A Single-Dose Comparison of the Acute Effects between the New Somatostatin Analog SOM230 and Octreotide in Acromegalic Patients

Abstract

Treatment with the somatostatin receptor (sst) subtype 2 predominant analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new somatostatin analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 microg octreotide and 100 and 250 microg SOM230 were given s.c. to 12 patients with active acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7 vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering effect of 250 microg SOM230 was significantly superior to that of octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one patient, the GH-lowering effect of octreotide was better than that of SOM230. Tolerability for SOM230 was good. Glucose levels were initially slightly elevated after octreotide and SOM230, compared with control day, whereas insulin levels were only significantly suppressed by octreotide. We conclude that SOM230 is an effective GH-lowering drug in acromegalic patients with the potential to increase the number of patients controlled during long-term medical treatment.

Function and expression of somatostatin receptors of the endocrine pancreas

“…Standard medical treatment includes octreotide, which acts predominantly via SSTR2 and more recently a panagonist, the peptidomimetic SOM230 which has a 30-40-fold higher binding affinity to SSTR1 and SSTR5 and a more potent long lasting effect on suppression of GH and IGF-I, as compared to octreotide Weckbecker et al, 2002). In humans, both octreotide and SOM230 (transiently) elevated blood glucose levels, however in contrast to octreotide, SOM230 did not inhibit insulin secretion (van der Hoek J. et al, 2004). The inhibition of insulin secretion in humans by octreotide and the lack thereof in SOM230-treated patients further supports the bulk of in vitro studies indicating insulin secretion is regulated via SSTR2.…”

High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial

“…Areas of potential interest are general safety, glucose metabolism and potential effects relating to the hepatobiliary tract (15,26). In our study, no patients withdrew from the study due to clinically or biochemically relevant adverse effects.…”

“…These findings may be explained based on the hypothesis that octreotide at higher doses could exert its activity via receptor subtypes other than SSTR2 for which the molecule has a lower affinity, such as SSTR5 (13). Indeed, in vitro and in vivo studies have suggested the importance of SSTR5 in mediating GH inhibition (14,15). Alternatively, elevated octreotide concentration may lead to SSTR2 upregulation or interfere with receptor metabolism (16).…”

“…Octreotide is the most widely used medical treatment for acromegaly; it is effective in more than 50% of patients, is well tolerated and has high compliance rates based on monthly i.m. injections (1,7,8,15). However, in patients not achieving optimal IGF1 control on conventional SSA therapy, current guidelines recommend other treatment modalities (pegvisomant and/or radiosurgery in the case of post-surgical treatment or surgery for those receiving primary medical treatment) (1).…”

Preclinical and clinical experiences with the role of somatostatin receptors in the treatment of pituitary adenomas

“…SOM230 suppressed GH secretion in primary cultures from human fetal pituitary cells (26). The preclinical reports of enhanced GH suppression via the combined activation of sst 2 and sst 5 receptors in cultures of GH-secreting pituitary adenomas initiated a proofof-concept clinical trial with SOM230 in 12 patients with active acromegaly (27). A single s.c. injection of 250 mg SOM230 compared with 100 mg OCT showed comparable efficacy in suppressing circulating GH concentrations in eight patients, and showed a significantly enhanced suppression in 3 of 12 acromegalic patients (27; Fig.…”