Semaglutide (trade name Ozempic) is a pharmaceutical drug in development by a Danish company Novo Nordisk for the treatment of type 2 diabetes. Semaglutide is a once-daily glucagon-like peptide-1 analog that differs to others by the presence of an acyl group with a steric diacid at Lys26 and a large synthetic spacer and modified by the presence of a α-aminobutyric acid in position 8 which gives stability against the dipeptidylpeptidase-4. Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Abaloparatide (brand name Tymlos) is a human parathyroid hormone related peptide [PTHrP(1-34)] analog indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Abaloparatide is a PTHrP(1-34) analog which acts as an agonist at the PTH1 receptor (PTH1R). This results in activation of the cAMP signaling pathway in target cells. In rats and monkeys, abaloparatide had an anabolic effect on bone, demonstrated by increases in BMD and bone mineral content (BMC) that correlated with increases in bone strength at vertebral and/or nonvertebral sites. Abaloparatide was approved in April 28, 2017 by the FDA (as Tymlos) for the treatment of postmenopausal women with osteoporosis at high risk for fracture.

Lixisenatide (trade name Adlyxin) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Parathyroid hormone (PTH) is an 84-amino acid peptide that regulates the function of osteoblasts and osteocytes and is secreted by the parathyroid gland in response to changes in the concentration of extracellular calcium. Parathyroid hormone is approved under the brand name NATPARA as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. It is also available for treatment of postmenopausal osteoporosis in many European countries. Parathyroid hormone is an activator of parathyroid hormone 2 receptor. In addition, was shown, that downregulation of Notch in osteoblasts and osteocytes may represent a mechanism contributing to the anabolic effects of parathyroid hormone in bone.

Linaclotide (marketed under the trade name Linzess and Constella) is a peptide agonist of the guanylate cyclase 2C (GC-C). Once linaclotide and its active metabolite binds to GC-C, it has local effect on the luminal surface of the intestinal epithelium. Activation of GC-C by linaclotide results in the intra- and extracellular increase of cyclic guanosine monophosphate concentrations (cGMP). This elevation of cGMP levels stimulates the secretion of chloride and bicarbonate into the intestinal lumen via activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. The metabolite of linaclotide MM-419447 (CCEYCCNPACTGC) contributes to the pharmacologic effects of linaclotide. Ultimately, linaclotide helps patients with IBS (especially with constipation) as GI transit is accelerated and the release of intestinal fluid is increased. In animal models, a decrease in visceral pain after administration of linaclotide may be observed. A decrease in the activity of pain-sensing nerves occurs as a result of an increase in extracellular cGMP. It was approved by the FDA in August 2012 for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) in adults.

Teduglutide is a glucagon-like peptide-2 (GLP-2) analogue. It is made up of 33 amino acids and is manufactured using a strain of Escherichia coli modified by recombinant DNA technology. Teduglutide differs from GLP-2 by one amino acid (alanine is substituted by glycine). The significance of this substitution is that teduglutide is longer acting than endogenous GLP-2 as it is more resistant to proteolysis from dipeptidyl peptidase-4. GLP-2 is known to increase intestinal and portal blood flow, and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF). FDA approved on December 21, 2012. In Europe it has been granted orphan drug status and is marketed under the brand Revestive by Nycomed. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion.

Lanreotide is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analog of somatostatin. It is available in several countries, including the United Kingdom, Australia and Canada, and was approved for sale in the United States by the Food and Drug Administration on August 30, 2007. Lanreotide was developed in the lab of Dr. David H. Coy, School of Medicine. Dr. Coy serves as Director of the Peptide Laboratory. Lanreotide (as lanreotide acetate) is manufactured by Ipsen, and marketed under the trade name Somatuline. The mechanism of action of lanreotide is believed to be similar to that of natural somatostatin. Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR1, 3, and 4. Activity at human SSTR 2 and 5 is the primary mechanism believed responsible for GH inhibition. Like somatostatin, lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine and paracrine functions. Lanreotide inhibits the basal secretion of motilin, gastric inhibitory peptide and pancreatic polypeptide, but has no significant effect on the secretion of secretin. Lanreotide inhibits postprandial secretion of pancreatic polypeptide, gastrin and cholecystokinin (CCK). In healthy subjects, lanreotide produces a reduction and a delay in post-prandial insulin secretion, resulting in transient, mild glucose intolerance.

Exenatide (exendin-4) is sold under the brand name BYETTA to improve glycemic control in people with type 2 diabetes mellitus. Exenatide is a glucagon-like peptide 1 (GLP-1) receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals but does not interfere with glucagon release in response to hypoglycemia.

Insulin detemir, a long-acting human insulin analog, is sold under the brand name LEVEMIR to improve glycemic control in adults and children with diabetes mellitus. Insulin detemir binds to the insulin receptor. Receptor-bound insulin lowers blood glucose by facilitating cellular uptake of glucose into skeletal muscle and adipose tissue and by inhibiting the output of glucose from the liver. The primary activity of insulin detemir is the regulation of glucose metabolism. Insulin detemir crosses the BBB and reduces food intake, it improves weight management by an enhanced and prolonged centrally mediated reduction of energy intake.

Triptorelin is a synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). It works by decreasing the production of certain hormones, which reduces testosterone levels in the body. Animal studies comparing triptorelin to native GnRH found that triptorelin had 13 fold higher releasing activity for luteinizing hormone, and 21-fold higher releasing activity for follicle-stimulating hormone. Triptorelin is indicated for the palliative treatment of advanced prostate cancer.