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approvedGrowth Hormone

Pasireotide

Also known as: Signifor, Signifor LAR, SOM230

Pasireotide is a second-generation somatostatin analog with broad receptor binding across SSTR1, SSTR2, SSTR3, and SSTR5 — notably 40× higher SSTR5 affinity than octreotide. FDA-approved as Signifor (2012) for Cushing disease and Signifor LAR (2014) for acromegaly in patients not controlled by first-generation analogs. It is the only medical therapy specifically indicated for Cushing disease, targeting SSTR5 on corticotroph adenomas to suppress excess ACTH secretion.

4 cited references·5 researched benefits

Quick Answer

Pasireotide (Signifor) is a multi-receptor somatostatin analog with uniquely high SSTR5 affinity, FDA-approved for Cushing disease and acromegaly. It is the only somatostatin analog that effectively targets pituitary corticotroph tumors (which express SSTR5 predominantly), reducing ACTH and cortisol levels. For acromegaly, it serves as second-line therapy for patients who fail octreotide or lanreotide. Its main limitation is significant hyperglycemia risk (73% incidence) due to potent insulin suppression.

Key Facts

Mechanism
Pasireotide is a cyclic hexapeptide with broad somatostatin receptor affinity: SSTR5 (40× octreotide), SSTR1 (30×), SSTR3 (5×), and SSTR2 (2.5× less). In Cushing disease, ACTH-secreting pituitary corticotroph adenomas predominantly express SSTR5, making them resistant to octreotide/lanreotide (SSTR2-preferring). Pasireotide's high SSTR5 affinity enables suppression of ACTH secretion from these tumors. In acromegaly, broader receptor engagement (SSTR1/2/3/5 vs SSTR2 alone) provides additional GH suppression in somatostatin analog-resistant patients. The multi-receptor profile also potently suppresses insulin secretion via pancreatic SSTR5, explaining the high hyperglycemia incidence.
Research Status
approved
Half-Life
~12 hours (SC); ~16–19 days (LAR depot)
Molecular Formula
C₅₈H₆₄N₁₀O₉
Primary Use
Growth Hormone
Table of Contents

Benefits

  • Cushing disease treatment — only somatostatin analog approved for Cushing disease; normalizes urinary free cortisol in 25–30% of patientsstrong
  • Second-line acromegaly control — biochemical control in 15–20% of patients who fail first-generation analogs (octreotide/lanreotide)strong
  • Broader receptor coverage — multi-SSTR targeting may benefit tumors with heterogeneous receptor expressionmoderate
  • Tumor volume reduction — reduces corticotroph and somatotroph adenoma volume in some patientsmoderate
  • Cushing syndrome symptom improvement — reduces signs/symptoms including weight, blood pressure, and metabolic abnormalitiesmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (Signifor, Cushing disease)0.3–0.9 mgTwice dailyStart at 0.6 mg twice daily; adjust based on urinary free cortisol response and tolerability. Rotating injection sites (thigh, abdomen) recommended.
Intramuscular depot (Signifor LAR, acromegaly)20–60 mgEvery 28 daysStart at 40 mg monthly for acromegaly patients inadequately controlled on octreotide or lanreotide. May increase to 60 mg or decrease to 20 mg based on GH/IGF-1 response. Glucose monitoring essential.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Hyperglycemia — occurs in 70–75% of patients; the most significant clinical limitation, requiring diabetes management in many patientsserious
  • Gallstones — cholelithiasis in 25–30% with long-term use, higher rate than first-generation analogscommon
  • Diarrhea — gastrointestinal effects in 15–20% of patientscommon
  • Nausea and abdominal pain — GI discomfort in 15–25%, typically during initial treatmentcommon
  • QTc prolongation — modest QTc increase; monitor ECG in patients with cardiac riskrare

Frequently Asked Questions

Why does pasireotide cause more hyperglycemia than octreotide?
Pasireotide has 40× higher SSTR5 affinity than octreotide. SSTR5 is the primary somatostatin receptor on pancreatic beta cells that mediates insulin suppression. This potent SSTR5 activity directly inhibits insulin secretion, causing glucose levels to rise. Additionally, pasireotide suppresses incretin hormones (GLP-1, GIP). The combination of reduced insulin secretion and reduced incretin effect produces clinically significant hyperglycemia in ~73% of patients, with ~40% requiring new diabetes medication initiation.
What is Cushing disease and why is it hard to treat?
Cushing disease specifically refers to excess cortisol production caused by an ACTH-secreting pituitary adenoma (as opposed to Cushing syndrome, which includes all causes of hypercortisolism). Treatment is challenging because: (1) transsphenoidal surgery fails in 20–30% of cases; (2) radiation takes months to years for full effect; (3) corticotroph tumors resist first-generation somatostatin analogs because they express SSTR5, not SSTR2. Pasireotide addresses the SSTR5 gap, but its hyperglycemia limits tolerability.
When should pasireotide be used instead of octreotide for acromegaly?
Pasireotide LAR is reserved for acromegaly patients who remain uncontrolled (IGF-1 above normal) on maximum-dose octreotide LAR or lanreotide for at least 6 months. It may also be considered for tumors with mixed SSTR profiles (SSTR5-expressing in addition to SSTR2). The PAOLA study showed that switching from octreotide/lanreotide to pasireotide LAR 60 mg normalized IGF-1 in an additional 15–20% of resistant patients. However, the high hyperglycemia risk must be weighed against the incremental benefit.
How is pasireotide-induced hyperglycemia managed?
Expert guidelines recommend: (1) baseline glucose assessment before starting pasireotide; (2) metformin as first-line if hyperglycemia develops; (3) DPP-4 inhibitors or GLP-1 RAs as second-line, since pasireotide suppresses incretins; (4) insulin if needed. Sulfonylureas are less effective because pasireotide directly blocks insulin secretion. Close glucose monitoring (weekly initially, then monthly) is mandatory. In some patients, the hyperglycemia is severe enough to require discontinuation.
Is pasireotide used for neuroendocrine tumors?
While octreotide and lanreotide are the standard somatostatin analogs for NETs (based on PROMID and CLARINET trials), pasireotide has been studied in NET patients who progress on first-generation analogs. Results have been mixed — some patients benefit from broader SSTR coverage, but the hyperglycemia burden is significant. Pasireotide is not FDA-approved for NETs. For NET patients who progress on octreotide/lanreotide, other options (PRRT with lutetium-177, everolimus, sunitinib) are generally preferred.

References

  1. 1
    Pasireotide treatment significantly reduces urinary free cortisol in Cushing disease: phase 3 trial results(2012)PubMed ↗
  2. 2
    Pasireotide LAR versus octreotide LAR in acromegaly: a head-to-head phase 3 trial (PAOLA)(2014)PubMed ↗
  3. 3
    Management of pasireotide-associated hyperglycemia: an expert consensus(2017)PubMed ↗
  4. 4
    Somatostatin receptor subtypes in pituitary adenomas and clinical implications(2011)PubMed ↗

Latest Research

Last updated: 2026-02-19