Effects of the new somatostatin analogue (BIM 23014) on blood glucose homeostasis in normal men

Abstract

Changes in blood glucose homeostasis induced by the new somatostatin analogue BIM 23014 (BIM) were studied. Eight normal men (study 1) received either vehicle or 1000, 2000 and 3000 micrograms BIM as a 24 h s.c. infusion. Blood glucose, plasma insulin, C-peptide, glucagon and growth hormone (GH) were measured before treatment and then hourly for 24 h. In five normal men (study 2) an oral glucose tolerance test (OGTT) was performed during vehicle infusion and then on days 1 and 7 of a continuous s.c. infusion of 2000 micrograms BIM daily for 7 days. The same biological parameters as in study 1 were measured before OGTT and then twice-hourly for 5 h. Dose-dependent and transient glucose intolerance was observed in the first half of study 1. Except for glucagon, BIM significantly (P < 0.01) reduced plasma insulin, C-peptide and GH levels. In study 2 BIM infusion induced glucose intolerance and a drop in plasma insulin and C-peptide on day 1 which disappeared on day 7 of infusion. Higher on day 7 than on day 1, plasma GH secretion was significantly (P < 0.01) reduced throughout BIM infusion. In contrast plasma glucagon levels were not modified at any time. Side-effects were abdominal cramps and diarrhoea which were observed in most subjects when increasing BIM daily dose. In conclusion, BIM infusion induced transient changes in glucose homeostasis and insulin secretion in normal men. By contrast, plasma GH levels remained reduced throughout the treatment. BIM appears to be a useful tool to selectively inhibit GH secretion.

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide

“…1). In 3 patients mean GH in multiple sampling was below 5 pg/ I; however, in only 1 of them was GH reduced to less than 2^g /1 during OGTT. In 5 out of 7 patients who demonstrated a sustained reduction in GH during the therapy the TRH injection stimulated a paradoxical increase of GH before treatment.…”

“…In previous studies BIM 23014 proved to be a useful tool in selectively inhibiting GH secretion (1)(2)(3). The effects of the slow-release formulation of the product have been reported in a limited number of patients with treatment period not exceeding 12 months (4-6).…”

Octreotide suppresses the incretin glucagon-like peptide (7-36) amide in patients with acromegaly or clinically nonfunctioning pituitary tumors and in healthy subjects

“…The healthy subjects had a more homogeneous distribution of GLP-1 and insulin concentrations and their GLP-1 and insulin escape was already significant in the St-M after only 1 week of treatment. An early escape of insulin and lack of GH escape have also been found during treatment with the somatostatin analog BIM 23014 (18).…”

Therapeutic options in the management of acromegaly: focus on lanreotide Autogel&reg;

“…GH counteracts the effects of insulin by inhibiting the phosphorylation of the insulin receptor. Moreover, GH also inhibits the phosphorylation of one of the proximate molecules of the insulin signaling cascade, insulin receptor substrate-1 in response to insulin (Kuhn et al 1992). In acromegaly, several studies have shown that increased GH induces insulin resistance (Kasayama et al 2000).…”

“…The acute effects of subcutaneously infused lanreotide were studied in healthy subjects. Oral glucose tolerance worsened during the first day of administration, but was restored on day 7 while drug administration continued (Kuhn et al 1992). In a study in 27 patients the homeostasis model assessment (HOMA) index improved, but not the quantitative insulin check index (QUICKI) index (Ronchi et al 2003).…”