Pasireotide

Signifor (short-acting), Signifor LAR (depot), SOM230, pasireotide diaspartate / pasireotide pamoate

Sexual health, hormones & signalling

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Pasireotide is an approved prescription medicine for Cushing's disease and acromegaly, not a research-only compound. This page explains the published science. Community/self-directed use is essentially none documented. It is notable among peptides for causing high blood sugar in most people who take it.

Summary

Class: Synthetic cyclic hexapeptide (6 amino acids, including unnatural residues) — a second-generation, multi-receptor somatostatin analogue
Mechanism: Activates four of the five somatostatin receptors (SSTR1, 2, 3 and especially SSTR5) to suppress ACTH from pituitary corticotroph tumours and GH from somatotroph tumours that respond poorly to octreotide or lanreotide
Routes studied: Subcutaneous injection twice daily (Signifor); intramuscular depot every 4 weeks (Signifor LAR)
Half-life: ~12 h after subcutaneous injection (allowing twice-daily dosing); LAR releases over ~4 weeks with steady state after ~3 injections
Storage: Ampoules: room temperature (below 25 °C), protect from light. LAR kit: refrigerate 2–8 °C, bring to room temperature 30 min before mixing
Regulatory status: Approved medicine (EU 2012, US Dec 2012 for Cushing's disease; LAR for acromegaly US Dec 2014 and EU 2014; LAR for Cushing's EU 2017, US 2018). Now marketed by Recordati Rare Diseases

Doses are as reported in studies or by the community — never recommendations.

1What it is

Pasireotide was designed by Novartis in the 2000s to fix a limitation of octreotide and lanreotide: those two bind mainly SSTR2, and some pituitary tumours — especially the ACTH-secreting tumours of Cushing's disease and a subset of GH-secreting tumours — express more SSTR5 than SSTR2. Pasireotide binds SSTR5 roughly 40 times more tightly than octreotide does, while keeping SSTR2 and adding SSTR1 and SSTR3. It is a ring of six amino acids, smaller than octreotide's eight.

It was the first drug approved anywhere that targets the pituitary tumour itself in Cushing's disease (2012), and a second-line option in acromegaly for patients not controlled on first-generation analogues. Its broader receptor profile has a cost: by activating SSTR5 on pancreatic beta cells and gut L-cells it suppresses insulin and the incretin hormones GLP-1 and GIP, and most patients develop raised blood sugar.

2How it's thought to work

Binding affinities (nanomolar): SSTR5 > SSTR2 ≈ SSTR3 > SSTR1; essentially no SSTR4 activity (Bruns 2002, Eur J Endocrinol).

In corticotroph adenomas, SSTR5 activation reduces ACTH synthesis and release, lowering cortisol; octreotide fails here partly because high cortisol down-regulates SSTR2 but not SSTR5.

In somatotroph adenomas, dual SSTR2/SSTR5 activation suppresses GH in tumours with low SSTR2 density, and lowers IGF-1.

Direct anti-proliferative effects shrink tumours in a proportion of patients.

Hyperglycaemia arises mainly from suppressed insulin and incretin secretion; insulin sensitivity is relatively preserved, which is why GLP-1-based drugs and DPP-4 inhibitors are the preferred countermeasures.

A somatostatin analogue that binds SSTR5 most strongly rather than SSTR2. That is why it lowers ACTH in Cushing's disease where octreotide does not — the two receptor shapes in the figure are the whole difference.Schematic — not to scale

3What the research shows

Cushing's disease

A phase 3 trial (n=162) of 0.6 or 0.9 mg twice daily found normal urinary free cortisol at 6 months in 15% and 26% respectively, with cortisol falls in most patients and improvements in blood pressure, weight and quality of life; hyperglycaemia-related adverse events occurred in 73% (Colao 2012, NEJM). A phase 3 LAR trial (n=150) found 41% of patients normalised cortisol at 7 months on 10 or 30 mg monthly (Lacroix 2018, Lancet Diabetes Endocrinol). [2][3]

Acromegaly, first-line

C2305 (n=358) compared pasireotide LAR 40 mg with octreotide LAR 20 mg in medically naive patients: biochemical control 31.3% vs 19.2% at 12 months (Colao 2014, J Clin Endocrinol Metab). [4]

Acromegaly inadequately controlled on first-generation analogues

PAOLA (n=198) randomised patients to pasireotide LAR 40 or 60 mg or to continued octreotide/lanreotide: control at 24 weeks in 15% and 20% vs 0% (Gadelha 2014, Lancet Diabetes Endocrinol). This is the basis of its second-line positioning. [5]

Graded A/B (mixed)

Neuroendocrine tumours, carcinoid syndrome, dumping syndrome, post-operative pancreatic fistula

Pasireotide did not beat octreotide for refractory carcinoid symptoms; a single-centre found it reduced post-pancreatectomy fistulas (Allen 2014, NEJM) but later studies were inconsistent. Not approved for these uses. [7]

4Reported side effects and interactions

Literature-reported

hyperglycaemia is the defining adverse effect — raised glucose in roughly 57–73% of patients and new diabetes in about a quarter to a third, typically emerging within the first 3 months. Also diarrhoea, nausea, abdominal pain, gallstones (~20–30%), fatigue, headache, injection-site reactions, hair loss, bradycardia and QT prolongation (ECG monitoring recommended), raised liver enzymes, and in Cushing's disease the risk of over-correction to cortisol deficiency (hypocortisolism) as the tumour responds. Hypothyroidism and reduced B12 as with other analogues.

Community-reported

none documented.

Theoretical. in anyone without a pituitary tumour the drug would be expected to raise glucose and suppress GH and insulin with no upside.

Interactions. QT-prolonging drugs and antiarrhythmics; beta-blockers and calcium-channel blockers (bradycardia); cyclosporine (reduced absorption); bromocriptine (increased levels); insulin and antidiabetics (dose adjustments, usually upward); in Cushing's disease, glucocorticoid replacement may become necessary.

Markers researchers commonly monitor

Per label, with emphasis on glucose:

Marker	Why it's watched
Fasting glucose and HbA1c	before starting, weekly for the first 3 months (label advice), then regularly; the single most important monitoring item.
Urinary free cortisol (24-hour), late-night salivary cortisol, morning serum cortisol	response in Cushing's disease and detection of over-suppression (hypocortisolism).
IGF-1 and GH	response in acromegaly.
ECG (QTc) and heart rate	at baseline and after dose changes; correct potassium and magnesium first.
Liver enzymes	baseline, then at 2–3 weeks and periodically.
Gallbladder ultrasound	baseline and every 6–12 months.
TSH/free T4, vitamin B12	periodically.
Pituitary MRI	tumour size tracking in both indications.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Short-acting Signifor is a ready-to-use solution in single-dose ampoules (0.3, 0.6, 0.9 mg/mL) for self-injection into thigh or abdomen. Signifor LAR is a microsphere powder that must be suspended with the supplied immediately before deep (gluteal) injection by a healthcare professional. The calculator is not applicable.

6Commonly studied alongside

Octreotide (profile 124) and lanreotide (profile 125), the first-generation comparators; cabergoline and ketoconazole, metyrapone or osilodrostat in Cushing's disease; pegvisomant in acromegaly. Metformin, DPP-4 inhibitors and GLP-1 receptor agonists are the studied countermeasures for pasireotide hyperglycaemia (Samson 2021, J Clin Endocrinol Metab).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved: Signifor SC for Cushing's disease when surgery is not an option or has failed (Dec 2012); Signifor LAR for acromegaly (Dec 2014) and Cushing's disease (2018)
European Union	EMA-authorised: Signifor (2012, Cushing's disease); Signifor LAR for acromegaly (2014) and Cushing's disease (2017)
United Kingdom	MHRA-licensed; prescription-only, specialist endocrine use
Australia	TGA-registered for Cushing's disease and acromegaly †
South Africa	Registration status †
Sport	Not on the WADA Prohibited List

8Open questions

Whether receptor-expression profiling before treatment can predict who will respond and who will mainly get hyperglycaemia.
The best strategy for pasireotide-induced hyperglycaemia and whether it reverses fully after stopping.
Long-term cardiovascular safety given the QT and bradycardia effects in patients who already have Cushing's-related cardiovascular risk.

9References

1Bruns C et al. (2002). SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. PubMed · DOI
2Colao A et al. (2012). A 12-month phase 3 study of pasireotide in Cushing's disease. NEJM. PubMed · DOI
3Lacroix A et al. (2018). Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial. Lancet Diabetes Endocrinol. PubMed · DOI
4Colao A et al. (2014). Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. PubMed · DOI
5Gadelha MR et al. (2014). Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA). Lancet Diabetes Endocrinol. PubMed · DOI
6Henry RR et al. (2013). Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J Clin Endocrinol Metab. PubMed · DOI
7Allen PJ et al. (2014). Pasireotide for postoperative pancreatic fistula. NEJM. PubMed · DOI
8Recordati Rare Diseases. Signifor and Signifor LAR prescribing information (current labels). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

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