Pasireotide
A somatostatin analogue that works where others fail, at the cost of raising blood sugar in most people who take it
Pasireotide binds four of the five somatostatin receptors rather than mainly one, which lets it work in Cushing's disease and in acromegaly uncontrolled by older analogues. The same breadth causes hyperglycaemia and diabetes in a large share of patients.
What is it?
Octreotide and lanreotide act mainly at one somatostatin receptor subtype. Pasireotide binds four, including SSTR5, which is the one that matters in corticotroph pituitary tumours. That is why it works in Cushing's disease, where the older analogues do not.
The label is for adults with Cushing's disease for whom pituitary surgery is not an option or has not cured them. Dosing starts at 0.6 or 0.9 mg subcutaneously twice a day within a 0.3 to 0.9 mg range, titrated on 24-hour urinary free cortisol and on tolerability. Before the first dose the label asks for fasting glucose, HbA1c, liver tests, an ECG, a gallbladder ultrasound and potassium and magnesium levels. In moderate liver impairment (Child-Pugh B) the starting dose is 0.3 mg twice daily with a 0.6 mg maximum, and it should be avoided in severe impairment.
The 12-month phase 3 trial that supported approval randomised 162 adults with Cushing's disease to 600 or 900 µg twice daily. Urinary free cortisol fell by about half by month 2 and stayed there, but the primary endpoint, a normal level, was reached by only 12 of 82 at the lower dose and 21 of 80 at the higher dose, more often in those whose baseline was no more than five times normal. Cortisol in serum and saliva, corticotropin and clinical signs also improved. A monthly long-acting form later tested in 150 patients reached its primary endpoint in about 41% at either 10 or 30 mg, and in an extension half of those who continued had normal urinary cortisol at their last assessment.
In acromegaly, the long-acting form was compared with octreotide in a head-to-head superiority trial: biochemical control was reached by 31.3% against 19.2%, and normal IGF-1 by 38.6% against 23.6%. In patients already inadequately controlled on octreotide or lanreotide, the PAOLA trial found 15% at 40 mg and 20% at 60 mg reached control at 24 weeks against none who continued their previous drug.
The cost of the broad receptor binding is metabolic, and the label does not bury it: hyperglycaemia and diabetes occur on initiation, with intensive glucose monitoring recommended and fasting glucose tested before dosing. Hypocortisolism, bradycardia and QT prolongation, liver test elevations, gallstones, pituitary hormone deficiency and fat malabsorption are all in the warnings. The size of the problem is consistent across trials: hyperglycaemia-related adverse events occurred in 118 of 162 patients in the Cushing's trial, in 57.3% on pasireotide against 21.7% on octreotide in acromegaly, and diabetes in 21% to 26% in PAOLA against 8% on continued treatment.
A dedicated healthy-volunteer study measured the glucose effect and what blunts it, which is unusual and useful: the rise was reduced most by a GLP-1 drug. In the same volunteer programme, pasireotide had a modest QT-prolonging effect at the therapeutic dose and slowed heart rate by 10 to 15 beats a minute. The label says to use it with caution alongside other QT-prolonging drugs, to monitor cyclosporine levels, and to consider lowering bromocriptine. Pasireotide peaks within 15 to 30 minutes of an injection and has an effective half-life of about 12 hours in healthy volunteers.
Mechanism of Action
Pasireotide is a somatostatin analogue that binds four receptor subtypes, including SSTR5 on corticotroph tumours.
SSTR5 binding
Reaches the receptor that matters in corticotroph pituitary tumours, which octreotide and lanreotide mostly miss.
Glucose effects
Blood glucose rises on starting, so the label requires testing and close monitoring; in volunteers the rise was blunted most by a GLP-1 drug.
Heart rate and QT
Slowed heart rate by 10 to 15 bpm with modest QT prolongation in healthy volunteers.
Published Research
The studies behind pasireotide, read from their PubMed abstracts: Cushing's disease trials of twice-daily and monthly forms, acromegaly comparisons, and the glucose and heart-rhythm studies.
The trial behind the approval
In 162 adults with Cushing's disease, the primary endpoint, normal urinary free cortisol, was reached by 12 of 82 on 600 µg and 21 of 80 on 900 µg twice daily; median levels fell about 50% by month 2, and hyperglycaemia-related events affected 118 patients.
Once-monthly pasireotide in Cushing's disease
In 150 patients, the primary endpoint was met by 41.9% on 10 mg and 40.8% on 30 mg; hyperglycaemia (about 48%), diarrhoea and gallstones (20% and 45%) were common.
Monthly form: extension to a median 24 months
Of 81 patients who entered the extension, 53.1% had normal mean urinary free cortisol at their last assessment; 51.9% discontinued, and hyperglycaemia-related events occurred in 39.5%.
Where older analogues had failed
In 198 patients inadequately controlled on octreotide or lanreotide, 15% on pasireotide 40 mg and 20% on 60 mg achieved biochemical control at 24 weeks against none on continued treatment; hyperglycaemia affected 33% and 31% against 14%.
Acromegaly: head-to-head with octreotide LAR
Biochemical control was 31.3% on pasireotide LAR against 19.2% on octreotide LAR, and normal IGF-1 38.6% against 23.6%; hyperglycaemia-related events 57.3% against 21.7%.
In acromegaly
After four weeks of pasireotide 200 to 600 mcg twice daily, 19% of patients with acromegaly achieved a biochemical response, rising to 27% at three months, and 39% had a reduction of more than 20% in pituitary tumour volume.
Measuring and blunting the glucose rise
In healthy volunteers, seven days of pasireotide raised the glucose area under the curve after an oral glucose load by 69%. Co-administration reduced that rise by 13% with metformin, 29% with nateglinide, 45% with vildagliptin and 72% with liraglutide.
Its effect on the heart's rhythm
In healthy volunteers, pasireotide 600 µg twice daily had a modest QT-prolonging effect, rising only about 3 ms more at 1,950 µg, and slowed heart rate by 10.4 and 14.9 bpm at the two doses.
Dosing Data
Signifor is injected under the skin twice daily and titrated on urinary free cortisol and tolerability.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Signifor label (SPL version 20, effective February 17, 2026) and the trials.
Contraindications & Cautions
From the label.
Legal Status
An approved specialist medicine.
Frequently Asked Questions
?How does pasireotide differ from octreotide?
It binds four somatostatin receptor subtypes rather than mainly one, including SSTR5, which is why it works in Cushing's disease where octreotide does not.
?Does it cause diabetes?
It raises blood sugar in a large share of patients: in the pivotal Cushing's trial, 74 of 162 had to start glucose-lowering medication.
?Can the glucose rise be managed?
A healthy-volunteer study measured a 69% rise in glucose exposure and found co-administration reduced it, most with liraglutide at 72%.
?What else does the label warn about?
Hypocortisolism, bradycardia and QT prolongation, liver test elevations, gallstones, pituitary hormone deficiency and fat malabsorption.
?How well does it control cortisol?
In the 12-month trial, urinary cortisol halved within two months, but only 12 of 82 on 600 µg and 21 of 80 on 900 µg reached a normal level; milder cases responded better.
?Is it better than octreotide for acromegaly?
In a head-to-head trial the long-acting form controlled 31.3% against 19.2%, at the cost of much more hyperglycaemia.
?What must be checked before starting?
Fasting glucose and HbA1c, liver tests, an ECG, a gallbladder ultrasound, and potassium and magnesium (label).
References
- [fda-pi] Signifor (pasireotide) prescribing information, sections 1, 2, 5 and 6 (DailyMed SPL version 20, effective February 17, 2026; read October 1, 2026).
- [pubmed] Colao A, et al. "A 12-month phase 3 study of pasireotide in Cushing's disease." N Engl J Med, 2012;366(10):914-24. PMID: 22397653.
- [pubmed] Lacroix A, et al. "Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial." Lancet Diabetes Endocrinol, 2018;6(1):17-26. PMID: 29032078.
- [pubmed] Fleseriu M, et al. "Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study." Clin Endocrinol (Oxf), 2019;91(6):776-785. PMID: 31465533.
- [pubmed] Gadelha MR, et al. "Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial." Lancet Diabetes Endocrinol, 2014;2(11):875-84. PMID: 25260838.
- [pubmed] Colao A, et al. "Pasireotide versus octreotide in acromegaly: a head-to-head superiority study." J Clin Endocrinol Metab, 2014;99(3):791-9. PMID: 24423324.
- [pubmed] Petersenn S, et al. "Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial." J Clin Endocrinol Metab, 2010;95(6):2781-9. PMID: 20410233.
- [pubmed] Breitschaft A, et al. "Management of hyperglycemia associated with pasireotide (SOM230): healthy volunteer study." Diabetes Res Clin Pract, 2014;103(3):458-65. PMID: 24461109.
- [pubmed] Breitschaft A, et al. "Effects of Subcutaneous Pasireotide on Cardiac Repolarization in Healthy Volunteers: a Single‐Center, Phase I, Randomized, Four‐Way Crossover Study." J Clin Pharmacol, 2014;54(1):75-86. PMID: 24242903.
Sources & Citations
Studies were read from their PubMed records (October 6, 2026); the label and Drugs@FDA are listed below with their read dates.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.