Metabolic Effects of Long-Acting Somatostatin Analogue (Sandostatin) in Type I Diabetic Patients on Conventional Therapy

Abstract

We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug regimens for 12 wk. Eight patients received a low dose (10 micrograms) of the analogue, 9 received a high dose (50 micrograms) of the analogue, and 9 received placebo subcutaneously before breakfast and dinner. Twenty-four-hour serum glucose, free insulin, plasma growth hormone (GH), and glucagon profiles were obtained before and during treatment at 4-wk intervals. The mean age, duration of diabetes, daily insulin dose, and body weight were not significantly different among the groups. The mean weekly capillary blood glucose values and exogenous insulin requirements were not changed by the SMS 201-995 therapy. Mean glycosylated hemoglobin A1 levels were unchanged in both the analogue- and placebo-treated groups at wk 12. Basal and postprandial glucose, free insulin, GH, and glucagon profiles were not influenced by the SMS 201-995 therapy throughout the study. Nocturnal glucose turnover rates (D-[3-3H]glucose technique) remained unaltered by the analogue therapy. Dose-dependent gastrointestinal (GI) adverse effects (e.g., diarrhea) were documented in the analogue-treated patients. Visual acuity and fundic photomicrographs of our patients were not changed by the analogue therapy. In conclusion, the prominent adverse GI effects our patients experienced preclude the use of larger doses of the analogue that may be necessary to suppress GH and glucagon and improve glucose control in type I diabetic patients.

Minireview: Glucagon in the Pathogenesis of Hypoglycemia and Hyperglycemia in Diabetes

“…Administration of a long-acting somatostatin analog to people with type 1 diabetes over days to weeks has been reported to reduce glycemia in some (99) but not other (100,101) studies. However, it increases sensitivity to insulin (102,103), perhaps because of suppression of glucagon secretion.…”

The effects of somatostatin analogues on glycaemia in the treatment of neuroendocrine tumours

“…Ipp et al 27 reported that exogenous somatostatin impairs the clearance of exogenous insulin and therefore would reduce insulin requirements. However, a study by Osei et al 28 assessing the metabolic effects of sandostatin LAR on T1DM found no significant change in FPG, HbA1c or exogenous insulin requirements after 3 months of treatment with SSA in T1DM patients.…”

“…Ipp et al 27 reported that exogenous somatostatin impairs the clearance of exogenous insulin and therefore would reduce insulin requirements. However, a study by Osei et al 28 assessing the metabolic effects of sandostatin LAR…”

Preventive effects of octreotide (SMS 201‐995) on diabetic ketogenesis during insulin withdrawal.

“…On the second occasion patients were treated with the somatostatin analogue octreotide which led to a marked suppression of ,-hydroxybutyrate, acetoacetate and (Grossmann et al, 1989;Osei et al, 1989;Spinas et al, 1985). Gerich et al (1975) previously published that continuous intravenous infusion of native somatostatin can prevent the development of ketoacidosis in type I diabetic patients, and specifically showed diminished or absent increments of P-hydroxybutyrate, FFA, glucose and glucagon levels.…”