Bottom line
Pasireotide is a cyclohexapeptide somatostatin analog with broader receptor binding (SSTR1,2,3,5) than octreotide or lanreotide. Approved for Cushing's disease (SC Signifor, 2012) and acromegaly (IM Signifor LAR, 2014). Unique risk of hyperglycemia including diabetic ketoacidosis, which can be severe and exceeds rates seen with first-generation somatostatin analogs.
Identity and composition
| Field | Verified information |
|---|---|
| Preferred name | Pasireotide |
| Key aliases | Signifor (SC), Signifor LAR (IM), SOM230 |
| Molecular/sequence identity | Cyclohexapeptide: cyclo[(4R)-4-(2-aminoethylcarbamoyloxy)-L-Pro-L-Phe-D-Trp-L-Lys-O-benzyl-L-Tyr-L-Phe]; no disulfide bridge (lacks cysteine residues) |
| Modifications/form | Diaspartate salt; SC solution (Signifor) and IM LAR microsphere suspension (Signifor LAR) |
| Stable identifiers | UNII: 98H1T17066; PubChem CID: 9941444; CAS: 396091-73-9 (base); DrugBank: DB09063 |
| Identity caveats | Structurally distinct from octapeptide somatostatin analogs. Unique aminoethylcarbamoyl modification on Pro residue. |
Development and approval status
| Jurisdiction | Status and indication | Product/source | As of |
|---|---|---|---|
| US (FDA) | Approved: Cushing's disease (SC); acromegaly (LAR) | Signifor / Signifor LAR (Novartis) | Dec 2012 (SC); Dec 2014 (LAR) |
| EU/EEA (EMA) | Approved: Cushing's disease (SC, LAR); acromegaly (LAR) | Signifor | Apr 2012 (SC); Nov 2014 (LAR) |
| UK (MHRA) | Approved: same | Signifor | 2012 |
Mechanism and pharmacology
Multi-receptor somatostatin agonist with high affinity for SSTR5 (Kᵢ ~0.16 nM) and SSTR2 (Kᵢ ~0.16 nM), and moderate affinity for SSTR3 (Kᵢ ~1.1 nM) and SSTR1 (Kᵢ ~2.7 nM). Suppresses ACTH secretion from corticotroph adenomas through SSTR5 agonism, and GH/IGF-1 through SSTR2/5. Broader receptor affinity compared to octreotide/lanreotide, particularly SSTR1 and SSTR5.
Evidence by claim
| Claim/indication | Stage | Grade | Best human evidence | Main result | Important limitations |
|---|---|---|---|---|---|
| Cushing's disease | Approved | A | Phase 3 (CSOM230B2305; Colao A, et al. N Engl J Med. 2012;366:914–24. PMID: 22397653) | UFC normalization at month 6 in 15% (600 mcg) and 26% (900 mcg) SC BID | No comparator; high dropout rate |
| Acromegaly (inadequate response to first-gen SSA) | Approved | A | PAOLA (Gadelha M, et al. Lancet Diabetes Endocrinol. 2014;2:875–84. PMID: 25260838) | Biochemical control at 24 wk: 15–20% pasireotide LAR vs 0% active control | Active comparator, not placebo |
Key studies
| Study | Design/population | Exposure studied | Endpoints and result | Limitations |
|---|---|---|---|---|
| CSOM230B2305 | Open-label, single-arm, N=162, Cushing's disease | SC pasireotide 600–900 mcg BID | UFC normalized in 15–26% at month 6 | Uncontrolled; high discontinuation (43%) |
| PAOLA | RCT, N=198, acromegaly uncontrolled on first-gen SSA | Pasireotide LAR 40–60 mg IM q4wk vs octreotide LAR 30 mg | Biochemical response 15–20% vs 0% (p<0.001) | No placebo; sponsor selection bias |
| CSOM230B2306 | Extension of B2305, Cushing's disease | Long-term pasireotide SC | Sustained UFC control in responders | Selected population |
Dose and administration evidence
Approved labeled regimen
The label summary below is product-, indication-, and jurisdiction-specific; consult the full current label and a licensed clinician/pharmacist.
Cushing's disease (Signifor SC): 0.6 mg SC BID initial, titrate to 0.9 mg SC BID based on tolerability and response. Acromegaly (Signifor LAR): 40 mg IM q4wk initial, maximum 60 mg. Cushing's disease (Signifor LAR): 10 mg IM q4wk initial, maximum 40 mg.
Studied regimens (not recommendations)
Phase 3 Cushing's: 0.6–0.9 mg SC BID.
PAOLA: pasireotide LAR 40–60 mg IM q4wk.
What is not established
Efficacy beyond 2 years in controlled settings.
Optimal sequencing after surgery or radiation.
No established or recommended human dose for unapproved indications.
Safety
Established label risks
Hyperglycemia: Very high rate (~73% in Cushing's phase 3). Diabetic ketoacidosis reported. Monitor glucose aggressively; antidiabetic therapy often required.
Gallbladder: Cholelithiasis (33% with LAR in acromegaly studies).
Cardiovascular: QT prolongation (caution/monitoring; not a contraindication per label); bradycardia.
Endocrine: Hypocortisolism (may require glucocorticoid replacement).
GI: Nausea, diarrhea, steatorrhea.
Hepatic: ALT/AST elevations.
Injection site: Pain, granuloma (LAR).
Human-study signals
Cushing's disease phase 3: hyperglycemia 73%; diabetes developed in 36%.
PAOLA: cholelithiasis 33% vs 14% octreotide; hyperglycemia 30%.
Unknowns and product-quality risks
Long-term cardiovascular outcomes with chronic hyperglycemia.
Research-grade material may not match Signifor formulation.
LAR microsphere preparation requires proper technique.
Interactions and special populations
The US labels list no contraindications. Coadministration with drugs that prolong QT may have additive effects and requires caution; baseline and on-treatment ECG/electrolyte monitoring is advised for at-risk patients.
Beta-blockers and CCBs for additive bradycardia.
Antidiabetic doses often need adjustment.
Cyclosporine levels may decrease; monitor.
Regulatory, compounding, and sport notes
WADA: Not prohibited.
Not scheduled under US CSA.
Hyperglycemia monitoring requirement distinguishes from first-gen SSA.
Evidence gaps
Glucose management strategy optimized for pasireotide-induced hyperglycemia.
Direct comparison to second-line agents for Cushing's disease.
Long-term tumor control data for pasireotide LAR in NETs (not approved).
Search notes
Databases and registries: DailyMed, PubMed, ClinicalTrials.gov, EMA EPAR
Search terms: pasireotide, Signifor, SOM230, Cushing's disease, acromegaly
Last searched: 2026-08-06
Inclusion emphasis: Regulatory labels, pivotal phase 3 trials, safety analyses
Sources
Signifor (pasireotide) prescribing information. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a09a25fc-a5a3-0c82-e053-2995a90a5d74
Signifor LAR (pasireotide) prescribing information. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0aad470-3f38-af97-e053-2995a90a383a
Colao A, et al. Pasireotide in Cushing's disease (NCT00434148). N Engl J Med. 2012;366(10):914–24. PMID: 22397653.
Gadelha MR, et al. Pasireotide vs octreotide in acromegaly (PAOLA). Lancet Diabetes Endocrinol. 2014;2(11):875–84. PMID: 25260838.
PubChem. Pasireotide. https://pubchem.ncbi.nlm.nih.gov/compound/9941444