Pasireotide in Acromegaly: A Review

Abstract

Pasireotide (Signifor(®), Signifor(®) LAR) is a somatostatin analogue recently approved for the treatment of acromegaly. Unlike the first-generation agents, octreotide and lanreotide, which bind preferentially to somatostatin receptor (SSTR)-2, pasireotide binds to multiple SSTRs. This article reviews the clinical use and summarizes the pharmacological properties of intramuscular pasireotide in the treatment of acromegaly. The efficacy of pasireotide 40 mg every 28 days was superior to that of intramuscular octreotide 20 mg every 28 days with regard to biochemical control in a 12-month, phase III trial in medically naive patients. Similarly, in a 6-month, phase III trial in patients with acromegaly inadequately controlled with somatostatin analogues for at least 6 months, the efficacy of pasireotide 40 or 60 mg was superior to that of continued octreotide 30 mg or lanreotide autogel 120 mg (each drug was administered once every 28 days) with regard to biochemical control. The tolerability profile of intramuscular pasireotide is generally similar to that of first-generation agents, except for a higher incidence of hyperglycaemia-related adverse events with pasireotide. In clinical trials, the risk of developing pasireotide-associated hyperglycaemia was numerically greater in patients categorized as diabetic or prediabetic at baseline than in those with normal glucose tolerance. Careful monitoring of glycaemic status is required prior to and during pasireotide treatment and antidiabetic therapy should be commenced as indicated. Thus, in the treatment of acromegaly, pasireotide may be a more effective somatostatin analogue than other approved agents of the same class; however, the increased risk of hyperglycaemia needs to be considered and proactively managed.

Insulinooporność w chorobach endokrynnych — sposoby terapii

“…Although the results of treatment in control of acromegaly look promising, the observed adverse effect on carbohydrate metabolism is an important limiting factor. It stems from a reduction in insulin secretion and weakening of the incretin effect [16]. Incretins seem to be most effective in the control of hyperglycaemia during pasireotide therapy [17].…”

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

“…Paracrine signaling occurs through binding of SST to receptors on alpha‐ and beta‐cells, and 5 different SST receptor subtypes have been cloned . Somatostatin analogs such as octreotide were developed for the treatment of acromegaly and adult Cushing's disease in humans . There are only 2 published studies of octreotide use in horses to date which examined its effects on gastric pH in ponies and testicular function in pony stallions .…”

“…3,4 Somatostatin analogs such as octreotide were developed for the treatment of acromegaly and adult Cushing's disease in humans. 5,6 There are only 2 published studies of octreotide use in horses to date which examined its effects on gastric pH in ponies and testicular function in pony stallions. 7,8 Somatostatin solution administered intravenously as a continuous rate infusion suppresses insulin secretion in horses.…”

Glucose and insulin response after intravenous and subcutaneous somatostatin administration in healthy horses

“…The bioactivity of somatostatin is short‐lived, so synthetic analogs with longer plasma half‐lives have been developed, including long‐acting octreotide and lanreotide. Somatostatin analogs have been used in humans for the treatment of Cushing disease and acromegaly (Hofland, ; McKeage, ), as well as for the management of hyperinsulinemic forms of obesity (Bertoli et al, ; Boehm, ; Gambineri et al, ; Hansen et al, ; Tzotzas et al, ). Studies in horses have reported effects on gastric pH and testicular function in ponies (Aurich et al, ; Sojka et al, ), with the most recent study evaluating the effects on insulin responses (Frank et al, ).…”