Researchers highlight the unprecedented success of GLP-1-based multi-receptor drugs in achieving substantial weight loss and improved health outcomes, potentially replacing bariatric surgery for obesity treatment.
By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Jul 28 2024 In a recent review published in the journal Cell , researchers collate and elucidate recent research and clinical trials highlighting the mechanistic underpinnings and beneficial outcomes of glucagon-like peptide-1 -based polyagonists.
Background Obesity, clinically defined as a body mass index > 35 kg/m2, is characterized by excessive body fat and presents one of the most pressing public health concerns of the world today. The World Health Organization estimates a current global prevalence of 16% in adults aged 18 and over. In recent decades, the incidence of the condition has been rising at alarming rates – from 4% to 13% of the global population between 1975 and 2014.
The role of glucagon and incretin hormones in weight management As early as 1906, clinicians observed that blood glucose uptake is significantly higher when glucose is absorbed through the gut than intravenous infusion. This suggested the presence and potency of intestine-secreted insulinotropic hormones . Still, it was not until 1973 and 1987 that glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 were discovered and characterized.
Research and development of GLP-1R agonists – single receptor interventions Despite its substantial in vitro and in vivo benefits, native GLP-1’s use in pharmacological interventions was hampered by its extremely limited half-life , with studies estimating that even in sustained administration, only 10% of active GLP-1 enters general circulation, and even less reaches its target organ – the brain.
“Multiple gut-hormone combinations have been explored preclinically, with an appreciable number having advanced to clinical studies, with unimolecular peptides possessing varying degrees of GLP-1R, GIPR, and GCGR activity constituting the clinically most matured set of drug candidates.”
GLP-1 Surgery Weight Loss Blood Body Mass Index Cell Diabetes Drugs Fatty Liver Glucagon Glucagon-Like Peptide-1 Glucose Glycemia Hormone In Vivo Insulin Kidney Kidney Disease Liver Obesity Public Health Receptor Research Type 2 Diabetes
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