Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function.