Octreotide: A long-acting inhibitor of endogenous hormone secretion for human metabolic investigations

Abstract

Octreotide is a recently available, FDA-approved, long-acting analog of somatostatin. The efficacy and tolerability of octreotide were evaluated in a series of protocols in healthy volunteers to assess its suitability for use in clinical investigations involving short-term inhibition of endogenous hormone secretion. Prolonged (270 minutes) hyperglycemic clamps were used to assess octreotide-mediated suppression of glucose-stimulated endogenous insulin secretion. Compared with a saline-control infusion, octreotide (30 ng/kg/min) suppressed stimulated insulin ( P < .0001) and C-peptide ( P < .0001) concentrations to basal levels. During insulin-induced hypoglycemia (plasma glucose < 40 mg/dL), octreotide (30 ng/kg/min) effectively suppressed the secretion of glucagon ( P < .05) and growth hormone ( P < .0005). In islet cell clamp studies, octreotide (30 ng/kg/min) suppressed C-peptide ( P < .001), glucagon ( P < .01), and growth hormone concentrations to below basal (fasting) levels in all subjects. Subsequent infusion of exogenous insulin, glucagon, and growth hormone resulted in predictable and stable concentrations of each hormone during octreotide-mediated suppression of their endogenous secretion. Consistent with the long half-life of octreotide (∼90 minutes), the concentrations of all three hormones remained suppressed below basal levels throughout a 60-minute observation period following the termination of octreotide infusion. In separate high-dose octreotide infusion studies, octreotide (60 ng/kg/min) did not produce any apparent additional metabolic effects, but was associated with an unacceptable degree of gastrointestinal side effects. These investigations demonstrate that octreotide, administered as a continuous intravenous infusion at a rate of 30 ng/kg/min, is a potent and well-tolerated inhibitor of basal and stimulated secretion of endogenous insulin, glucagon, and growth hormone. The efficacy, availability, practical convenience, and cost advantage of octreotide indicate a significant role for this somatostatin analog in studies of human metabolism.