reviewed april 2026|next review october 2026|88 physicians psi has verified|81454 published studies
Pasireotide (SOM230)
Pasireotide is a cyclohexapeptide somatostatin analog FDA-approved as Signifor for Cushing's disease (2012) and as Signifor LAR for acromegaly (2014), with 40-fold greater affinity for the SST5 somatostatin receptor subtype than first-generation analogs.
Evidence landscape: 81454 published studies
81,454 published items (inflated by broad somatostatin query). 25 human studies and 125 animal studies indexed. A focused clinical evidence base supporting two rare-disease FDA approvals.
- 25 Human
- 125 Animal
- 50 Reviews
- 81254 Other research
FDA-approved prescription medicine: Signifor (2012) for Cushing's disease, Signifor LAR (2014) for acromegaly inadequately controlled by first-generation somatostatin analogs.
Phase III trials for both indications. Approximately 26% cortisol normalization in Cushing's disease. Superior biochemical control in acromegaly versus first-generation analogs.
Multi-receptor somatostatin analog with broader SST coverage than octreotide or lanreotide. The 40-fold greater SST5 affinity specifically targets corticotroph adenomas. Major trade-off: hyperglycemia in approximately 75% of patients.
PSI Assessment
When a pituitary tumor produces too much cortisol or growth hormone, and the standard somatostatin analog does not control it, pasireotide is the next step. Sold as Signifor, it is FDA-approved for Cushing's disease and acromegaly, two rare conditions caused by hormone-secreting pituitary tumors. It binds a broader range of somatostatin receptor subtypes than octreotide, with 40-fold greater affinity for the SST5 receptor predominant on corticotroph adenomas. The clinical trade-off is significant: approximately 75% of patients develop hyperglycemia.
40-fold greater SST5 affinity than octreotide. Reaches the tumor cells that first-generation somatostatin analogs miss. The trade-off: hyperglycemia in 75% of patients.
The mechanism is somatostatin receptor agonism across five receptor subtypes (SST1-5), with particularly high SST5 affinity. Corticotroph adenomas in Cushing's disease express SST5 as their predominant somatostatin receptor, which is why first-generation analogs (octreotide, lanreotide) that primarily target SST2 often fail to control ACTH (adrenocorticotropic hormone) secretion. Pasireotide's broader receptor coverage reaches the tumor cells that SST2-selective drugs miss.
What the evidence supports
FDA-approved for both Cushing's disease and acromegaly with Phase III data for each indication. The broader somatostatin receptor profile (particularly 40-fold greater SST5 affinity) represents a genuine pharmacological advance over first-generation analogs. Effective in patients who fail octreotide or lanreotide, reaching tumor cells that SST2-selective drugs miss.
What is not yet established
Superiority to other Cushing's disease treatments (osilodrostat, mifepristone) in head-to-head comparisons. Optimal management strategies for the substantial hyperglycemia risk affecting approximately 75% of patients. Whether pasireotide should be first-line or reserved for patients failing other therapies.
Research Evidence
The findings below cover the Phase III evidence for both approved indications and the hyperglycemia trade-off.
Evidence by condition
Evidence dimensions across pasireotide indications. Both Cushing's disease and acromegaly have deep clinical evidence supporting FDA approval, with the hyperglycemia trade-off well-characterized across both programs.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Cushing's Disease | ||||
| Acromegaly |
The Phase III Cushing's disease trial demonstrated urinary free cortisol normalization in approximately 26% of patients at 6 months. The SST5-targeting mechanism is the pharmacological basis: corticotroph adenomas express SST5 as their predominant somatostatin receptor subtype.
A 26% normalization rate reflects the difficulty of the condition, not a weak drug effect. Cushing's disease involves ACTH-secreting pituitary adenomas that are resistant to most medical therapies. Additional patients showed meaningful cortisol reduction without full normalization.
In acromegaly, pasireotide LAR (long-acting release) achieved superior biochemical control (GH and IGF-1 normalization) compared to octreotide LAR in patients with inadequate response to first-generation somatostatin analogs.
The PAOLA trial established pasireotide as a second-line option for acromegaly, specifically for patients who do not achieve adequate control with octreotide or lanreotide. The broader receptor binding profile is the mechanistic basis for this superiority.
Hyperglycemia occurred in approximately 75% of Cushing's disease trial participants. Nearly half of patients without baseline diabetes reached diabetic HbA1c thresholds during treatment. This is the primary safety trade-off that limits broader use.
The hyperglycemia is likely mediated by pasireotide's suppression of insulin and incretin secretion via somatostatin receptor activation on pancreatic beta cells. Proactive glucose monitoring and anti-diabetic therapy are required during treatment.
25 Human|125 Animal|50 Reviews
View all 81454 indexed studiesHow Pasireotide (SOM230) Works
Pasireotide is a cyclohexapeptide somatostatin analog that binds somatostatin receptors SST1, SST2, SST3, and SST5. The 40-fold greater SST5 affinity compared to octreotide is the key differentiator, enabling inhibition of ACTH secretion from corticotroph adenomas and GH secretion from somatotroph adenomas.
Certain pituitary tumors produce too much cortisol (Cushing's disease) or growth hormone (acromegaly). Pasireotide mimics somatostatin. A natural hormone that tells these cells to stop producing hormones. By binding more receptor subtypes than older drugs, it can shut down tumors that did not respond to previous treatments.
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
Pasireotide binds somatostatin receptors SST1-5 with high affinity for SST5 (40x greater than octreotide). SST5 is the predominant receptor on corticotroph adenomas. It inhibits ACTH secretion in Cushing's disease and GH/IGF-1 in acromegaly.
What is Pasireotide (SOM230) being studied for?
Researchers are studying Pasireotide (SOM230) across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for Pasireotide (SOM230) overall. This means a compound can have human studies for one condition but only animal data for another.
Cushing's Disease
·FDA ApprovedFDA-approved for Cushing's disease in patients who are not candidates for surgery or for whom surgery has failed. Reduces cortisol production by targeting ACTH-secreting pituitary tumors via SST5 receptor agonism.
Limitations: Hyperglycemia occurs in approximately 75% of patients. Nearly half without baseline diabetes develop diabetic HbA1c levels. Blood sugar monitoring and management are essential.
Acromegaly
·FDA ApprovedFDA-approved long-acting formulation (Signifor LAR) for acromegaly in patients with inadequate response to first-generation somatostatin analogs (octreotide, lanreotide). Achieves GH and IGF-1 control through broader receptor binding.
Limitations: Hyperglycemia is more common than with octreotide. Reserved for patients who fail first-line somatostatin analogs rather than used as initial therapy.
Safety and Regulatory Status
FDA Status: FDA-approved: Signifor (2012) for Cushing's disease, Signifor LAR (2014) for acromegaly inadequately controlled by other somatostatin analogs.
Prescription status: Prescription-only in the United States. Specialist-administered for rare endocrine conditions.
Class context: Multi-receptor somatostatin analog. Octreotide and lanreotide are first-generation SST2-selective analogs. Pasireotide adds broader SST coverage at the cost of higher hyperglycemia rates.
Hyperglycemia is the most significant safety concern, affecting approximately 75% of Cushing's disease patients. Blood sugar monitoring is mandatory during treatment. Other side effects include GI symptoms (diarrhea, nausea), gallstones, and bradycardia, consistent with the somatostatin analog class.
Peptide Structure
Technical molecular data for researchers and clinicians.
Questions and Comparisons
Questions the evidence raises for a Pasireotide (SOM230) discussion.
Comparison and Related Research
Pasireotide is most often compared with first-generation somatostatin analogs (octreotide, lanreotide) which it is designed to improve upon for treatment-resistant cases.
Related compounds
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.Pivotal Phase III trial in patients with Cushing's disease. Pasireotide significantly reduced urinary free cortisol levels - the key marker of excess cortisol production - in a majority of patients over 12 months. This study formed the basis for the first FDA-approved medical treatment specifically for Cushing's disease.Colao A et al., 2012 in N Engl J Med. View on PubMed
- 2.Phase III PAOLA trial testing pasireotide long-acting release against continued octreotide or lanreotide in patients with acromegaly not adequately controlled by first-generation somatostatin analogues. Pasireotide achieved biochemical control in a significantly higher proportion of patients.Gadelha MR et al., 2014 in Lancet Diabetes Endocrinol. View on PubMed
- 3.Phase III trial of the long-acting monthly formulation in Cushing's disease. Demonstrated that a once-monthly injection could effectively reduce cortisol levels, offering a more convenient dosing schedule compared to the twice-daily subcutaneous injections used in the original approval.Lacroix A et al., 2018 in Lancet Diabetes Endocrinol. View on PubMed
- 4.Phase II proof-of-concept trial that first demonstrated pasireotide could reduce cortisol levels in patients with Cushing's disease. Provided the clinical rationale for proceeding to the larger Phase III program.Boscaro M et al., 2009 in J Clin Endocrinol Metab. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.