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Drugs used in diabetes treat types of diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.
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.
Exenatide, sold under the brand name Byetta among others, is a medication used to treat type 2 diabetes. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin.
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.
G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene.
Albiglutide is a glucagon-like peptide-1 agonist drug marketed by GlaxoSmithKline (GSK) for treatment of type 2 diabetes. As of 2017 it is unclear if it affects a person's risk of death. In 2017 GSK announced Albiglutide's withdrawal from the worldwide market for economic reasons, and remaining stocks in the supply chain were effectively depleted by 2018.
Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs, or incretin mimetics, are a class of anorectic 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, which is released by the gut after eating.
Lixisenatide is a once-daily injectable GLP-1 receptor agonist for the treatment of type 2 diabetes.
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.
Semaglutide is an anti-diabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management. It is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1), modified with a side chain. It can be administered by subcutaneous injection or taken orally. It is sold by Novo Nordisk under the brand names Ozempic and Rybelsus for diabetes, and under the brand name Wegovy for weight management and weight loss.
Tirzepatide is an antidiabetic medication used for the treatment of type 2 diabetes and for weight loss. Tirzepatide is administered via subcutaneous injections. In the United States, it is sold under the brand name Mounjaro for diabetes treatment, and Zepbound for weight loss and treatment of obstructive sleep apnea.
Maridebart cafraglutide is an investigational drug developed by Amgen for the treatment of obesity. It is an agonist of the GLP-1 receptor (GLP-1R) and an antagonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR). Namely, MariTide consists of a monoclonal antibody against GIPR conjugated to two peptidic GLP-1R agonist molecules via amino acid linkers. In a preliminary trial, AMG 133 resulted in a 14.5 percent weight loss after 12 weeks at the highest dose tested.
Ecnoglutide (XW003) is a GLP-1 agonist being developed for the treatment of obesity and type 2 diabetes. In preclinical trials, "Ecnoglutide showed a favorable potency, pharmacokinetic, and tolerability profile, as well as a simplified manufacturing process" compared to other GLP-1 agonists.
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 multiple Phase III studies.
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.
Pemvidutide (ALT-801) is an experimental dual GLP-1/glucagon receptor agonist developed by Altimmune. The drug reduced LDL-C in a clinical trial and does not require dose titration as with GLP-1 mono agonists.
Dapiglutide is a dual GLP-1 and GLP-2 receptor agonist developed by Zealand Pharma.
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.
Lotte Bjerre Knudsen is a Danish scientist and university professor. She led the development of liraglutide and oversaw the development of semaglutide, two notable drugs approved for indications in the treatment of diabetes and obesity.
References
- ↑ Klein, Thomas; Augustin, Robert; Hennige, Anita M. (June 2023). "Perspectives in weight control in diabetes – BI 456906". Diabetes Research and Clinical Practice. 207: 110779. doi:10.1016/j.diabres.2023.110779. PMID 37330144. S2CID 259188902.
- ↑ Zimmermann, Tina; Thomas, Leo; Baader-Pagler, Tamara; Haebel, Peter; Simon, Eric; Reindl, Wolfgang; Bajrami, Besnik; Rist, Wolfgang; Uphues, Ingo; Drucker, Daniel J.; Klein, Holger; Santhanam, Rakesh; Hamprecht, Dieter; Neubauer, Heike; Augustin, Robert (December 2022). "BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy". Molecular Metabolism. 66: 101633. doi: 10.1016/j.molmet.2022.101633 . PMC 9679702 . PMID 36356832.
- ↑ Augustin, Robert; Thomas, Leo; Zimmermann, Tina; Simon, Eric; Rist, Wolfgang; Uphues, Ingo; Reindl, Wolfgang; Klein, Thomas; Neubauer, Heike (20 June 2023). "749-P: Selection of BI 456906 as a Dual GCGR/GLP-1R Agonist Based on In Vitro Potency and In Vivo Target Engagement Biomarkers". Diabetes. 72 (Supplement_1). doi:10.2337/db23-749-P. S2CID 259442329.