Signifor / Signifor LAR (pasireotide)
Pasireotide diaspartate (subcutaneous form); Pasireotide pamoate (long-acting release intramuscular form). Synonyms: SOM230, SOM230C. Chemical name: (2-Aminoethyl) carbamic acid (2R,5S,8S,11S,14R,17S,19aS)-11-(4-aminobutyl)-5-benzyl-8-(4-benzyloxybenzyl)-14-(1H-indol-3-ylmethyl)-4,7,10,13,16,19-hexaoxo-17-phenyloctadecahydro-3a,6,9,12,15,18-hexaazacyclopentacyclooctadecen-2-yl ester, di[(S)-2-aminosuccinic acid] salt (diaspartate form).
Pasireotide (Signifor) is an FDA-approved injectable cyclohexapeptide somatostatin analog with high affinity for SSTR5, indicated for Cushing's disease and acromegaly; it was the first pituitary-directed medical therapy for Cushing's disease.
Last updated: 2026-03-13
Safety Summary
The safety profile of pasireotide is dominated by metabolic effects, particularly hyperglycemia. In the pivotal Phase III Cushing's disease trial (N=162), nearly all patients experienced worsening glycemia within the first 2 weeks of treatment, including those with normal glucose status at baseline. Mean FPG increased from 98.6 to 125.1 mg/dL (0.6 mg group) and 97.0 to 128.0 mg/dL (0.9 mg group) at month 6. HbA1c rose from 5.8% to 7.2-7.3%. The hyperglycemia mechanism is related to SSTR5-mediated suppression of insulin secretion and incretin hormones (GLP-1, GIP), which was demonstrated in a dedicated mechanism study in healthy volunteers (. Patients with HbA1c >8% at baseline are at higher risk for severe hyperglycemia including ketoacidosis (. For the LAR formulation in acromegaly, the prevalence of diabetes increased from 30% at baseline to 60% at 12 months in drug-naive patients (. Gastrointestinal effects (diarrhea, nausea) typically begin in the first month and resolve without intervention. Cholelithiasis rates of 26-33% across studies necessitate periodic gallbladder ultrasound monitoring. Transient liver enzyme elevations occurred in the first weeks, with 4 cases of concurrent ALT >3x ULN and bilirubin >2x ULN observed across the clinical development program (1 Cushing's patient, 3 healthy volunteers), all resolving upon discontinuation (. QT prolongation is dose-dependent with a maximum mean QTcI change of 12.7 ms at therapeutic dose (0.6 mg BID) and 16.6 ms at supra-therapeutic dose (1.95 mg BID), accompanied by dose-dependent bradycardia (. Serious adverse events were reported in 25% of patients in the pivotal trial; 17% discontinued due to adverse events. No deaths occurred during the study (. The Signifor LAR label added a steatorrhea/malabsorption warning in July 2024 (.
Known Side Effects
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Who Should NOT Use This
The FDA label Section 4 states 'None' for contraindications for both Signifor and Signifor LAR. However, severe hepatic impairment (Child-Pugh C) is listed as 'avoid use' under dosage and administration (.
Use should be avoided in patients with Child-Pugh C hepatic impairment due to significantly higher drug exposure (AUC increased 42%) and limited safety data. Moderate impairment (Child-Pugh B) requires dose reduction (.
Patients with poor glycemic control are at higher risk for severe hyperglycemia and complications including ketoacidosis. Anti-diabetic therapy should be optimized before starting pasireotide (.1/5.2).
Pasireotide causes QT prolongation (max mean QTcI change 12.7 ms at 0.6 mg BID) and bradycardia. Use with caution in patients with congenital long QT, recent myocardial infarction, congestive heart failure, unstable angina, or clinically significant bradycardia (.3).
Coadministration of drugs that prolong QT with pasireotide may have additive effects on QT prolongation (.1).
Must be corrected prior to initiating pasireotide and monitored periodically during therapy, as they increase risk of QT prolongation (.3).
Limited data in pregnant women. Animal studies showed developmental delay in rabbits at sub-therapeutic exposures and increased resorptions/limb malrotations in rats at high doses. Premenopausal women should be counseled on potential for unintended pregnancy as cortisol normalization may restore fertility (.1 and 8.3).
Pasireotide may decrease the bioavailability of cyclosporine; dose adjustment of cyclosporine may be necessary to maintain therapeutic levels (.2).
Somatostatin analogs may increase blood levels of bromocriptine; dose reduction of bromocriptine may be necessary (.2).
Talk to Your Doctor
Before considering Signifor / Signifor LAR (pasireotide), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-10]
Evidence Assessment
Pasireotide is FDA-approved with two distinct NDA approvals: NDA200677 (Signifor SC, approved December 2012 for Cushing's disease) and NDA203255 (Signifor LAR, approved December 2014 for acromegaly; subsequently also approved for Cushing's disease). Both approvals were supported by Phase III randomized controlled trials. The drug also has EMA and TGA approvals and orphan drug designations.
1A 12-month phase 3 study of pasireotide in Cushing's diseaseNCT00434148PMID 22397653
Colao A, Petersenn S, Newell-Price J, et al. - New England Journal of Medicine (2012) - Phase III randomized controlled trial - 162 patients
15% (0.6 mg BID) and 26% (0.9 mg BID) achieved UFC normalization at 6 months. Median UFC reductions of 47% and 46%. Hyperglycemia in 40%, diarrhea 58%, nausea 52%, cholelithiasis 30%.
Limitations: No placebo control group (compared two active doses). Open-label design after month 3. Limited to patients with persistent/recurrent Cushing's disease. Short-term primary endpoint at 6 months.
2Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III studyPMID 24533697
Pivonello R, et al. - Clinical Endocrinology (2014) - Phase III secondary endpoint analysis - 162 patients (same pivotal trial)
Significant improvements in clinical signs and symptoms of Cushing's disease including blood pressure reduction, weight loss (mean 4.4 kg), BMI decrease (1.6 kg/m2), and waist circumference reduction (2.6 cm) at 6 months.
Limitations: Secondary/exploratory endpoints from the same Phase III trial without a control group. Changes in clinical signs may not be entirely attributable to pasireotide given concurrent medication adjustments.
3Pasireotide treatment significantly reduces tumor volume in patients with Cushing's disease: results from a Phase 3 study
Not specified in raw data - Pituitary (2020) - Phase III secondary endpoint analysis - 162 patients (same pivotal trial)
Tumor volume reduction of 20-27% observed in patients with measurable pituitary tumors, providing evidence for antiproliferative effect of pasireotide in Cushing's disease.
Limitations: Not all patients had measurable tumors. Retrospective analysis of tumor volume from the pivotal trial.
4Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study
Bronstein MD, Freda P, et al. - BMC Endocrine Disorders (2016) - Phase III crossover extension - Subset of C2402 study participants
Patients switched from octreotide LAR to pasireotide LAR showed improved biochemical control. 17% achieved full biochemical control (GH and IGF-1 normalization) after switching.
Limitations: Open-label crossover design. Selection bias from patients willing to switch. Limited sample in the extension.
5Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analoguesPMID 26366058
Wolin EM, et al. - Oncologist (2015) - Phase III clinical trial - Not specified in raw data
Evaluation of pasireotide LAR in metastatic NETs with refractory carcinoid symptoms.
Limitations: Refractory population with limited treatment options. Specific findings not fully extractable from available raw data.
6Pasireotide -- a novel somatostatin receptor ligand after 20 years of use
Jawiarczyk-Przybylowska A, et al. - Reviews in Endocrine and Metabolic Disorders (2022) - Comprehensive review - N/A (review article)
Comprehensive 20-year review of pasireotide efficacy and safety across indications. Confirmed role as second-line therapy in acromegaly and first-line medical therapy for Cushing's disease. Hyperglycemia remains the major limiting adverse effect.
Limitations: Narrative review without systematic methodology.
7Pasireotide Treatment for Patients With Prolactinomas Who Need Treatment Beyond Dopamine Agonist TherapyNCT06295952
Geer E (PI), Memorial Sloan Kettering Cancer Center - ClinicalTrials.gov (2024) - Phase II open-label pilot (recruiting) - 10 estimated
Active recruiting study evaluating pasireotide LAR (40-60 mg q4w) for dopamine agonist-resistant or intolerant prolactinoma patients. Primary endpoint: prolactin normalization at 24 weeks.
Limitations: Small pilot study (n=10). Single-arm, no comparator. Currently recruiting, no results yet.
8Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Pasireotide LAR in Patients With Castration Resistant Prostate CancerNCT01646684
Novartis Pharmaceuticals - ClinicalTrials.gov (2013) - Phase I dose escalation (completed) - 9 patients
Defined maximum tolerated dose of pasireotide LAR in CRPC. Very small study.
Limitations: Only 9 patients enrolled. Phase I safety-only design. No efficacy signal reported in raw data. Single-arm.
9Consensus on diagnosis and management of Cushing's disease: a guideline updatePMID 34687601
Fleseriu M, Auchus R, Bancos I, et al. - Lancet Diabetes & Endocrinology (2021) - Consensus guideline / expert review - N/A
International consensus positioning pasireotide as a medical therapy option for Cushing's disease, particularly as first-line pituitary-directed therapy when surgery is not feasible or has failed.
Limitations: Expert consensus rather than original research. May reflect opinion bias.
10Real-life data on pasireotide in monotherapy or combined in active Cushing's disease
Not specified in raw data - Frontiers in Endocrinology (2025) - Real-world observational study - Not specified in raw data
Real-life experience with pasireotide monotherapy and combination therapy in active Cushing's disease. UFC normalization reported at 59% (LNSC at 38%) in the available summary data.
Limitations: Real-world retrospective data with inherent selection and reporting biases. Full text details not available in raw data.