Mechanism
Octreotide is a synthetic 8-amino-acid cyclic analog of native somatostatin (which is 14 amino acids). The truncation and modifications give it a half-life of approximately 90 minutes (subcutaneous), versus the 1–3 minute half-life of native somatostatin — long enough for therapeutic dosing.
It binds the somatostatin receptor family with selective affinity for SSTR2 and SSTR5 (high affinity), SSTR3 (moderate), and minimal binding to SSTR1 and SSTR4. The receptor selectivity is what gives it its therapeutic profile: SSTR2/5 binding suppresses GH, glucagon, and a range of GI hormones (gastrin, secretin, motilin, VIP, serotonin), which is the basis for its use in acromegaly, NETs, and dumping syndrome.
Long-acting formulations (Sandostatin LAR, lanreotide depot) use microsphere encapsulation to provide sustained release over ~28 days, allowing once-monthly dosing.
What the evidence shows
Acromegaly: Multiple decades of trials and post-marketing data. Octreotide LAR achieves biochemical control (normal IGF-1) in roughly 50–60% of patients with active acromegaly; remaining patients typically require pasireotide (a broader-spectrum somatostatin analog) or surgical/radiation management.
Neuroendocrine tumors: PROMID (2009) and CLARINET (2014, lanreotide) trials established somatostatin analogs as standard-of-care for symptom control and antiproliferative effect in well-differentiated NETs. Octreotide significantly delays time to tumor progression versus placebo.
Variceal bleeding: Multiple meta-analyses support octreotide infusion as an adjunct to endoscopic management of acute variceal hemorrhage, reducing rebleeding rate and transfusion requirements.
Refractory diarrhea, short bowel syndrome, dumping syndrome: Real evidence base, more limited; octreotide is the second-line option after dietary management fails.
The acromegaly and NET evidence is the strongest. The other indications are real but have smaller trials.
Dosing literature
Approved dosing varies dramatically by indication and formulation:
- Sandostatin (subcutaneous, immediate-release): 50–500 mcg, 2–3 times daily; titrate to response and tolerability
- Sandostatin LAR (intramuscular, monthly depot): 10–30 mg every 4 weeks; typical maintenance 20–30 mg
- IV infusion (variceal bleeding): 50 mcg bolus + 50 mcg/hour infusion for 2–5 days
Dosing requires a clinician — particularly because acromegaly patients often need biochemical monitoring (IGF-1) every 3 months to titrate the depot dose, and NET patients need imaging plus chromogranin A trends.
Risks and adverse events
Common:
- Steatorrhea, abdominal cramping, nausea — often improves over weeks
- Cholelithiasis (gallstones) — significant rate with long-term use; many patients eventually need cholecystectomy
- Hyperglycemia or hypoglycemia (the somatostatin pharmacology suppresses both insulin and glucagon; net effect varies)
- Injection site reactions
- Bradycardia, mild
Less common:
- Pancreatitis
- Hypothyroidism (rare; mostly with long-term high-dose use)
- Vitamin B12 deficiency with chronic use
- Worsening of glycemic control in patients with diabetes
The chronic-use safety profile is well-characterized — that’s the upside of decades of clinical experience.
Regulatory status
| Region | Status | Notes |
|---|---|---|
| United States | Approved (Sandostatin, Sandostatin LAR) | Multiple generics available. Oral octreotide (Mycapssa) FDA-approved 2020 for acromegaly maintenance therapy after response to injectable octreotide/lanreotide. |
| European Union | Approved (injectable); Mycapssa withdrawn | EMA marketing authorization for oral Mycapssa was withdrawn February 2025 — injectable octreotide remains approved unchanged. |
| United Kingdom | Approved | |
| Japan | Approved | |
| Most major markets | Approved |
Generic octreotide is widely available; Sandostatin LAR remains under brand-name distribution in most markets due to the depot formulation complexity.
Where to get it
Through a clinician (endocrinology, oncology, gastroenterology depending on indication) and a specialty pharmacy. The depot formulation requires specific reconstitution and intramuscular administration; not a self-administered drug for most use cases.
We have no fulfillment partner for octreotide. (See How we make money.)
References (selected)
- Rinke A et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors. J Clin Oncol
Quick Facts
| Also Known As | SMS 201-995, Sandostatin, Octreotide acetate |
|---|---|
| Sequence | D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (cyclic disulfide bond between Cys2 and Cys7) |
| Molecular Formula | C49H66N10O10S2 |
| Molecular Weight | 1019.2 Da |
| PubChem CID | 448601 |
Research Parameters
| Half-Life | ~1.7-1.9 hours (subcutaneous administration in humans) |
|---|---|
| Stability | Lyophilized powder is stable at recommended storage conditions. After reconstitution with sterile water, solutions are chemically stable for up to 2 weeks when stored at 2-8°C, but sterility considerations typically limit use to 24 hours unless prepared under aseptic conditions with a bacteriostatic agent. |
| Solubility | Recommended reconstitution in Sterile Water for Injection or Bacteriostatic Water for Injection (0.9% benzyl alcohol). |
| Storage (Lyophilized) | Store at 2-8°C, protected from light. For long-term storage, -20°C is recommended. |
| Storage (Reconstituted) | Store at 2-8°C and use within 24 hours unless prepared under aseptic conditions with a preservative, in which case stability may extend to 2 weeks. |
| Typical Research Dose | In human clinical research: 50-500 mcg SC TID. In animal research: 10-100 mcg/kg SC daily. |
| Cycle Parameters | In clinical research for chronic conditions: Continuous daily subcutaneous injections (e.g., 100 mcg TID) or monthly intramuscular depot injections. Animal study protocols vary widely based on model objectives. |
| Amino Acid Count | 11 |
Mechanism of Action
Octreotide exerts its effects primarily by mimicking the action of native somatostatin, binding with high affinity to G-protein coupled somatostatin receptors (SSTRs), particularly subtypes 2 and 5. Upon binding, it inhibits adenylate cyclase, reducing intracellular cyclic AMP (cAMP) levels. This leads to a broad spectrum of inhibitory effects on secretory processes and cell proliferation.
Inhibition of Hormone Secretion: Binding to SSTRs on target cells (e.g., pituitary somatotrophs, pancreatic islet cells, gastrointestinal endocrine cells) activates inwardly rectifying potassium channels and inhibits voltage-gated calcium channels. The resulting hyperpolarization and reduced calcium influx suppress the exocytotic release of hormones such as growth hormone, insulin, glucagon, gastrin, vasoactive intestinal peptide (VIP), and serotonin.
Antiproliferative Effects: Via SSTR-mediated activation of protein tyrosine phosphatases (PTPs), octreotide can dephosphorylate and inactivate growth factor receptor tyrosine kinases and downstream mitogenic signaling pathways like MAPK/ERK. This can lead to cell cycle arrest and induction of apoptosis in certain tumor cell types.
Inhibition of Angiogenesis: Octreotide can suppress the secretion of pro-angiogenic factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from tumor cells, thereby inhibiting the formation of new blood vessels that support tumor growth.
Modulation of Immune Response: Through SSTRs expressed on immune cells, octreotide can inhibit lymphocyte proliferation and the release of inflammatory cytokines, contributing to an anti-inflammatory effect.
Research Applications
Oncology Research: Octreotide is extensively studied for the management of neuroendocrine tumors (NETs), including carcinoid tumors and VIPomas. It effectively controls hormone-mediated symptoms like flushing and diarrhea (carcinoid syndrome) and exhibits direct antiproliferative effects on tumor cells, stabilizing disease progression.
Endocrinology Research: In acromegaly, octreotide research focuses on its ability to normalize elevated growth hormone and insulin-like growth factor 1 (IGF-1) levels, leading to reductions in soft tissue swelling and improved metabolic parameters. It is also investigated for its role in treating TSH-secreting pituitary adenomas and certain forms of congenital hyperinsulinism.
Gastroenterology Research: Studies explore its utility in reducing output from pancreatic fistulas and in the acute management of bleeding esophageal varices due to portal hypertension, where it reduces splanchnic blood flow by inhibiting the release of vasodilatory peptides.
Other Research Areas: Investigational uses include the treatment of diarrhea in AIDS patients, refractory chemotherapy-induced diarrhea, and certain forms of dumping syndrome, leveraging its potent inhibitory effect on gastrointestinal secretion and motility.
Safety & Side Effects
From extensive clinical and animal studies, common side effects are primarily gastrointestinal and include nausea, abdominal discomfort, diarrhea, steatorrhea, and flatulence, which often diminish with continued use. Injection site reactions (pain, redness) are also common. A significant long-term effect is the suppression of gallbladder contractility and bile secretion, leading to an increased incidence of gallstone (cholesterol gallstone) formation. Glucose metabolism can be affected due to inhibition of insulin and glucagon secretion, potentially causing hyperglycemia or, less commonly, hypoglycemia. Bradycardia and conduction abnormalities are rare but reported. In animal toxicology studies, findings are consistent with its pharmacologic action. Theoretical concerns exist regarding the potential for nutrient malabsorption with long-term use due to pancreatic exocrine inhibition.
Dosage Information
This information is derived from published clinical and preclinical research literature and is for research purposes only. In human clinical studies for conditions like acromegaly or NETs, typical subcutaneous doses range from 50 to 500 mcg administered two to three times daily. Long-acting depot formulations (e.g., Octreotide LAR) are administered intramuscularly at doses of 10 mg, 20 mg, or 30 mg every 4 weeks. In animal research, dosing varies significantly by species and model; for example, in rodent models of NETs, doses often range from 10 to 100 mcg/kg administered subcutaneously once or twice daily. The route is almost exclusively subcutaneous or intramuscular due to poor oral bioavailability. Duration of treatment in studies aligns with the experimental endpoint, from acute single-dose studies to chronic administration over many months.
References
Lamberts, S.W., van der Lely, A.J., de Herder, W.W., & Hofland, L.J. (1996). Octreotide. The New England Journal of Medicine, 334(4), 246-254.
Susini, C., & Buscail, L. (2006). Rationale for the use of somatostatin analogs as antitumor agents. Annals of Oncology, 17(12), 1733-1742.
Anthony, L., & Vinik, A.I. (2013). Evaluating the characteristics and the management of patients with neuroendocrine tumors receiving octreotide LAR during a 6-year period. Pancreas, 42(2), 240-246.
Melmed, S., et al. (2005). A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly. The Journal of Clinical Endocrinology & Metabolism, 90(7), 4405-4410.
Harris, A.G. (1994). Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. Gut, 35(3 Suppl), S1-4.
Oberg, K., et al. (2004). Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Annals of Oncology, 15(6), 966-973.
Moller, L.N., et al. (2003). Somatostatin receptors. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1616(1), 1-84.