Signifor, Signifor LAR
Evidence Grade A — Regulatory approved. 746 published studies. 71 registered clinical trials.
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Pasireotide (sold as Signifor) is the first and only medication approved specifically for Cushing's disease — a serious condition caused by a pituitary tumour that floods the body with the stress hormone cortisol, leading to weight gain, high blood sugar, bone thinning, and muscle weakness. It is also approved for acromegaly when other somatostatin treatments have not worked well enough.
746 published studies: 559 human, 41 animal, 67 in-vitro, 238 reviews
Pasireotide is marketed as Signifor for Cushing's disease (approved December 2012) and Signifor LAR for acromegaly (approved December 2014). In Cushing's disease, approximately 26% of patients achieved normal cortisol levels after six months of treatment. In acromegaly, pasireotide LAR achieved hormone control in 31.3% of patients versus 19.2% for octreotide LAR.
The main limitation of pasireotide is a significant impact on blood sugar — diabetes occurred in 19–26% of patients in clinical trials, substantially higher than with octreotide or lanreotide. This is because the broader receptor profile also suppresses insulin release more strongly. As a result, pasireotide is typically reserved for patients who have not responded adequately to other somatostatin analogues, rather than used as a first-line treatment.
While octreotide and lanreotide mainly target two of the five somatostatin receptors, pasireotide binds to four of them. This broader coverage is critical for treating Cushing's disease because the pituitary tumours that cause this condition predominantly express the receptor type (SST5) that older somatostatin analogues barely reach. By targeting SST5 with high affinity, pasireotide can directly suppress the excess cortisol-stimulating hormone (ACTH) that these tumours produce.
In Cushing's disease, approximately 26% of patients achieved normal cortisol levels after six months of treatment — a modest response rate, but meaningful given the severity of the condition and the limited alternatives available when surgery does not cure it. For acromegaly, pasireotide showed superiority over octreotide in hormone control (31% versus 19%). The significant drawback is its impact on blood sugar. Pasireotide suppresses insulin release more aggressively than older somatostatin drugs, and new-onset diabetes occurred in 19-26% of patients in clinical trials. This makes blood sugar management a co-treatment concern and limits pasireotide to second-line use in most cases. Oral cortisol synthesis inhibitors (like osilodrostat) have emerged as alternative non-surgical approaches for Cushing's disease.
An Open-label, Multi-center, Expanded Treatment Protocol of Pasireotide LAR in Patients With Acromegaly
Compassionate Use of SOM230 for Hyperinsulinemic/Hypoglycemia
Study in Healthy Subjects to Investigate the Relative Bioavailability and Safety of Pasireotide After Single Subcutaneous Dose Administration Using a Reusable ServoPen With Cartridge as Compared to Administration Using a Syringe Drawn From an Ampule
Effects of Pasireotide Lar Therapy on Bone Metabolism
Pasireotide as Maintenance Treatment in Synovial Sarcoma and Desmoplastic Small Round Cell Tumor
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Exenatide was the first GLP-1 receptor agonist approved anywhere, reaching the market as Byetta in April 2005. The once-weekly formulation Bydureon followed in 2012. Clinical trials showed blood sugar reductions (HbA1c) of 1.6–1.9% and modest weight loss of 2–4 kg. The EXSCEL cardiovascular outcomes trial, involving over 14,700 patients, showed a trend toward cardiovascular benefit but narrowly missed statistical significance. While exenatide was groundbreaking as the first in its class, it has been largely overtaken by newer GLP-1 treatments that offer greater efficacy, less frequent dosing, and proven cardiovascular benefits. It remains available and in clinical use, particularly in combination products.
Lixisenatide was marketed as Adlyxin in the US (approved July 2016), though it has since been discontinued in the US market. The ELIXA cardiovascular trial, involving over 6,000 patients, was the first cardiovascular outcomes trial for any GLP-1 medication to report results. It showed a neutral cardiovascular profile — neither harmful nor beneficial — meeting safety requirements but not demonstrating the heart benefits later shown by semaglutide and liraglutide. Lixisenatide found its primary clinical role in combination with basal insulin, marketed as Soliqua (lixisenatide plus insulin glargine). This combination addresses both fasting blood sugar (via insulin) and post-meal spikes (via lixisenatide) in a single daily injection. As a standalone treatment, it has been largely superseded by more potent GLP-1 medications.
Pramlintide is marketed as Symlin (approved March 2005) and remains the only approved amylin-based treatment. It is used alongside mealtime insulin in both type 1 and type 2 diabetes. Clinical trials showed modest blood sugar improvements (HbA1c reductions of 0.2–0.6%) and approximately 2.3 kg of weight loss — less dramatic than GLP-1 treatments but meaningful as an add-on therapy. Symlin carries a boxed warning for severe hypoglycaemia, particularly when combined with insulin, and requires careful dose adjustment. Practical uptake has been limited by the need for separate injections at each meal alongside existing insulin injections. Despite its modest clinical impact, pramlintide remains the only medication that addresses the amylin deficiency in diabetes, filling a distinct biological role that GLP-1 treatments do not cover.
