Endocrine Abstracts

Somatostatin analogues (SSAs) approved to treat acromegaly tend to suppress postprandial insulin/glucagon secretion and can worsen glucose tolerance. COR-005, a novel SSA, is under investigation for treatment of acromegaly. In rodents, COR-005 effectively inhibits GH secretion with 10,000-fold greater potency compared with insulin release suppression. We sought to determine for the first time the effects of COR-005 on postprandial glucose in humans.

The pharmacodynamic effects of single subcutaneous doses of COR-005 300, 900, and 1800 μg, octreotide 300 μg and placebo on glucose, insulin and glucagon dynamics were investigated for 4 h after intake of a mixed meal in eight healthy male subjects using a randomized cross-over design.

Following COR-005 300 and 900 μg, there were slight increases in maximum blood glucose concentrations (9.76±1.00 and 9.73±1.31 vs 7.56±0.93 mmol/l) and in the 4-h blood glucose AUEC_Glucose compared to placebo (26.13±2.18, 28.86±3.82 vs 23.02±1.83 mmolxh/l). A higher increase was observed after injection of COR-005 1800 μg and the highest after octreotide 300 μg (AUEC_Glucose: 33.56±4.71 and 38.69±5.79 mmolxh/l). Octreotide significantly suppressed plasma insulin and glucagon secretion compared to placebo (AUEC_Insulin 15.56±2.02 vs 44.29±10.65 μUxh/ml and AUEC_Glucagon 135.5±55.1 vs 363.2±40.9 pgxh/ml) whereas COR-005 caused only a dose-dependent delay in insulin and glucagon secretion but had no significant effect on AUEC_Insulin or AUEC_Glucagon.

After intake of a mixed meal, COR-005 single doses up to 900 μg had no significant effect on total insulin and glucagon secretion compared to placebo and a marginal effect on blood glucose. COR-005 1800 μg less strongly inhibited postprandial insulin and glucagon compared to octreotide. COR-005 might offer a reduced risk of hyperglycemia relative to other SSAs currently used to treat acromegaly.