Pramlintide, an adjunct treatment to mealtime insulin for patients with type 2 and type 1 diabetes, aids glycemic control by suppressing postprandial glucagon secretion, slowing gastric emptying, and enhancing satiety. Because gastric emptying affects oral medication absorption, this placebo-controlled, single-blind, crossover study examined the absorption of 1000 mg of acetaminophen elixir administered -2, -1, 0, +1, and +2 hours relative to pramlintide (120 microg) or 0 hours relative to placebo in 24 patients with type 2 diabetes. When acetaminophen administration occurred 0, +1, or +2 hours relative to pramlintide, the maximum observed plasma concentration of acetaminophen decreased 14% to 29%, and time to maximum observed plasma concentration increased by 0.8 to 1.2 hours compared with administration 0 hours relative to placebo. Pramlintide treatment slowed but did not alter the extent of acetaminophen absorption (area under the concentration-time curve). No serious adverse events or withdrawals were reported. Oral agents should be administered at least 1 hour before or 2 hours after pramlintide injection if rapid onset of action is required for efficacy.