title: Therapeutic potential of coagonists of glucagon and GLP-1.
abstract: Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors reduces body weight without inducing hyperglycemia. In addition, coagonists have demonstrated lipid lowering property, which was independent of their anorectic effect. Similarly, GLP-1 modulates cardiovascular function which is favorable for treatment of myocardial injury, cardiac dysfunction, cardiac arrhythmias, endothelial dysfunction, and blood pressure, while glucagon has a positive impact on heart rate, cardiac output, ventricular contraction and enhances cardiac performance in animals and humans. Hence, researchers focused on combining these attributes of GLP-1 and glucagon in a single molecule, which was termed as a coagonist. Oxyntomodulin is the naturally occurring coagonist of GLP-1 and glucagon. This review focusses on the coagonists under clinical development discussing activities affecting cardiovascular functions, lipid modulation, direct effect on cardiac functions or other related functions. A comparative analysis of the in vitro and in vivo properties of GLP-1, glucagon and the coagonists is also carried out. This review discusses potential of GLP-1 and glucagon coagonists in treatment of cardiovascular and hemodynamic diseases with attention to GLP-1 or glucagon receptor specific properties as well as the interaction between other therapies.
authors.forename: Vishal J
authors.initials: VJ
authors.lastname: Patel
authors.forename: Amit A
authors.initials: AA
authors.lastname: Joharapurkar
authors.forename: Samadhan G
authors.initials: SG
authors.lastname: Kshirsagar
authors.forename: Kartikkumar N
authors.initials: KN
authors.lastname: Patel
authors.forename: Gaurang B
authors.initials: GB
authors.lastname: Shah
authors.affiliation: Department of Pharmacology and Toxicology, Zydus Research Centre, Sarkhej Bavla NH No. 8A, Moraiya, Ahmedabad 382210, India. amitjoharapurkar@zyduscadila.com.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism*; D005934:Glucagon / Q000819:agonists*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D053772:Oxyntomodulin / Q000627:therapeutic use*
chemical_list: D053772:Oxyntomodulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon