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Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and consequently energy intake, increasing energy expenditure, redirecting nutrients from adipose to lean tissue, or interfering with the absorption of calories.
Enteroglucagon is a peptide hormone derived from preproglucagon. It is a gastrointestinal hormone, secreted from mucosal cells primarily of the colon and terminal ileum. It consists of 37 amino acids. Enteroglucagon is released when fats and glucose are present in the small intestine; which decrease the motility to allow sufficient time for these nutrients to be absorbed.
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.
Liraglutide, sold under the brand names Victoza and Saxenda among others, is an anti-diabetic medication used to treat type 2 diabetes, and chronic obesity. It is a second-line therapy for diabetes following first-line therapy with metformin. Its effects on long-term health outcomes like heart disease and life expectancy are unclear. It is given by injection under the skin.
Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.
Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is a once-weekly injection.
Daniel Joshua Drucker is a Canadian endocrinologist. A Fellow of the Royal Society, he is a professor of medicine at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto. He is known for his research into intestinal hormones and their use in the treatment of diabetes, obesity, and other metabolic diseases, as well as intestinal failure.
Cotadutide is an experimental drug for the treatment of type 2 diabetes mellitus. It lowers blood glucose levels by mimicking the human hormones glucagon-like peptide 1 and glucagon, which play a role in blood sugar regulation. The drug is a peptide that is injected under the skin.
Tirzepatide, sold under the brand name Mounjaro among others, is an antidiabetic medication used for the treatment of type 2 diabetes and for weight loss. Tirzepatide is administered via subcutaneous injections.
Orforglipron (LY-3502970) is a non-peptide glucagon-like peptide-1 receptor agonist developed as a weight loss drug by Eli Lilly and Company. It is easier to produce than GLP-1 agonists on the market in 2023 and is expected to be cheaper.
MariTide, also known as maridebart cafraglutide, is an investigational drug developed by Amgen for the treatment of obesity. It is an agonist of the GLP-1 receptor and an antagonist of the GIPR. In a preliminary trial, AMG 133 resulted in a 14.5 percent weight loss after 12 weeks at the highest dose tested.
NNC9204-1706 or NN9423 is a GLP-1/GIP/glucagon receptor triple agonist developed by Novo Nordisk. It was evaluated in a clinical trial; adverse effects such as "dose-dependent increases in heart rate and reductions in reticulocyte count, increases in markers of inflammation and hepatic disturbances, and impaired glucose tolerance at the highest dosages" meant that the drug was declared to have an inadequate safety profile and discontinued.
Mazdutide is a dual agonist of the GLP-1 receptor and glucagon receptor. It is an analog of oxyntomodulin (OXM). The drug is developed by Eli Lilly and is currently in a Phase II study.
Glucagon receptor agonists are a class of drugs under development for the treatment of obesity, non-alcoholic fatty liver disease, and congenital hyperinsulinism.
GLP1 poly-agonist peptides are a class of drugs that activate multiple peptide hormone receptors including the glucagon-like peptide-1 (GLP-1) receptor. These drugs are developed for the same indications as GLP-1 receptor agonists—especially obesity, type 2 diabetes, and non-alcoholic fatty liver disease. They are expected to provide superior efficacy with fewer adverse effects compared to GLP-1 mono-agonists, which are dose-limited by gastrointestinal disturbances. The effectiveness of multi-receptor agonists could possibly equal or exceed that of bariatric surgery. The first such drug to receive approval is tirzepatide, a dual agonist of GLP-1 and GIP receptors.
Efinopegdutide (MK-6024) is a dual agonist of the glucagon and GLP-1 receptors. It is being developed by Merck for non-alcoholic fatty liver disease. It was also developed for type 2 diabetes and obesity but these indications were discontinued.
HRS9531 is an experimental GLP-1 and GIPR dual agonist developed by Jiangsu Hengrui.
Survodutide is an experimental peptide that works as a dual glucagon/GLP-1 receptor agonist. Unlike other dual GLP-1/glucagon dual agonists, it is an glucagon analog rather than an analog of oxyntomodulin. It is developed by Boehringer Ingelheim as a weight loss drug.
VK2735 is a dual agonist of the GLP-1 receptor and GIP receptor, with a similar mechanism of action as tirzepatide, which acts on the same receptors. It is injectable and is being developed by Viking Therapeutics.
References
- ↑ Beaney, Abigail (30 June 2023). "Obesity: Six trials to watch over the next 12 months". Clinical Trials Arena. Retrieved 5 December 2023.
- ↑ Bailey, Clifford J.; Flatt, Peter R.; Conlon, J. Michael (March 2023). "An update on peptide-based therapies for type 2 diabetes and obesity". Peptides. 161: 170939. doi: 10.1016/j.peptides.2023.170939 .
- ↑ Plutzky, Jorge; Harris, M. Scott S; Alonso, Cristina; Suschak, John; Noor, Mustafa; Ortiz, Pablo; Georges, Bertrand; Rader, Daniel J; Roberts, Scot S; Browne, Sarah K (8 November 2022). "Abstract 13440: Effect of Pemvidutide (ALT-801), a Novel GLP-1/Glucagon Dual Receptor Agonist, on Pathogenic Lipid Mediators". Circulation. 146 (Suppl_1). doi:10.1161/circ.146.suppl_1.13440.
- ↑ Klein, Samuel; Nestor, John J.; Harris, M. Scott; Suyundikov, Anvar; Casper, Rob; Steele, Staci M.; Payne, Jacques D.; Krishnan, Vyjayanthi; Roberts, M. Scot; Browne, Sarah K. (1 June 2022). "334-OR: Pemvidutide (ALT-801) , a Balanced (1:1) GLP-1/Glucagon Dual Receptor Agonist, Induces Rapid and Marked Weight Loss without the Need for Dose Titration in People with Overweight/Obesity". Diabetes. 71 (Supplement_1). doi:10.2337/db22-334-OR.
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