Somatostatin
The body's off-switch for many hormones, given by infusion for bleeding varices in some countries and never approved in the US
Somatostatin is a hormone that inhibits the release of growth hormone, insulin, glucagon and many gut secretions. Native somatostatin is given by continuous infusion in some countries for bleeding oesophageal varices and fistulas; it has never been approved in the US. Its longer-lasting analogues, octreotide and lanreotide, are what most patients receive.
What is it?
Somatostatin is made by nerve, gut, pancreatic and immune cells and acts as a brake: it inhibits the release of growth hormone, insulin and glucagon, slows gut secretions and reduces cell growth. It works through five receptor subtypes. The natural forms, of 14 and 28 amino acids, bind all five; the short synthetic analogues bind mainly subtypes 2, 3 and 5.
Native somatostatin is a hospital drug in some countries. In Spain it is approved for bleeding from ruptured oesophageal varices, alongside endoscopic and surgical treatment, and for high-output pancreatic fistulas, at about 3.5 µg/kg an hour. In Singapore the label adds severe upper gastrointestinal bleeding and other fistulas, starting with a 250 µg injection then 250 µg an hour. It has never been approved in the US, where Drugs@FDA holds no record of it.
For variceal bleeding, a trial of 780 patients found it as effective as terlipressin or octreotide alongside endoscopy, with 5-day success around 84% to 86% in each arm. For pancreatic surgery the picture is mixed: a 120-hour infusion halved clinically relevant fistula in intermediate-risk patients, but it was no better than octreotide in the 651-patient PREFIPS trial, and a pooled analysis of somatostatin and its analogues after pancreaticoduodenectomy found no clear benefit.
Pancreatitis after ERCP is where the evidence leans most in its favour. One trial cut it from 9.6% to 3.6%, and pooled trials found a 37% lower risk, though mainly in Asian studies and at higher doses; added to indomethacin, the extra benefit was not significant. In severe acute pancreatitis it reduced surgical interventions but not deaths, and in external intestinal fistulas it shortened time to closure without changing whether they closed.
Its analogues inherited its job: octreotide, lanreotide and pasireotide treat acromegaly and neuroendocrine tumours, and radiolabelled versions image those tumours.
Mechanism of Action
Somatostatin is a natural 14- or 28-amino-acid peptide that binds all five somatostatin receptors and switches off secretion of hormones and gut juices.
Hormone brake
Inhibits release of growth hormone, insulin and glucagon.
Less gut and pancreatic secretion
Slows gut and pancreatic secretion; trials have used it for fistulas, pancreatitis after ERCP and variceal bleeding.
All five receptors
Binds SSTR1 to SSTR5 with high affinity; octreotide and lanreotide bind mainly 2, 3 and 5.
Published Research
These are the studies that describe somatostatin, read from their PubMed abstracts: a pancreatitis trial and two reviews of its receptors.
Severe acute pancreatitis
50 patients in intensive care received conventional treatment with or without somatostatin for ten days. Surgical interventions fell from 86.4% to 45.8%, but hospital stay and intensive care mortality did not differ.
PREFIPS: against octreotide after pancreatic surgery
In 651 patients randomised after pancreatectomy, grade B/C pancreatic fistula occurred in 24.1% on continuous intravenous somatostatin and 22.9% on subcutaneous octreotide, with no significant difference.
Fistula prevention in intermediate-risk patients
In 199 intermediate-risk patients after pancreaticoduodenectomy, somatostatin 250 µg/h for 120 hours lowered clinically relevant fistula from 25% to 13%, with more delayed gastric emptying (33% against 21%).
Variceal bleeding: three drugs compared
In 780 patients with variceal bleeding given a vasoactive drug before endoscopy, 5-day success was 86.2% with terlipressin, 83.4% with somatostatin and 83.8% with octreotide.
Pancreatitis after ERCP
In 391 patients having therapeutic ERCP, pancreatitis occurred in 3.6% given somatostatin against 9.6% on placebo.
Added to indomethacin before ERCP
In 376 high-risk patients given rectal indomethacin, adding intravenous somatostatin lowered post-ERCP pancreatitis from 15.2% to 11.4%, a difference that was not significant.
With indomethacin in high-risk ERCP
In high-risk patients, indomethacin and somatostatin each eased post-ERCP hyperamylasaemia, and together they reduced it further; the authors suggest somatostatin for complicated, longer procedures with more expected pain.
The receptor family
Somatostatin acts through five G-protein-coupled receptors, SSTR1 to SSTR5. The natural 14- and 28-amino-acid forms bind all five with high affinity; short synthetic analogues bind well only to subtypes 2, 3 and 5.
From signalling to clinic
A review of how somatostatin receptors suppress tumour growth, which led to multireceptor analogues and combination therapies for pituitary and neuroendocrine tumours, and to radiolabelled analogues for imaging and treatment.
ERCP pancreatitis: eleven trials
Across 11 trials and 4,192 patients, somatostatin reduced post-ERCP pancreatitis (risk ratio 0.63) and hyperamylasaemia, with the benefit seen in Asian trials and with a bolus, long infusion or doses above 3,000 µg; abdominal pain did not change.
After pancreaticoduodenectomy: no clear benefit
Across 12 trials of somatostatin and its analogues in 1,615 patients after pancreaticoduodenectomy, neither overall nor clinically relevant fistula fell significantly (odds ratios 0.73 and 0.48), nor did other complications.
External intestinal fistulas
Across trials of somatostatin-based therapy for external gastrointestinal fistulas, closure rates did not differ from control, but fistulas closed about 6 days sooner and hospital stay was about 4 days shorter.
Dosing Data
Native somatostatin is a hospital infusion, not approved in the US. A fistula-prevention trial gave 250 µg an hour for 120 hours; Singapore's label starts with a 250 µg injection, then 250 µg an hour.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the labels where it is approved.
Contraindications & Cautions
Set by the foreign labels.
Legal Status
Native somatostatin is approved in some countries and not in the US.
Frequently Asked Questions
?What is somatostatin?
A hormone that inhibits the release of growth hormone, insulin, glucagon and gut secretions, through five receptor subtypes.
?Is it approved in the US?
No. Drugs@FDA has no record of it. It is approved in some countries, such as Spain, for bleeding varices.
?How does it relate to octreotide?
Octreotide is a longer-lasting synthetic analogue that binds mainly three of its five receptors.
?How is it given?
By continuous intravenous infusion in hospital, about 250 µg an hour where it is approved.
?Is it better than octreotide?
Not in the trials that compared them. For variceal bleeding, 5-day success was 83.4% with somatostatin and 83.8% with octreotide; after pancreatic surgery, fistula rates were 24.1% and 22.9%. Octreotide is injected under the skin, while somatostatin needs a continuous infusion.
?Does it prevent pancreatitis after ERCP?
Probably somewhat. One trial cut it from 9.6% to 3.6%, and pooled trials found about a third lower risk, mainly in Asian studies and with a bolus, long infusion or higher doses. Added to rectal indomethacin, the extra effect was not significant.
?Does it help intestinal fistulas close?
Pooled trials of somatostatin-based treatment found fistulas did not close more often, but they closed about six days sooner and patients left hospital about four days earlier.
References
- [pubmed] Planas M, et al. "Severe acute pancreatitis: treatment with somatostatin." Intensive Care Med, 1998;24(1):37-9. PMID: 9503220.
- [pubmed] Patel YC. "Somatostatin and its receptor family." Front Neuroendocrinol, 1999;20(3):157-98. PMID: 10433861.
- [pubmed] Theodoropoulou M, et al. "Somatostatin receptors: from signaling to clinical practice." Front Neuroendocrinol, 2013;34(3):228-52. PMID: 23872332.
- [pubmed] Brazeau P, et al. "Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone." Science, 1973;179(4068):77-9. PMID: 4682131.
- [pubmed] Cervin C, et al. "A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers." Eur J Pharm Sci, 2009;36(4-5):377-85. PMID: 19041716.
- [other] Spanish Agency of Medicines (AEMPS), Somatostatina GP-Pharm 3 mg product information (ficha técnica): variceal bleeding and pancreatic fistulas, 3.5 µg/kg per hour. Read September 30, 2026.
- [other] Singapore National Drug Formulary, Stilamin 3000 (somatostatin) product information: upper gastrointestinal bleeding and fistulas, 250 µg then 250 µg per hour. Read September 30, 2026.
- [other] US FDA, Drugs@FDA (openFDA): no record for somatostatin. Read September 30, 2026.
- [clinical-trial] Gaujoux S, et al. "Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial: A FRENCH 007-ACHBT Study." Ann Surg, 2024;280(2):179-187. PMID: 38662619.
- [clinical-trial] Cao Z, et al. "A randomised, multicentre trial of somatostatin to prevent clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy." J Gastroenterol, 2021;56(10):938-948. PMID: 34453212.
- [clinical-trial] Seo YS, et al. "Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage." Hepatology, 2014;60(3):954-63. PMID: 24415445.
- [clinical-trial] Lee KT, et al. "The prophylactic effect of somatostatin on post-therapeutic endoscopic retrograde cholangiopancreatography pancreatitis: a randomized, multicenter controlled trial." Pancreas, 2008;37(4):445-8. PMID: 18953260.
- [pubmed] Norouzi A, et al. "Effect of Adding Intravenous Somatostatin to Rectal Indomethacin on Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis in High-risk Patients: A Double-blind Randomized Placebo-controlled Clinical Trial." J Clin Gastroenterol, 2023;57(2):204-210. PMID: 34049378.
- [pubmed] Hu J, et al. "Role of Somatostatin in Preventing Post-endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis: An Update Meta-analysis." Front Pharmacol, 2016;7:489. PMID: 28018225.
- [pubmed] Adiamah A, et al. "The Use of Prophylactic Somatostatin Therapy Following Pancreaticoduodenectomy: A Meta-analysis of Randomised Controlled Trials." World J Surg, 2019;43(7):1788-1801. PMID: 30798417.
- [pubmed] Ribeiro Junior MAF, et al. "Somatostatin-based therapies for external gastrointestinal fistulas: Updated meta-analysis of randomized clinical trials." World J Gastrointest Pharmacol Ther, 2025;16(4):111889. PMID: 41378069.
- [pubmed] Wu Z, et al. "Effects of Somatostatin and Indomethacin Mono or Combination Therapy on High-risk Hyperamylasemia and Post-pancreatitis Endoscopic Retrograde Cholangiopancreatography Patients: A Randomized Study." Surg Laparosc Endosc Percutan Tech, 2023;33(5):474-479. PMID: 37523580.
Sources & Citations
Studies were read from their PubMed abstracts; Spanish and Singaporean labels were read earlier for the approved uses. Read October 6, 2026.
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