Somatostatin

SST, SRIF, growth hormone-inhibiting hormone (GHIH), somatotropin release-inhibiting factor; the native 14- and 28-amino-acid forms. Brand names for the native peptide used in hospital practice in some countries include Stilamin and Somatostatine †

Sexual health, hormones & signalling

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Native somatostatin is an approved hospital medicine in several European and Asian countries, given as a continuous intravenous infusion for acute gastrointestinal bleeding and related indications. It is not approved in the United States, United Kingdom or Australia, where the long-acting analogues are used instead. Nothing here describes a self-administered use; there is none.

Summary

Class: Naturally occurring cyclic peptide hormone with a disulphide bridge; two bioactive forms, somatostatin-14 and somatostatin-28, cleaved from a common precursor
Mechanism: Acts at five receptors (SSTR1–5) to inhibit secretion almost universally — growth hormone, TSH, insulin, glucagon, gastrin and pancreatic enzymes — and to reduce splanchnic blood flow
Routes studied: Continuous intravenous infusion (the only practical route — the half-life is too short for anything else)
Half-life: 1–3 minutes. This single fact explains everything about how the compound is used and why the analogues exist
Storage: Supplied as lyophilised powder with diluent for hospital pharmacy reconstitution; refrigerated, used promptly after reconstitution per the product label
Regulatory status: Approved in several EU member states and other countries for defined hospital indications; not approved in the US, UK or Australia. Analogues are approved far more widely

Doses are as reported in studies or by the community — never recommendations.

1What it is

Somatostatin was isolated in 1973 from sheep hypothalamus by Brazeau and Guillemin's group, as the factor that stops growth hormone release — hence the name. It turned out to be far more than a pituitary regulator. Somatostatin-producing cells (delta cells in the pancreatic islets, D cells in the stomach and gut, neurons throughout the brain and spinal cord) are everywhere, and the peptide's role is almost always the same: switch secretion off.

It is a universal inhibitor. It stops growth hormone and TSH from the pituitary, insulin and glucagon from the islets, gastrin and gastric acid from the stomach, enzymes from the exocrine pancreas, and it constricts the splanchnic circulation. In the brain, somatostatin-expressing interneurons are one of the major inhibitory populations in the cortex and hippocampus, and their loss is a feature of Alzheimer's disease and of depression neuropathology.

Its practical problem is the : one to three minutes. You cannot give it as an injection and expect anything to last. That is why native somatostatin survives clinically only as a continuous hospital infusion for acute bleeding, and why the entire therapeutic field runs on its long-acting analogues — octreotide (#124), lanreotide (#125) and pasireotide (#126), profiled separately. Community use: essentially none documented, and the minutes-long half-life makes it pharmacologically meaningless outside a drip.

2How it's thought to work

Binds SSTR1–SSTR5, all Gi-coupled: lowers cAMP, reduces calcium influx and activates potassium channels, which blocks hormone-containing vesicles from fusing.

Native somatostatin binds all five receptors with roughly comparable affinity — which is why it inhibits everything, and why the analogues were engineered for subtype selectivity (octreotide and lanreotide favour SSTR2 and SSTR5; pasireotide covers SSTR1, 2, 3 and 5).

Pituitary. SSTR2 and SSTR5 mediate GH and TSH suppression.

Islets. SSTR2 suppresses glucagon, SSTR5 suppresses insulin — the two effects partly cancel, which is why glucose effects are unpredictable rather than uniformly hyperglycaemic.

Splanchnic circulation. reduces portal and collateral blood flow and portal pressure, the mechanism exploited in variceal bleeding.

Gut. inhibits gastrin, acid, pancreatic enzyme and bile secretion, slows motility and reduces splanchnic absorption.

Antiproliferative and pro-apoptotic. effects via SSTR2 and SSTR3 in tumour cells — the basis of analogue therapy in neuroendocrine tumours and of somatostatin-receptor imaging and radioligand therapy.

CNS. somatostatin interneurons provide dendrite-targeting inhibition in cortex; this is a neuroscience story with no current therapeutic application.

The natural hormone itself, acting at five receptor subtypes. Activation suppresses release of growth hormone, insulin, glucagon and most gut hormones; its two-minute half-life is why analogues exist.Schematic — not to scale

3What the research shows

Acute variceal bleeding

Randomised trials and meta-analyses of somatostatin infusion in acute oesophageal variceal haemorrhage report improved control of bleeding compared with placebo, efficacy comparable to vasopressin or terlipressin with better tolerability, and benefit when combined with endoscopic therapy (Imperiale and Teres meta-analyses; Avgerinos and colleagues). This is the main licensed indication and the evidence is solid, though much of it predates current standards of care.

Graded A/B

Pancreatic surgery and fistula

Perioperative somatostatin or octreotide infusion reduces pancreatic fistula rates after pancreatic resection in several randomised trials and meta-analyses, though results vary by surgical technique and the clinical importance of the effect has been debated for decades.

Graded A (negative or inconclusive)

Acute pancreatitis

Despite a clean mechanistic rationale — switch off the exocrine pancreas — randomised trials of somatostatin and octreotide in acute pancreatitis have not shown convincing mortality or complication benefit, and it is not standard care.

Growth hormone suppression

The original pharmacology: somatostatin infusion reliably suppresses GH secretion in humans, which is foundational endocrinology and the basis for the analogues' use in acromegaly. Diagnostic and physiological rather than therapeutic in native form.

Secretory diarrhoea, chylothorax, enterocutaneous fistula

Infusion is used in some centres for high-output fistulas, chylous effusions and refractory secretory diarrhoea, largely on mechanism and case-series evidence, often with octreotide preferred for practical reasons.

Graded A (via analogues)

Neuroendocrine tumours

The hormone-control and antiproliferative benefits in neuroendocrine tumours were established with octreotide (PROMID) and lanreotide (CLARINET), not with the native peptide. Those trials are covered in profiles #124 and #125.

Graded C/D

CNS roles

Loss of somatostatin interneurons is documented in Alzheimer's disease and in major depression post-mortem studies, and somatostatin modulates amyloid-beta degradation via neprilysin in animal models. No therapeutic application; the peptide does not cross the blood–brain barrier.

4Reported side effects and interactions

Literature-reported

Infusion is generally well tolerated. Reported effects include nausea, abdominal cramping, flushing, bradycardia and transient disturbances of glucose in both directions — hyperglycaemia from glucagon and insulin suppression together, hypoglycaemia in some patients, which is why glucose monitoring accompanies the infusion. Abrupt discontinuation after prolonged infusion has been associated with rebound, so infusions are usually tapered or stopped alongside definitive treatment. Unlike the long-acting analogues, short infusions do not cause gallstones — that is a consequence of chronic SSTR2 blockade of gallbladder contraction and belongs to the analogue profiles.

Community-reported

None. Not in self-directed use.

Theoretical. Broad, non-selective inhibition of secretion means anything secretory is affected; the clinically relevant consequences in a hospital setting are glucose instability and bradycardia.

Interactions. Reduces absorption of some orally administered drugs by slowing gut transit and reducing splanchnic blood flow. Additive bradycardia with beta-blockers. Insulin and other glucose-lowering drug requirements commonly change during infusion. Somatostatin reduces the effect of GH, GHRH analogues and GH directly — mechanistically the exact opposite of the GH-axis compounds elsewhere on this site.

Markers researchers commonly monitor

These follow hospital infusion protocols:

Marker	Why it's watched
Blood glucose, frequently	the most important monitoring during infusion; somatostatin suppresses both insulin and glucagon and glucose can move either way. Patients with diabetes need particular attention.
Heart rate and rhythm	bradycardia is a recognised effect of infusion.
Haemoglobin, haematocrit and transfusion requirement	in the bleeding indication these are the outcome measures.
Blood pressure and signs of ongoing bleeding	clinical monitoring alongside endoscopic management.
Growth hormone and IGF-1	in endocrine research and diagnostic settings, where GH suppression is the measured effect.
Electrolytes and fluid balance	relevant in high-output fistula and secretory diarrhoea use.
Liver function and drain output	in the pancreatic surgery indication.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Native somatostatin is a hospital pharmacy product where it is licensed: powder with the supplied and given as a bolus followed by continuous intravenous infusion via pump, prepared fresh and protected per the label. Infusion rates are expressed in µg/hour. There is no regimen, no multi-dose vial practice and no outpatient use — the one-to-three-minute makes any intermittent route pointless, and that is the whole reason the analogues were developed. No calculator preset applies.

6Commonly studied alongside

Octreotide (#124), lanreotide (#125) and pasireotide (#126) — the long-acting analogues that replaced it for all chronic indications; terlipressin and vasopressin as alternatives in variceal bleeding; beta-blockers and endoscopic band ligation as the rest of the variceal-bleeding package; GHRH analogues and GH secretagogues as its mechanistic opposites; DOTATATE and DOTATOC radioligands, which exploit the same receptors for imaging and therapy.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Native somatostatin has never been marketed in the US; octreotide, lanreotide and pasireotide are used instead
European Union	Approved in several member states for acute gastrointestinal and variceal bleeding, pancreatic fistula prophylaxis and related hospital indications, under national authorisations rather than a central EMA one; availability and indications vary by country †
United Kingdom	Not licensed. Octreotide is used instead †
Australia	Not approved; octreotide and lanreotide are TGA-registered
South Africa	Native peptide not registered; octreotide availability should be confirmed with SAHPRA †
Sport	Somatostatin itself is not listed by WADA. Note the direction of effect: it suppresses growth hormone, so it has no performance rationale and is not a doping agent. The S2 category covers GH, GH releasers and secretagogues — the opposite pharmacology

8Open questions

Does native somatostatin infusion still add anything in variceal bleeding on top of modern endoscopic therapy and terlipressin, or is the evidence base too old to guide current practice?
Why has the strong mechanistic rationale in acute pancreatitis never produced a clinical benefit?
Can subtype-selective ligands separate the useful inhibitory effects from the metabolic ones better than the current analogues do?
What is the significance of somatostatin interneuron loss in Alzheimer's disease and depression, and is it addressable at all given the blood–brain barrier?

9References

1Brazeau P et al. (1973). Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. PubMed · DOI
2Patel YC (1999). Somatostatin and its receptor family. Front Neuroendocrinol. PubMed · DOI
3Imperiale TF, Teres D, Birgisson S (1995). Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal haemorrhage: a meta-analysis [verify exact title]. Ann Intern Med. PubMed
4Avgerinos A et al. (1997). Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Lancet. PubMed · DOI
5Gurusamy KS et al. (2013). Somatostatin analogues for pancreatic surgery. Cochrane Database Syst Rev. PubMed · DOI
6Günther T, Tulipano G, Dournaud P et al. (2018). International Union of Basic and Clinical Pharmacology. CV. Somatostatin receptors: structure, function, ligands, and new nomenclature. Pharmacol Rev. PubMed · DOI
7Reichlin S (1983). Somatostatin. NEJM. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

forum threads →

community protocols include this →

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

Licensed CC BY-NC-SA 4.0. Found an error? Report it · Editorial standards — corrections are logged here.