Effects of SMS 201-995 on intermediary metabolism and endocrine status in normal and diabetic humans

The hormonal and metabolic effects of the somatostatin analogue SMS 201-995 have been examined in normal and diabetic humans. When 50 micrograms of analogue was administered subcutaneously at 8 A.M. and 5:30 P.M., growth hormone secretion over 24 hours was not significantly affected, and the nocturnal growth hormone surge persisted in normal subjects and in type II diabetic patients. Insulin secretion was suppressed in both groups, but glucose tolerance deteriorated only in the normal subjects. Gastrointestinal side effects developed in both groups. Subcutaneous administration of 50 micrograms of SMS 201-995 at 11 P.M. decreased nocturnal growth hormone secretion (peak, 5 +/- 2 milliunits/liter versus 23 +/- 6 milliunits/liter; p less than 0.01) in normal subjects. Postprandial circulating glucose and insulin levels the following day were unaffected by SMS 201-995, and no side effects were observed. In type I diabetic patients receiving a variable rate insulin infusion overnight to maintain normoglycemia, SMS 201-995 (50 micrograms) administered at 11 P.M. decreased insulin requirements for two to three hours after injection. Insulin sensitivity thereafter was unaffected despite suppression of growth hormone secretion. Alternative dosage regimens are necessary to suppress growth hormone release over 24 hours and to minimize side effects in type II diabetes. Administration of the analogue in the late evening suppresses growth hormone secretion overnight, but the "dawn phenomenon" persists in type I diabetic patients.