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GLP-1 Receptor Agonists in Obesity and Type 2 Diabetes: A Narrative Review of Clinical Effectiveness, Safety, And Future Directions
Subject area: Biological & Medical Sciences · Area of research: Pharmacy
DOI: https://doi.org/10.64388/IREV8I6-1719510
Abstract
Background: Since they were first discovered as a glucose-lowering drug, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have developed into drugs with significant impacts on weight loss and cardiorenal protection in the treatment of type 2 diabetes mellitus. This huge increase in evidence coupled with the emergence of dual incretin agonism calls for a comprehensive integration. Objective: To assess the clinical efficacy of the GLP-1 RAs and the dual GLP-1 and GIP receptor agonist tirzepatide in the domains of glycaemic, weight and cardiorenal clinical outcomes in type 2 diabetes and obesity; to review their safety profile; and to suggest future directions for the use of the class. Methods: This review is written in the fashion of a narrative review, combining data from 20 landmark and key { }randomized controlled trials (RCTs) and meta-analyses from cardiovascular outcome trials (CVOTs), weight-management trials and head-to-head comparisons published from 2016 to 2023. Results: All GLP-1 RAs have a proven ability to lower HbA1c consistently and to decrease body weight, and some agents have been proven to decrease major adverse cardiovascular events and renal outcomes in type 2 diabetes. Semaglutide is associated with reduction in cardiovascular events in obesity without diabetes and tirzepatide has had unprecedented reduction in glycaemic and weight status in head-to-head and placebo-controlled trials. The gastrointestinal side effect profile prevails, and low intrinsic hypoglycaemia risk. Conclusion: GLP-1 RAs and dual incretin agonists have come into a new role in the management of type 2 diabetes and obesity providing metabolic and cardiorenal benefit. New product development activities involve oral formulations, new multi-agonists and new indications that are not related to glycaemia and weight.
Keywords
GLP-1 Receptor Agonists, Type 2 Diabetes, Obesity, Tirzepatide, Semaglutide, Cardiovascular Outcomes, Narrative Review
How to cite this paper
@article{1719510,
author = {Harry S Patel},
title = {GLP-1 Receptor Agonists in Obesity and Type 2 Diabetes: A Narrative Review of Clinical Effectiveness, Safety, And Future Directions},
journal = {Iconic Research And Engineering Journals},
year = {2024},
volume = {8},
number = {6},
pages = {1315-1328},
issn = {2456-8880},
url = {https://www.irejournals.com/formatedpaper/1719510.pdf},
abstract = {Background: Since they were first discovered as a glucose-lowering drug, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have developed into drugs with significant impacts on weight loss and cardiorenal protection in the treatment of type 2 diabetes mellitus. This huge increase in evidence coupled with the emergence of dual incretin agonism calls for a comprehensive integration.
Objective: To assess the clinical efficacy of the GLP-1 RAs and the dual GLP-1 and GIP receptor agonist tirzepatide in the domains of glycaemic, weight and cardiorenal clinical outcomes in type 2 diabetes and obesity; to review their safety profile; and to suggest future directions for the use of the class.
Methods: This review is written in the fashion of a narrative review, combining data from 20 landmark and key { }randomized controlled trials (RCTs) and meta-analyses from cardiovascular outcome trials (CVOTs), weight-management trials and head-to-head comparisons published from 2016 to 2023.
Results: All GLP-1 RAs have a proven ability to lower HbA1c consistently and to decrease body weight, and some agents have been proven to decrease major adverse cardiovascular events and renal outcomes in type 2 diabetes. Semaglutide is associated with reduction in cardiovascular events in obesity without diabetes and tirzepatide has had unprecedented reduction in glycaemic and weight status in head-to-head and placebo-controlled trials. The gastrointestinal side effect profile prevails, and low intrinsic hypoglycaemia risk.
Conclusion: GLP-1 RAs and dual incretin agonists have come into a new role in the management of type 2 diabetes and obesity providing metabolic and cardiorenal benefit. New product development activities involve oral formulations, new multi-agonists and new indications that are not related to glycaemia and weight. },
keywords = {GLP-1 Receptor Agonists, Type 2 Diabetes, Obesity, Tirzepatide, Semaglutide, Cardiovascular Outcomes, Narrative Review},
month = {December},
doi = {https://doi.org/10.64388/IREV8I6-1719510}
}