Mechanism
Lanreotide is a synthetic 8-amino-acid cyclic somatostatin analog with structural similarity to octreotide. It binds preferentially to SSTR2 and SSTR5, with similar receptor selectivity to octreotide.
The distinguishing pharmaceutical feature is the Autogel formulation — a supersaturated aqueous solution that forms a depot at the injection site, releasing lanreotide over ~28 days. This is administered as a deep subcutaneous injection rather than intramuscular (octreotide LAR is IM with microsphere encapsulation). The deep-SC route is sometimes more convenient for self-administration or caregiver-administration in long-term NET management, though most patients still receive injections in clinic.
The receptor-pharmacology effects mirror octreotide: GH suppression (acromegaly), suppression of multiple GI hormones (GEP-NETs), and antiproliferative signaling through SSTR2 in tumor cells.
What the evidence shows
Phase 3 CLARINET (Caplin et al, NEJM 2014): Multi-center, double-blind, placebo-controlled trial in 204 patients with metastatic GEP-NETs (grade 1 or grade 2 with Ki-67 ≤10%). Lanreotide Autogel 120 mg every 28 days vs placebo.
Results at 96 weeks:
– Progression-free survival: not reached (lanreotide) vs 18 months (placebo); hazard ratio 0.47
– Statistically significant antiproliferative effect, independent of tumor functionality
This was a landmark trial — established somatostatin analogs as more than symptom-control drugs in NETs.
Acromegaly: Multiple RCTs and real-world studies show lanreotide Autogel achieves biochemical control (normal IGF-1) in roughly 40–60% of patients, comparable to octreotide LAR. Trial-level head-to-head comparisons show similar efficacy.
Functional NETs (carcinoid syndrome): Symptom control comparable to octreotide LAR.
The trial-level evidence positions lanreotide as a peer of octreotide rather than a successor — both are first-line, choice driven by clinical/practical factors.
Dosing literature
Approved dosing (deep subcutaneous, every 28 days):
- Acromegaly: 60 mg, 90 mg, or 120 mg every 28 days; titrate based on IGF-1 response
- GEP-NETs: 120 mg every 28 days (maximum dose used in CLARINET)
- Self-administration approved after caregiver/patient training
Pre-filled syringe; deep subcutaneous injection in the upper outer quadrant of the buttock (alternating sides). Self-injection is rare in practice but supported by the formulation.
Risks and adverse events
Common (class effect with somatostatin analogs):
- Diarrhea, abdominal cramping, steatorrhea — often improves over weeks but can be persistent
- Cholelithiasis (gallstones) — significant rate with long-term use
- Hyperglycemia or hypoglycemia (depending on individual response to somatostatin’s effects on insulin and glucagon)
- Injection site reactions
- Bradycardia, mild
Less common:
- Cholecystitis or pancreatitis (rare but possible with chronic use)
- Hypothyroidism with very-long-term high-dose use
- Vitamin B12 deficiency
The chronic-use safety profile is well-characterized; for most patients, the benefit of disease control or NET progression delay outweighs the GI burden.
Regulatory status
| Region | Status | Notes |
|---|---|---|
| United States | Approved (Somatuline Depot) | For acromegaly and GEP-NETs. |
| European Union | Approved (Somatuline Autogel) | Same indications. |
| United Kingdom | Approved | NHS access for the approved indications. |
| Japan | Approved | |
| Most major markets | Approved |
Manufacturer: Ipsen Pharma. Generic versions of the Autogel formulation are not yet widely available; the depot manufacturing complexity has limited generic entry.
Where to get it
Through endocrinology (acromegaly) or oncology (NETs) practice and a specialty pharmacy. The deep-SC injection technique is taught to patients or caregivers; many patients still receive in-clinic administration.
We have no fulfillment partner for lanreotide. (See How we make money.)
References (selected)
- Caplin ME et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014 (CLARINET). PubMed
- Caron PJ et al. Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly. J Clin Endocrinol Metab 2014.
- Pavel M et al. ENETS Consensus Guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 2016.
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Quick Facts
| Also Known As | Somatuline, BIM 23014, Lanreotide acetate |
|---|---|
| Sequence | D-βNal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH₂ (cyclic disulfide bridge between Cys2 and Cys7) |
| Molecular Formula | C54H69N11O10S2 |
| Molecular Weight | 1096.3 Da |
| PubChem CID | 6918011 |
Research Parameters
| Half-Life | ~23-30 days (for the prolonged-release depot formulation) |
|---|---|
| Stability | Lyophilized powder: Stable for the duration of the shelf life when stored as directed. Reconstituted solution (for immediate-use formulations): Use immediately. Pre-filled syringe depot formulation (Autogel): Stable unrefrigerated for up to 2 weeks prior to use. |
| Solubility | The commercial prolonged-release formulation (Somatuline Autogel/Depot) is a ready-to-use, aqueous solution. For research-grade lyophilized peptide, bacteriostatic water or sterile water for injection is typically used for reconstitution of immediate-release formulations. |
| Storage (Lyophilized) | For research-grade material: Store at -20°C, protect from light and moisture. |
| Storage (Reconstituted) | For research-grade immediate-release formulations: Store at 2-8°C and use within 24 hours, or as per specific study protocol. The commercial depot formulation is stored refrigerated (2-8°C) but can be kept at room temperature (below 25°C) for up to 2 weeks prior to administration. |
| Typical Research Dose | Not applicable in mcg for clinical use; the therapeutic depot dose is in mg (e.g., 60-120 mg). Research using non-depot forms is limited. |
| Cycle Parameters | In clinical research: Deep subcutaneous injection every 28 days, indefinitely for chronic conditions like acromegaly and NETs. Dose and interval are adjusted based on biochemical and clinical response. |
| Amino Acid Count | 11 |
Mechanism of Action
Lanreotide exerts its effects primarily by binding with high affinity to somatostatin receptors (SSTRs), particularly subtypes 2 and 5. This binding activates inhibitory G-proteins (Gi/o), leading to a cascade of intracellular events that suppress hormone secretion and cell proliferation.
Inhibition of Hormone Secretion: Binding to SSTRs on pituitary somatotroph cells and neuroendocrine tumor cells inhibits adenylate cyclase, reducing intracellular cyclic AMP (cAMP) levels. This decrease in cAMP leads to reduced calcium influx and inhibition of exocytosis, effectively suppressing the secretion of hormones like growth hormone (GH), insulin-like growth factor 1 (IGF-1), gastrin, insulin, glucagon, and vasoactive intestinal peptide (VIP).
Antiproliferative Effects: Through SSTR-mediated activation of protein tyrosine phosphatases (PTPs), lanreotide induces dephosphorylation of growth factor receptors and signaling proteins. It also promotes apoptosis via p53-dependent and independent pathways and can inhibit angiogenesis by reducing the secretion of vascular endothelial growth factor (VEGF).
Inhibition of Gastrointestinal Motility and Secretion: By binding to SSTRs in the gastrointestinal tract and pancreas, lanreotide reduces intestinal fluid secretion, pancreatic exocrine secretion, and splanchnic blood flow, which is beneficial in managing symptoms of carcinoid syndrome and pancreatic fistulas.
Research Applications
Acromegaly: Lanreotide is a first-line medical therapy for acromegaly. It effectively normalizes GH and IGF-1 levels in a majority of patients, reduces tumor volume in a subset, and alleviates clinical symptoms such as headache, arthralgia, and soft tissue swelling. Its long-acting formulation is a key advantage for chronic management.
Neuroendocrine Tumors (NETs): Lanreotide is approved for the treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). It provides effective control of hormone-related symptoms (e.g., flushing, diarrhea in carcinoid syndrome) and has been shown to significantly prolong progression-free survival, demonstrating both antisecretory and antitumor efficacy.
Thyroid Eye Disease (TED): Research has investigated lanreotide for moderate-to-severe TED due to the expression of SSTRs on orbital fibroblasts. Studies suggest it can reduce proptosis, soft tissue inflammation, and disease activity, potentially by inhibiting IGF-1 receptor cross-talk and local inflammatory responses.
Other Research Applications: Investigational uses include the treatment of pancreatic and enterocutaneous fistulas (by reducing secretory output), symptomatic management of polycystic liver disease associated with autosomal dominant polycystic kidney disease (ADPKD), and as an adjunct therapy in certain refractory diarrheal states.
Safety & Side Effects
The safety profile is well-characterized from extensive clinical use. Common side effects are mostly related to its pharmacological action on the gastrointestinal tract and include diarrhea, abdominal pain, nausea, flatulence, and steatorrhea. Injection site reactions (pain, nodules) are frequent but usually mild. Gallbladder abnormalities, such as sludge or asymptomatic gallstones, occur in a significant proportion of patients due to inhibition of gallbladder contractility and bile secretion. Hypoglycemia or hyperglycemia may occur due to altered insulin and glucagon secretion. Bradycardia and conduction abnormalities are rare but possible. Anecdotal reports include alopecia and fatigue. Theoretical concerns exist regarding the potential for nutrient malabsorption with long-term use due to pancreatic exocrine inhibition.
Dosage Information
Disclaimer: The following information is derived from published clinical research and is for educational purposes only.
In clinical research for acromegaly and NETs, lanreotide is administered as a deep subcutaneous injection of a prolonged-release formulation (Autogel/Depot). The typical dose is 60 mg, 90 mg, or 120 mg injected every 28 days. Dose titration is based on biochemical response (GH and IGF-1 levels) and symptom control. For some NET patients, the interval may be extended to every 42 or 56 days based on symptom stability. Initiation often involves a loading dose or more frequent administration (e.g., every 14 days) for the first few months.
References
Caron, P., et al. Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly. Journal of Clinical Endocrinology and Metabolism, 2002. 87(1), 99-104.
Caplin, M.E., et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. New England Journal of Medicine, 2014. 371(3), 224-233.
Gittoes, N.J., et al. Radiotherapy and lanreotide in the management of thyroid eye disease. European Journal of Endocrinology, 2005. 153(1), 23-28.
Bevan, J.S., et al. Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release lanreotide on growth hormone, insulin-like growth factor-I, and tumor size. Journal of Clinical Endocrinology and Metabolism, 2002. 87(10), 4554-4563.
Ruszniewski, P., et al. Lanreotide reduces the volume of polycystic liver in patients with autosomal dominant polycystic kidney disease. Gastroenterology, 2003. 125(2), 479-486.
Anthony, L., et al. Long-acting somatostatin analog therapy of malignant carcinoid syndrome. Digestive Diseases and Sciences, 1993. 38(7), 1297-1305.
Somatuline Depot (lanreotide) Injection Prescribing Information. Ipsen Biopharmaceuticals, Inc. Revised 2022.