Somatostatin-14

The native 14-amino-acid hypothalamic and gut hormone that inhibits growth hormone, insulin, glucagon and splanchnic blood flow, sold abroad as a hospital infusion for variceal bleeding but never approved in the United States, where octreotide is the clinical analog.

Also referenced as: Somatostatin, SRIF-14, SRIF, SS-14, GHIH, Somatostatin acetate, Stilamin, Somatostatine Eumedica

Also appears in: Metabolic

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What is Somatostatin-14?

Somatostatin-14 is the native cyclic tetradecapeptide isolated from ovine hypothalamus in 1973 by Brazeau, Vale, Burgus and colleagues in Guillemin’s laboratory, who found that it blocked immunoreactive growth hormone release from pituitary tissue at 1 nM and gave it the sequence H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH (Brazeau et al., Science, 1973;179(4068):77–79). The cysteines at positions 3 and 14 form a disulfide bridge, making the molecule a ring with a two-residue tail; mass spectrometry confirmed the sequence the same year (Ling et al., Biochemical and Biophysical Research Communications, 1973;50(1):127–133). Its molecular formula is C76H104N18O19S2 and its molecular weight 1,637.9 Da. Somatostatin-28 is the same sequence extended at the N-terminus and predominates in the gut (Pradayrol et al., FEBS Letters, 1980;109(1):55–58); both are cleaved from the carboxyl end of one 116-residue preprosomatostatin encoded by a single human gene (Shen et al., Proceedings of the National Academy of Sciences, 1982;79(15):4575–4579). Cortistatin is a separate gene product that shares the receptor-binding core (de Lecea et al., Nature, 1996;381(6579):242–245).

The hormone is made in the hypothalamus, pancreatic delta cells, gut D cells and neurons throughout the brain, and acts as a broad brake on secretion. Because it survives only minutes in blood, stabilized octapeptide analogs replaced it in chronic therapy: SMS 201-995, now octreotide, was reported in 1982 as three times more potent than the native hormone at inhibiting growth hormone secretion in vitro and highly resistant to enzymatic degradation (Bauer et al., Life Sciences, 1982;31(11):1133–1140), followed by lanreotide and pasireotide. Somatostatin-14 is sold in parts of Europe and Asia as a hospital infusion, mainly for acute variceal bleeding, but no US application was ever approved. It is also available as somatostatin acetate on the research-peptide market.

How it works

• Five Gi-coupled receptors. Somatostatin signals through five G protein-coupled receptors, SST1 to SST5, cloned in the early 1990s, which share inhibition of adenylyl cyclase, opening of potassium channels and closing of voltage-gated calcium channels, hyperpolarizing secretory cells and shutting off exocytosis (Yamada et al., Proceedings of the National Academy of Sciences, 1992;89(1):251–255; Reisine and Bell, Endocrine Reviews, 1995;16(4):427–442). Somatostatin-14 binds all five subtypes with nanomolar affinity, whereas octreotide and lanreotide are selective for SST2 and SST5 (Günther et al., Pharmacological Reviews, 2018;70(4):763–835; Patel, Frontiers in Neuroendocrinology, 1999;20(3):157–198).
• Pan-endocrine inhibition. The infused peptide suppresses growth hormone, thyrotropin, insulin, glucagon, gastrin, secretin, cholecystokinin and vasoactive intestinal peptide, along with gastric acid and pancreatic enzyme output, gut motility and nutrient absorption (Reichlin, New England Journal of Medicine, 1983;309(24):1495–1501). In 10 insulin-dependent diabetic subjects, a two-hour infusion lowered fasting plasma glucagon from 150 to 77 pg/mL and glucose from 260 to 191 mg/dL, implicating excess glucagon in diabetic hyperglycemia (Gerich et al., New England Journal of Medicine, 1974;291(11):544–547).
• Selective splanchnic vasoconstriction. In 17 patients with cirrhosis and severe portal hypertension, a 1 µg/kg injection lowered wedged hepatic venous pressure from 19.5 to 14.0 mmHg, and a constant infusion reduced it by 17.0% and estimated hepatic blood flow by 17.5% without changing cardiac output, arterial pressure or peripheral resistance, in contrast to vasopressin, which also lowered cardiac output and raised arterial pressure (Bosch et al., Gastroenterology, 1981;80(3):518–525). This portal effect is the basis of its use in variceal hemorrhage.
• Clearance in minutes. After a constant infusion in healthy volunteers, immunoreactive somatostatin disappeared with an initial half-life of 1.1 to 3.0 minutes and a metabolic clearance rate of about 1,949 mL/min, unchanged in chronic liver disease but reduced to about 501 mL/min in end-stage renal failure (Sheppard et al., Journal of Clinical Endocrinology and Metabolism, 1979;48(1):50–53).

Research status

Variceal bleeding is the main clinical evidence base. The pivotal placebo-controlled trial randomized 120 patients with bleeding esophageal varices to a 5-day somatostatin infusion or placebo. Failure to control bleeding occurred in 22 of 61 (36%) somatostatin patients versus 35 of 59 (59%) on placebo, transfusion per hour fell from a median of 0.105 to 0.033 units, and balloon tamponade use was halved, but 30-day mortality did not differ (9 versus 7 deaths) (Burroughs et al., Gastroenterology, 1990;99(5):1388–1395). The European ABOVE trial randomized 205 cirrhotic patients to natural somatostatin or placebo for 120 hours around emergency sclerotherapy: treatment failed in 35 versus 57 (P = 0.004) and death or rescue therapy occurred in 9 versus 19 (P = 0.05) (Avgerinos et al., Lancet, 1997;350(9090):1495–1499).

Pooled analyses show hemostasis, not clearly survival. A Cochrane review of 21 trials of somatostatin and its analogs in 2,588 patients found no significant reduction in mortality (relative risk 0.97, 95% CI 0.75 to 1.25, in the low-bias trials), about 0.7 fewer units transfused per patient and fewer failures of initial hemostasis (relative risk 0.68, 95% CI 0.54 to 0.87); the authors doubted the transfusion saving was worthwhile (Gøtzsche and Hróbjartsson, Cochrane Database of Systematic Reviews, 2008;(3):CD000193). A meta-analysis of 30 trials and 3,111 patients covering all vasoactive agents found lower 7-day mortality (relative risk 0.74, 95% CI 0.57 to 0.95) with no detectable difference between agents (Wells et al., Alimentary Pharmacology and Therapeutics, 2012;35(11):1267–1278).

Head-to-head with its analogs. A Korean multicenter noninferiority trial randomized 780 patients with variceal bleeding to early terlipressin, somatostatin or octreotide before endoscopic treatment. Five-day treatment success was 86.2%, 83.4% and 83.8% (P = 0.636), rebleeding 3.4%, 4.8% and 4.4%, and mortality 8.0%, 8.9% and 8.8%, with all pairwise comparisons meeting the noninferiority margin (Seo et al., Hepatology, 2014;60(3):954–963). The 2017 AASLD practice guidance and the 2022 Baveno VII consensus list terlipressin, somatostatin and octreotide as interchangeable options in suspected variceal bleeding (Garcia-Tsao et al., Hepatology, 2017;65(1):310–335; de Franchis et al., Journal of Hepatology, 2022;76(4):959–974); in the US only octreotide is available.

Post-ERCP pancreatitis: positive and negative trials. A Chinese open-label multicenter trial of 900 analyzable patients found post-ERCP pancreatitis in 18 of 445 (4.0%) given a somatostatin infusion versus 34 of 455 (7.5%) controls (P = 0.03), with no deaths or perforations (Bai et al., Endoscopy, 2015;47(5):415–420). A Spanish double-blind trial of 510 patients using a bolus plus a short infusion found no benefit, with pancreatitis in 7.5% on somatostatin versus 6.7% on placebo (Concepción-Martín et al., Endoscopy, 2014;46(10):851–856), and an Iranian double-blind trial adding somatostatin to rectal indomethacin in 376 high-risk patients found a nonsignificant difference, 11.4% versus 15.2% (Norouzi et al., Journal of Clinical Gastroenterology, 2023;57(2):204–210). A meta-analysis of 11 trials and 4,192 patients found a lower incidence of pancreatitis overall (relative risk 0.63, 95% CI 0.40 to 0.98), with the benefit confined to Asian trials and to single-bolus, long-infusion or high-total-dose regimens (Hu et al., Frontiers in Pharmacology, 2016;7:489); a second meta-analysis found benefit only with prolonged infusions in high-risk patients (Wang et al., Pancreatology, 2018;18(4):370–378).

Pancreatic surgery and fistula. A Cochrane review of 21 trials and 2,348 people, pooling the native peptide with its analogs, found that prophylaxis reduced pancreatic fistula (relative risk 0.66, 95% CI 0.55 to 0.79) without reducing perioperative mortality (relative risk 0.80, 95% CI 0.56 to 1.16), with no difference in the few trials that distinguished clinically significant fistulas (Gurusamy et al., Cochrane Database of Systematic Reviews, 2013;(4):CD008370).

Registered trials as of November 2026. Active registry entries testing somatostatin as a treatment are small academic studies outside the US. A 72-patient multicenter Chinese trial at Tongji Hospital compares somatostatin plus a clear liquid diet with a prophylactic diverting stoma to prevent anastomotic leakage after ultra-low anterior resection for rectal cancer, recruiting since November 17, 2025 with primary completion estimated for July 31, 2027 (NCT07605611). A 50-patient Turkish study compares somatostatin and terlipressin on portal pressure during living donor liver transplantation (NCT07304466), and a 64-patient Chinese trial of terlipressin versus somatostatin in variceal bleeding with renal dysfunction is not yet recruiting (NCT07252401). In the US and Denmark the native peptide appears only as a physiological tool for clamping endogenous hormone secretion in metabolic studies (NCT03241706, NCT06416969, NCT07366710); no registered US trial is aimed at approval.

Regulatory status abroad. Stilamin, originally a Serono product, is registered in Singapore as a 3 mg powder for injection (SIN06135P) for severe acute upper gastrointestinal hemorrhage, digestive fistulas, postoperative pancreatic complications and diabetic ketoacidosis; Swissmedic’s list of authorized human medicines names Hasten Biopharmaceutic (Switzerland) AG as holder of Stilamin 3 mg powder for solution for infusion. France authorized Somatostatine Eumedica 3 mg powder for solution for infusion on February 9, 1993 as a hospital-only product, and Spain’s AEMPS lists marketed hospital-use generics from GP Pharm (3 mg, first authorized February 14, 2001) and Normon (3 mg and 6 mg, 2007). Drugs@FDA lists no somatostatin application and DailyMed carries no somatostatin label.

Common dosage forms

• Lyophilized powder for infusion, 3 mg. The standard hospital presentation abroad: an ampoule or vial of somatostatin acetate equivalent to 3 mg somatostatin with a solvent ampoule, sold as Stilamin (Singapore, Switzerland), Somatostatine Eumedica (France) and generic somatostatina (Spain).
• Powder for infusion, 6 mg. A larger generic presentation marketed in Spain by Normon.
• Powder for infusion, 0.25 mg. Smaller vials registered in Spain but not currently marketed.
• Research-market vials. Lyophilized somatostatin acetate sold to laboratories, with no pharmaceutical approval in any country.

Key considerations

• Regulatory status. The Research Market status reflects the absence of any FDA-approved somatostatin-14 product, any FDA-recognized compounding standing and any US-directed development program. The peptide is approved as a hospital infusion in France, Spain, Switzerland and Singapore under names including Stilamin and Somatostatine Eumedica, and the US clinical analog is octreotide.
• A hormone that lasts minutes. With a circulating half-life of 1 to 3 minutes, somatostatin-14 has no useful activity beyond the first minutes after a single injection, so every approved use is a continuous infusion and its analogs displaced it for chronic indications.
• Modest and conditional efficacy. The trials show better control of variceal bleeding and fewer transfusions but no convincing mortality benefit, equivalence rather than superiority against terlipressin and octreotide, and benefit in post-ERCP pancreatitis mainly with prolonged infusion in high-risk patients.
• Rebound and metabolic effects. Because the peptide suppresses insulin and glucagon together, infusion can move blood glucose in either direction and withdrawal can release a rebound hormone surge; the controlled trials reported no excess of serious complications.
• Naming. Somatostatin, somatotropin release-inhibiting factor (SRIF-14), SS-14, growth hormone-inhibiting hormone (GHIH), Stilamin and Somatostatine Eumedica all denote the native 14-residue peptide; somatostatin-28 is a longer form from the same precursor, cortistatin is a different gene product, and octreotide, lanreotide and pasireotide are synthetic analogs whose approvals and safety data do not transfer to the native hormone.