GLP-1 & Metabolic Hormones

Byetta · Bydureon

Exenatide is a GLP-1 receptor agonist derived from exendin-4, a peptide found in Gila monster saliva. The first GLP-1 RA approved for type 2 diabetes, it established the GLP-1 drug class. Extended-release formulations (Bydureon) allow once-weekly dosing. Emerging research explores repurposing for Parkinson's disease, where small trials show motor improvement, and Alzheimer's disease neuroprotection.

Glucose-dependent Insulinotropic Polypeptide · Gastric Inhibitory Polypeptide

GIP is a 42-amino-acid incretin hormone secreted by duodenal K-cells in response to fat and carbohydrate ingestion. Like GLP-1, it enhances glucose-dependent insulin secretion. Unlike GLP-1, it also promotes insulin secretion during hypoglycemia, protects β-cells, and at high doses may stimulate glucagon in a glucose-independent manner. The GIP receptor's role in energy homeostasis underlies the efficacy of dual GIP/GLP-1 agonists like tirzepatide.

Glucagon-like Peptide-1 · GLP-1(7-37)

GLP-1 is an endogenous incretin hormone secreted by intestinal L-cells in response to nutrient ingestion. It enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and signals satiety to the hypothalamus. Native GLP-1 has a half-life of only 1–2 minutes due to DPP-4 degradation, which drove the development of DPP-4-resistant analogs (semaglutide, liraglutide, exenatide) that are now major drug classes.

GCG

Glucagon is a 29-amino-acid pancreatic alpha-cell hormone and physiological counter-regulator to insulin. It raises blood glucose through hepatic glycogenolysis and gluconeogenesis and is also lipolytic and thermogenic at supraphysiological doses. FDA-approved for hypoglycemia rescue and GI relaxation, it is now a major drug design target as a component of dual (GLP-1/glucagon) and triple agonists for obesity and NASH treatment.

Victoza · Saxenda

Liraglutide is a once-daily GLP-1 receptor agonist approved for type 2 diabetes (Victoza) and obesity (Saxenda). It achieves fatty acid attachment to albumin for extended half-life, enabling daily dosing. The LEADER trial established significant cardiovascular mortality benefit in high-risk patients, and research continues into neuroprotective and anti-inflammatory properties beyond metabolic indications.

Sandostatin · SMS 201-995

Octreotide is a synthetic 8-amino-acid somatostatin analog with a much longer half-life than native somatostatin. FDA-approved for acromegaly, carcinoid syndrome, VIPomas, and variceal bleeding, it is also used off-label for Cushing's disease, thyroid cancer, and refractory diarrhea. Long-acting release (LAR) formulations allow monthly dosing. It is among the most clinically important peptide drugs in endocrinology.

Symlin · synthetic amylin

Pramlintide is a synthetic analog of amylin, a peptide co-secreted with insulin from pancreatic β-cells. Approved as adjunct therapy to insulin in type 1 and type 2 diabetes, it slows gastric emptying, suppresses postprandial glucagon, and promotes satiety. It is the only amylinomimetic approved for clinical use and is studied for its complementary role to insulin in postprandial glucose control.

LY3437943

Retatrutide is a triple agonist targeting GIP, GLP-1, and glucagon receptors simultaneously. Phase 2 trials demonstrated up to 24.2% body weight reduction — the highest achieved by any pharmacotherapy to date. The addition of glucagon agonism enhances energy expenditure and lipid metabolism beyond dual incretin agonists. Phase 3 trials are underway for obesity and NASH.

Ozempic · Wegovy

Semaglutide is a long-acting GLP-1 receptor agonist approved for type 2 diabetes (Ozempic, Rybelsus) and obesity (Wegovy). By mimicking the incretin hormone GLP-1, it enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via central hypothalamic pathways. Landmark trials demonstrate up to 15–17% body weight reduction and significant cardiovascular mortality benefit.

SRIF · Somatotropin Release-Inhibiting Factor

Somatostatin is a 14-amino-acid cyclic peptide and the primary endogenous inhibitor of growth hormone secretion. It also inhibits insulin, glucagon, gastrin, cholecystokinin, and secretin release, slows GI motility, and reduces splanchnic blood flow. Its short half-life drove the development of longer-acting analogs (octreotide, lanreotide) used clinically for acromegaly, neuroendocrine tumors, and GI bleeding.

Mounjaro · Zepbound

Tirzepatide is the first dual GIP/GLP-1 receptor agonist, approved for type 2 diabetes (Mounjaro) and obesity (Zepbound). By co-activating both incretin receptors, it achieves superior glycemic control and weight reduction compared to GLP-1 monotherapy — SURMOUNT trials showed up to 22.5% body weight reduction. It represents a new class of metabolic peptide therapeutics with broad cardiovascular and metabolic benefits.