Glucagon Like Peptide Agonists as Therapy for Treatment of Cardiometabolic Diseases

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Authors: R B Singh, Mahmood Moshiri, Osama Elmarghi, Galal elkilany, Jan Fedacko, and Gushchina Yulia
Page Range: 145-156
Published in: World Heart Journal, 14#2 (2022)
ISSN: 1556-4002

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Table of Contents

ABSTRACT

The glucagon-like peptide-1 (GLP-1) has a broad pharmacological potential. After modification bio-chemically for enhanced potency and sustained action, GLP-1 receptor agonists are successfully used for the treatment of type-2 diabetes (T2DM) and cardiovascular diseases (CVDs). The beneficial effects of GLP-1 render it for the development of pharmacotherapies by developing long-acting analogues. At present, GLP-1 receptor agonists are injected twice daily (exenatide b.i.d.), once daily (lixisenatide and liraglutide), or once weekly (exenatide once weekly, dulaglutide, albiglutide, and semaglutide). A daily semaglutide oral tablet has been found to be as effective as once-weekly subcutaneous preparation. All GLP-1 receptor agonists have common mechanisms of action. There is an augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, deceleration of gastric emptying, and a decline in calorie intake and body weight. Exenatide b.i.d, and lixisenatide are short-acting with reduced effectiveness, whereas liraglutide, once-weekly, exenatide, dulaglutide, albiglutide, and semaglutide have more profound effects on overnight and fasting plasma glucose and HbA1c. GLP-1 receptor agonists are recommended as the first injectable glucose-lowering therapy for T2DM, even before insulin treatment, although they can be combined with (basal) insulins. More recently, semaglutide has been found to possess greater efficacy with respect to lowering plasma glucose as well as body weight. Since 2016, GLP-1 receptor agonists have been found to prevent CVDs, hence guidelines recommend treatment with these agents in patients with pre-existing atherosclerotic CVDs. Since sodium/glucose cotransporter-2 (SGLT-2) inhibitor therapy also reduces CVDs, in particular heart failure, the individual risk of ischemic or complications of heart failure should guide the choice of treatment. GLP-1 receptor agonists may also help prevent renal complications of T2DM. Novel indications for GLP-1 receptor agonists, such as T1DM, neurodegenerative diseases, and psoriasis, indicate that these agents have the potential for further development.

Keywords: Glucagon, GLP-1, insulin, diabetes, obesity; incretin, hormone

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