therapeutic promise for metabolic diseases. Structural modification of OXM was ongoing to enhance its potency and prolong half-life, and several GLP-1/glucagon dual receptor agonist-based therapies are being explored in clinical trials for the treatment of type 2 diabetes mellitus and its complications. In the present article, we provide a brief overview of the physiology of OXM, focusing on its structural-activity relationship and ongoing clinical development.

Keywords: Obesity; Oxyntomodulin; Structural modification; Type 2 diabetes.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2*
Glucagon / metabolism
Glucagon-Like Peptide 1 / metabolism
Glucagon-Like Peptide-1 Receptor / therapeutic use
Humans
Obesity / metabolism
Oxyntomodulin* / pharmacology

Substances

Oxyntomodulin
Glucagon-Like Peptide 1
Glucagon
Glucagon-Like Peptide-1 Receptor