Quick summary
Pasireotide (Signifor) is an FDA-approved cyclic hexapeptide somatostatin analog with uniquely broad receptor binding (SSTR1, 2, 3, 5). It is the first pituitary-directed therapy for Cushing's disease and is also approved for acromegaly, though hyperglycemia affects 60-80% of patients.
Overview
Pasireotide (brand: Signifor) is an FDA-approved cyclic hexapeptide somatostatin analog with a unique multi-receptor binding profile. It is the first pituitary-directed therapy approved for Cushing's disease and also approved for acromegaly (Signifor LAR). Its higher binding affinity for SSTR1, 3, and 5 distinguishes it from octreotide and lanreotide.
Mechanism of action
Pasireotide activates somatostatin receptors SSTR1, 2, 3, and 5, with particularly high affinity for SSTR5, which is overexpressed in corticotroph adenoma cells in Cushing's disease. SSTR5 engagement suppresses ACTH secretion from pituitary adenomas, reducing cortisol production. In acromegaly, combined SSTR2/5 activity more comprehensively inhibits GH secretion than SSTR2-selective agents. Compared to octreotide, pasireotide has 40-fold greater binding affinity for SSTR5.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| Cushing's disease | subcutaneous | 600–900 mcg | twice daily | Start at 600 mcg SC BID; increase to 900 mcg BID if UFC not normalized after 2 months |
| acromegaly (LAR formulation) | intramuscular | 40–60 mg | every 4 weeks | Signifor LAR formulation; dose based on GH/IGF-1 response |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
The PASPORT phase III trial demonstrated pasireotide normalized urinary free cortisol (UFC) in ~25% of Cushing's disease patients at 6 months, with sustained response at 24 months. FDA approval for Cushing's disease was granted December 2012. Signifor LAR was approved for acromegaly in 2014. Major limitation: hyperglycemia occurs in 60–80% of patients, requiring glucose-lowering medication. Ongoing research explores its role in ACTH-secreting tumors and combination regimens.[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Pasireotide for synergistic effects.
Legal status
FDA-approved (NDA 203255, December 2012) for Cushing's disease and acromegaly. Available as Signifor (SC, twice daily) for Cushing's and Signifor LAR (IM, monthly) for acromegaly. Prescription-only.
Sourcing & access
Prescription required
Pasireotide is an FDA-approved prescription medication available through licensed healthcare providers, telehealth platforms, and 503A/503B compounding pharmacies.
Frequently asked questions
Pasireotide (Signifor) is FDA-approved for two indications: Cushing's disease since December 2012 and acromegaly (Signifor LAR, monthly IM) since 2014. It is the first pituitary-directed medical therapy specifically approved for Cushing's disease, addressing the underlying corticotroph adenoma rather than just downstream cortisol effects, and provides a non-surgical option for patients whose adenomas can't be fully resected.
Pasireotide activates somatostatin receptors SSTR1, 2, 3, and 5, with 40-fold greater affinity for SSTR5 than octreotide. SSTR5 is overexpressed in corticotroph adenomas in Cushing's disease, and its engagement suppresses ACTH secretion, reducing cortisol production.
The major limitation is hyperglycemia, which occurs in 60-80% of patients and often requires glucose-lowering medication. Other side effects include diarrhea, gallstone formation, abdominal pain, nausea, bradycardia, and QT prolongation.
Pasireotide has a much broader somatostatin receptor binding profile, with particularly high affinity for SSTR5 (40-fold greater than octreotide). This makes it effective for Cushing's disease where SSTR5 is the dominant receptor on corticotroph tumors, while octreotide primarily targets SSTR2.
The Phase III PASPORT trial demonstrated pasireotide normalized urinary free cortisol in approximately 25% of Cushing's disease patients at 6 months, with sustained response at 24 months. This led to FDA approval as the first medical therapy targeting the pituitary cause of Cushing's disease.
Research references
- Pasireotide for acromegaly: phase III trial comparing to octreotidePubMed
- Pasireotide in Cushing's disease: 12-month efficacy and safety dataPubMed
- Pasireotide LAR in neuroendocrine tumors: long-acting formulation phase II studyPubMed
- Multi-receptor somatostatin analog pasireotide: pharmacology and clinical utilityPubMed