Somatostatin
Evidence: DEvidence: AGrade D — Applies to native Somatostatin (SST-14 and SST-28), administered intravenously to small human cohorts in controlled physiologic/mechanistic studies (Klaff 1983, PMID 6137927, both forms compared; Phillip 1977, PMID 866987, SS-14; Cappa 1999, PMID 10599697, SS-14, pediatric). This reflects genuine direct-human evidence of Somatostatin's pancreatic-hormone-suppressing, gastric-acid-suppressing, and GH-axis effects, but the evidence base is entirely small acute-infusion or infusion-withdrawal physiology studies, not a therapeutic-outcome or larger RCT base, consistent with somatostatin's ultra-short (~1-3 minute) plasma half-life precluding standalone clinical use. SST-14 and SST-28 show a real potency difference for insulin suppression (SST-28 more potent) that must not be silently merged in any insulin-specific claim; they are equipotent for glucagon/pancreatic-polypeptide suppression, which may be stated for both forms together..
Grade A — Octreotide and Lanreotide somatostatin-analogue clinical and regulatory programmes.
Octreotide (Sandostatin, FDA-approved 1988) and Lanreotide (Somatuline Depot, FDA-approved 2007) are sequence-modified synthetic analogues of native somatostatin, not native somatostatin itself. Both are FDA-approved somatostatin analogues with strong clinical/regulatory programmes and overlapping but NOT identical indications: both are FDA-approved for acromegaly. Octreotide is labeled for symptomatic treatment of severe diarrhea and flushing associated with metastatic carcinoid tumors, and for profuse watery diarrhea associated with VIP-secreting tumors (VIPomas); its official label explicitly states that improvement in tumor size or growth rate was NOT shown in the clinical trials performed with Sandostatin Injection. Lanreotide is labeled for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival (added 2014, CLARINET trial) and for carcinoid syndrome, to reduce the frequency of short-acting somatostatin-analog rescue therapy (added 2017, ELECT trial). Octreotide does NOT carry a GEP-NET or general tumor-control indication on its official label. None of these approvals -- for either drug, in any indication -- upgrades native somatostatin's own evidence grade (D). Native somatostatin itself has an ultra-short plasma half-life (~1-3 minutes) that precludes standalone therapeutic use; its own evidence grade reflects genuine but short-lived, physiologic/diagnostic-only human data, entirely separate from these two products' own large, FDA-approval-grade clinical programmes. Product approvals, dosing, and safety profiles described here are specific to Octreotide and Lanreotide as distinct regulated products with distinct indications, not to somatostatin as a molecule class, and not to each other.
Gastrointestinal / Gut-Hormone Signaling
Evidence Snapshot
What this grade covers
Applies to native Somatostatin (SST-14 and SST-28), administered intravenously to small human cohorts in controlled physiologic/mechanistic studies (Klaff 1983, PMID 6137927, both forms compared; Phillip 1977, PMID 866987, SS-14; Cappa 1999, PMID 10599697, SS-14, pediatric). This reflects genuine direct-human evidence of Somatostatin's pancreatic-hormone-suppressing, gastric-acid-suppressing, and GH-axis effects, but the evidence base is entirely small acute-infusion or infusion-withdrawal physiology studies, not a therapeutic-outcome or larger RCT base, consistent with somatostatin's ultra-short (~1-3 minute) plasma half-life precluding standalone clinical use. SST-14 and SST-28 show a real potency difference for insulin suppression (SST-28 more potent) that must not be silently merged in any insulin-specific claim; they are equipotent for glucagon/pancreatic-polypeptide suppression, which may be stated for both forms together.
Regulatory Context
Native Somatostatin is an endogenous hormone and is not itself an FDA-approved drug product. Octreotide (Sandostatin, approved 1988) and Lanreotide (Somatuline Depot, approved 2007) are FDA-approved synthetic analogues with overlapping but distinct indications: both are approved for acromegaly; Lanreotide is additionally approved for gastroenteropancreatic neuroendocrine tumors (GEP-NETs, to improve progression-free survival) and for carcinoid syndrome; Octreotide is additionally approved for symptomatic control of diarrhea and flushing in metastatic carcinoid tumors and for VIPoma-associated diarrhea, with its official label explicitly stating that improvement in tumor size or growth rate was not shown in the trials performed with Sandostatin Injection. Their regulatory status, dosing, and safety profile are specific to those products and their specific indications, and do not apply to native somatostatin.
Research Takeaway
Somatostatin (SST, SRIF, GHIH) is an endogenous cyclic peptide hormone that exists in two major native circulating forms, SST-14 and SST-28, which inhibit growth hormone, insulin, glucagon, and gastric acid secretion, among other effects.
Evidence boundary: Identity/physiology statement. Do not use to imply Octreotide or Lanreotide are native Somatostatin.
See all 6 evidence claims →Quick Summary
Somatostatin (SST, SRIF, GHIH) is the body's primary growth-hormone-inhibiting hormone, circulating in two native forms (SST-14 and SST-28) with some differential potency. Controlled human studies confirm it suppresses insulin, glucagon, and gastric acid secretion, but its extremely short plasma half-life (1-3 minutes) makes native somatostatin itself unsuitable as a standalone drug. Two long-acting, sequence-modified synthetic analogues, Octreotide (Sandostatin) and Lanreotide (Somatuline Depot), are FDA-approved medicines for acromegaly (both drugs); Lanreotide is additionally approved for certain neuroendocrine tumors (GEP-NETs, to improve progression-free survival) and for carcinoid syndrome, while Octreotide is additionally approved for symptom control (diarrhea and flushing) in metastatic carcinoid tumors and for VIPoma-associated diarrhea, not for tumor control -- but their approval and clinical results belong to those specific drug products and specific indications, not to native somatostatin itself or to each other.
Mechanism & Research Overview
Somatostatin (SST, SRIF, GHIH) is the body's primary growth-hormone-inhibiting hormone, circulating in two native forms (SST-14 and SST-28) with some differential potency. Controlled human studies confirm it suppresses insulin, glucagon, and gastric acid secretion, but its extremely short plasma half-life (1-3 minutes) makes native somatostatin itself unsuitable as a standalone drug. Two long-acting, sequence-modified synthetic analogues, Octreotide (Sandostatin) and Lanreotide (Somatuline Depot), are FDA-approved medicines for acromegaly (both drugs); Lanreotide is additionally approved for certain neuroendocrine tumors (GEP-NETs, to improve progression-free survival) and for carcinoid syndrome, while Octreotide is additionally approved for symptom control (diarrhea and flushing) in metastatic carcinoid tumors and for VIPoma-associated diarrhea, not for tumor control -- but their approval and clinical results belong to those specific drug products and specific indications, not to native somatostatin itself or to each other.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Somatostatin (SST, SRIF, GHIH) is an endogenous cyclic peptide hormone that exists in two major native circulating forms, SST-14 and SST-28, which inhibit growth hormone, insulin, glucagon, and gastric acid secretion, among other effects.
Does not establish
Evidence boundary: Identity/physiology statement. Do not use to imply Octreotide or Lanreotide are native Somatostatin.
Sources: Inhibition of Pancreatic Hormone Secretion by Somatostatin-28 and Somatostatin-14 in Man
Supported
In a controlled human comparison, somatostatin-28 more effectively suppressed arginine-induced insulin secretion than somatostatin-14, while both forms equally suppressed glucagon and pancreatic-polypeptide release.
Does not establish
Evidence boundary: Single small (n=5) human study; must not be generalized beyond the arginine-stimulation model tested. Do not state SST-14 and SST-28 are equally potent for insulin suppression.
Sources: Inhibition of Pancreatic Hormone Secretion by Somatostatin-28 and Somatostatin-14 in Man
Supported
Intravenous native somatostatin (SS-14) substantially inhibits both pentagastrin-stimulated and meal-stimulated gastric acid secretion in humans, largely through a direct effect on parietal cells rather than solely through gastrin suppression.
Does not establish
Evidence boundary: Single small (n=6) 1977 study; acute infusion only.
Supported
Withdrawal of a somatostatin infusion produces a rebound rise in growth hormone in children with normal GH-axis function; this rebound is markedly blunted in children with growth hormone deficiency or neurosecretory dysfunction.
Does not establish
Evidence boundary: PEDIATRIC POPULATION ONLY (ages ~3.7-11.1 years); not established in adults in this review, and must not be presented as an adult finding without further sourcing.
Supported
Octreotide and Lanreotide are sequence-modified synthetic analogues of native somatostatin, not native somatostatin itself. Their indications overlap but are not identical: both are FDA-approved for acromegaly. Octreotide is labeled for symptomatic control of severe diarrhea and flushing associated with metastatic carcinoid tumors and for VIPoma-associated watery diarrhea (its label states tumor-size/growth-rate improvement was not shown). Lanreotide is labeled for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival and for carcinoid syndrome. These product-specific, non-identical approvals do not establish native somatostatin's own efficacy, safety, dosing, or regulatory status.
Does not establish
Evidence boundary: Never state or imply native somatostatin is FDA-approved for any indication. Never state or imply Octreotide is approved for GEP-NETs, tumor-size reduction, or general tumor control -- its label explicitly states this was not shown. Never present Octreotide and Lanreotide's indications as identical.
Sources: FDA Label / DailyMed Record for SANDOSTATIN (Octreotide Acetate) Injection; FDA Label / DailyMed Record for SOMATULINE DEPOT (Lanreotide) Injection
Supported
Cortistatin-14/17 is a structurally related but distinct peptide, covered as its own separate subject. Studies designed to characterize Cortistatin's endocrine activity, which use somatostatin as a reference comparator, are Cortistatin's own primary evidence and are not counted as primary native-Somatostatin evidence on this page.
Does not establish
Evidence boundary: Firewall statement. Do not cite PMID 14594107, 12161511, or 15336231 as primary native-Somatostatin efficacy evidence; cross-reference for identity/context only.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Official labels document substantial product-specific adverse-event rates for these analogues (e.g., Octreotide: 63% biliary abnormalities in chronic users, 25% bradycardia in acromegalic patients; Lanreotide: cholelithiasis, glucose dysregulation, sinus bradycardia, thyroid suppression, steatorrhea). These are real risks of the APPROVED DRUG PRODUCTS, not of native somatostatin, and must be labeled as such wherever presented.Safety Consideration
A controlled pediatric study found a marked rebound rise in growth hormone after stopping a somatostatin infusion in children with normal GH-axis function (PMID 10599697) -- a genuine physiological caution relevant to any diagnostic or research use of somatostatin infusion in this population.Safety Consideration
SST-28 is more potent than SST-14 for insulin suppression specifically; treating the two forms as interchangeable for this endpoint would misstate the verified human evidence (PMID 6137927).Safety Consideration
Native somatostatin's plasma half-life of approximately 1-3 minutes is the primary reason no native-somatostatin drug product exists; this is the central rationale for the entire Octreotide/Lanreotide analogue development programme.
Research Areas Being Studied
Research areas discussed on this page reflect the Gastrointestinal / Gut-Hormone Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Somatostatin Infusion Withdrawal: Studies in Normal Children and in Children with Growth Hormone Deficiency (1999):
- Inhibition of Pancreatic Hormone Secretion by Somatostatin-28 and Somatostatin-14 in Man (1983):
- Inhibition by Somatostatin of Gastrin Release and Gastric Acid Responses to Meals and to Pentagastrin in Man (1977):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Somatostatin Infusion Withdrawal: Studies in Normal Children and in Children with Growth Hormone Deficiency | 1999 | 28 prepubertal children (18 normal short-stature controls, 6 GH-deficient, 4 GH-neurosecretory-dysfunction) | Withdrawal of a somatostatin infusion produced a marked rebound GH rise in normal children (13.7±1.0 microg/L) vs. minimal rebound in GH-deficient (1.6±0.4 microg/L) and neurosecretory-dysfunction (2.4±0.3 microg/L) children, fully discriminating the groups. | PEDIATRIC POPULATION ONLY (ages ~3.7-11.1 years) -- must not be generalized to adults without qualification. | |
| Inhibition of Pancreatic Hormone Secretion by Somatostatin-28 and Somatostatin-14 in Man | 1983 | 5 normal male subjects | In 210-minute infusions of both native forms, SS-28 was more effective than SS-14 at suppressing arginine-induced insulin secretion; both forms equally suppressed glucagon and pancreatic-polypeptide release; plasma somatostatin levels were ~28% lower during SS-14 infusion than SS-28 infusion at matched dosing. | SST-14/SST-28 potency differ for insulin suppression specifically -- must not be presented as equipotent for that endpoint. | |
| Inhibition by Somatostatin of Gastrin Release and Gastric Acid Responses to Meals and to Pentagastrin in Man | 1977 | 6 subjects | IV native cyclic somatostatin (SS-14, 5 microg/kg-h) produced ~70% inhibition of pentagastrin-stimulated 1-hour acid output and ~75% inhibition of meal-stimulated acid output (90-95% in the final 30 minutes), while serum gastrin fell only ~30%, implying a substantial direct-parietal-cell (not purely gastrin-mediated) mechanism. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| FDA Label / DailyMed Record for SOMATULINE DEPOT (Lanreotide) Injection | 2007 | Lanreotide (Somatuline Depot), a synthetic cyclical octapeptide analogue of somatostatin, is FDA-approved for: (1) long-term treatment of acromegalic patients with inadequate response to surgery/radiotherapy (2007); (2) treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival (2014, CLARINET trial, 53% PFS improvement vs. placebo, 264 patients); (3) treatment of adults with carcinoid syndrome, reducing the frequency of short-acting somatostatin-analog rescue therapy (2017, ELECT trial). Label warnings: cholelithiasis/gallbladder complications, hyperglycemia/hypoglycemia, sinus bradycardia, mild thyroid-function decreases, new-onset steatorrhea. | These three indications are Lanreotide-specific and are NOT shared by Octreotide -- Octreotide's label carries no GEP-NET or general tumor-control indication (see companion Octreotide source). Product-specific; does not establish native somatostatin's own efficacy or safety. | No source link available | |
| FDA Label / DailyMed Record for SANDOSTATIN (Octreotide Acetate) Injection | 1988 | Octreotide (Sandostatin), a synthetic cyclic octapeptide analogue of somatostatin, FDA-approved since 1988: (1) to reduce GH/IGF-1 in acromegaly patients with inadequate response to surgery/irradiation/bromocriptine; (2) for symptomatic treatment of severe diarrhea and flushing associated with metastatic carcinoid tumors; (3) for profuse watery diarrhea associated with VIP-secreting tumors (VIPomas). Label states verbatim: 'Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with Sandostatin Injection; these trials were not optimally designed to detect such effects.' Label-documented adverse-event rates: bradycardia in 25% of acromegalic patients; biliary abnormalities in 63% of chronic users (52% at 12+ months); hyperglycemia in 16%/hypoglycemia in 3%; hypothyroidism in 12%. | No GEP-NET or general tumor-control indication exists on this label -- must not be confused with Lanreotide's separate GEP-NET indication. Product-specific; does not establish native somatostatin's own efficacy or safety. | No source link available |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research on endogenous somatostatin and its FDA-approved analogue drugs, Octreotide and Lanreotide. It does not constitute medical advice, a treatment recommendation, or dosing guidance for any somatostatin-related substance or its analogue drug products.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-26.
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