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.
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
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.
G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene.
Liraglutide, sold under the brand name Victoza 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.
Cinchonine is an alkaloid found in Cinchona officinalis. It is used in asymmetric synthesis in organic chemistry. It is a stereoisomer and pseudo-enantiomer of cinchonidine.
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.
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 loss.
Tirzepatide is an antidiabetic medication used for the treatment of type 2 diabetes and for weight loss. Tirzepatide is administered via subcutaneous injections. It is sold under the brand name Mounjaro for diabetes treatment, and Zepbound for weight loss and treatment of obstructive sleep apnea.
Danuglipron is a small-molecule GLP-1 agonist developed by Pfizer that, in an oral formulation, is under investigation as a therapy for diabetes mellitus. Initial results from a randomized controlled trial indicate that it reduced weight and improved diabetic control. The most commonly reported adverse events were nausea, diarrhea, and vomiting.
Orforglipron (LY-3502970) is an oral, non-peptide, small molecule glucagon-like peptide-1 receptor agonist developed as a weight loss drug by Eli Lilly and Company. It is easier to produce than current peptide GLP-1 agonists and is expected to be cheaper.
Retatrutide (LY-3437943) is an experimental drug for obesity developed by American pharmaceutical company Eli Lilly and Company. It is a triple glucagon hormone receptor agonist. It has been shown to achieve a more than 17.5% mean weight reduction in adults without diabetes but with obesity or preobesity (overweight) during a phase 2 trial.
Petrelintide is an amylin analogue dosed once weekly, developed by Zealand Pharma for the treatment of type 2 diabetes and obesity. Preclinical data suggests it may be more effective in combination with semaglutide. In June 2024 the company announced results for a Phase 1b trial, which found 8.6 percent weight loss over 16 weeks.
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.
HRS9531 is an experimental GLP-1 and GIPR dual agonist developed by Jiangsu Hengrui.
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.
Amycretin is a single molecule that operates as a GLP-1 receptor agonist and amylin receptor agonist. It is under development by Novo Nordisk as a weight loss drug; unlike some competitors, it can be delivered orally.
