THE EFFECT OF SINGLE DOSES OF PRAMLINTIDE ON GASTRIC-EMPTYING OF 2 MEALS IN MEN WITH IDDM

In a previous study we have shown that an intravenous infusion of pram lintide (an analogue of human amylin) delayed gastric emptying, but th e dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injectio ns of pramlintide on gastric emptying and to determine whether adminis tration of the drug before one meal has an impact on the subsequent me al. Eleven men with insulin-dependent diabetes mellitus were studied i n a double-blind, randomised, four-way crossover design. None had auto nomic neuropathy. Euglycaemia was maintained overnight before the stud y day. At -30 min the patients self-injected their usual morning insul in and at -15 min they injected the study drug (either placebo or 30, 60 or 90 mu g pramlintide) subcutaneously. At 0 min they ate a standar d meal consisting of a pancake, labelled with Tc-99m, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal , but on this occasion the pancake was labelled with In-111. All three doses of pramlintide delayed emptying of the solid component of the f irst meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolong ation in the time to peak plasma 3-OMG level (p < 0.0001) after the fi rst meal but there was no difference after the second meal.