No abstract

The effect on gut motility of a single subcutaneous injection of 50 μg of the long-acting somatostatin analogue, SMS 201–995, was investigated in 8 normal volunteers who took a drink containing ^99mTc and lactulose with a mixed meal. The rate of gastric emptying was assessed by disappearance of the isotope from the stomach area as measured by a gamma camera, and mouth-to-caecum transit time (MCTT) was measured by the appearance of hydrogen in the breath. Gastric emptying was accelerated, with a significant reduction of the time taken to 50% isotope disappearance (37.2 ± 3.3 min during control study vs 23.3 ± 3.4 min after SMS injection; p < 0.01). In contrast, MCTT was prolonged from 57.3 ± 9.4 min (control) to 203.6 ± 14.7 min after SMS (p < 0.001).

The effects of guar granules sprinkled over food on carbohydrate and lipid metabolism were studied in a double-blind cross-over trial in 18 patients with non-insulin-dependent diabetes mellitus (mean +/- SEM age 61.3 +/- 2.5 years). Five-gram guar granules (Guarem, Rybar Laboratories, Amersham, Bucks) were sprinkled over food at each main meal for 4 weeks, and during a 4-week placebo period (separated by a 2-week 'wash-out' period), 5 g wheat bran was taken in the same way. Diabetic treatment was not changed during the study. Mean fasting plasma glucose (FPG) concentration and glycosylated haemoglobin (HbA1) concentration after treatment were significantly lower than after the placebo period (FPG 8.29 +/- 0.47 vs 8.78 +/- 0.53 mmol/l, p less than 0.05; HbA1: 8.70 +/- 0.39 vs 9.09 +/- 0.39%, p less than 0.05). There was a 50% reduction in the incremental area under the postprandial glycaemic curve when guar was eaten with a standardized test meal. Total plasma cholesterol decreased from 5.79 +/- 0.29 to 5.19 +/- 0.22 mmol/l (p less than 0.05) after the guar treatment period. Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.

Oral administration of SMS 201-995 (SMS), a subcutaneously injectable somatostatin analogue, was investigated in five healthy volunteers, who drank 2 mg of SMS with 75 g of glucose. Mean maximal plasma SMS concentrations after the 2 mg oral dose were comparable with those after subcutaneous injection of 50 micrograms, although the peak was delayed (90 vs 15 min). Biological activity of absorbed SMS was shown by significant and lasting suppression of plasma insulin concentrations, resulting in significant hyperglycaemia at 90 and 120 min compared with the control study. The feasibility of oral administration of SMS may extend its use in the treatment of acromegaly and gut endocrine tumours. Other peptide hormone analogues, structurally 'protected' against enzymatic degradation, may also be active orally and thus be useful therapeutically.