The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus

To explore further the effects of the human amylin analog pramlintide on ov erall glycemic control and postprandial responses of circulating glucose, g lucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male t ype 1 diabetic patients were examined in a double-blind, placebo-controlled , crossover study. Pramlintide (30 mu g four times daily) or placebo were a dministered for 4 weeks, after which a daytime blood profile (8:30 AM to 4: 30 PM) was performed. Serum fructosamine was decreased after pramlintide (3 14 +/- 14 mu mol/L) compared with placebo (350 +/- 14 mu mol/L, P =.008). O n the profile day, the mean plasma glucose (8.3 +/- 0.7 v 10.2 +/- 0.8 mmol /L, P =.04) and postprandial concentrations (incremental areas under the cu rve [AUCs] from 0 to 120 minutes) were significantly decreased during praml intide administration (P <.01 for both) despite comparable circulating insu lin levels (359 +/- 41 v 340 +/- 35 pmol/L). Mean blood glycerol values wer e reduced (0.029 +/- 0.004 v 0.040 +/- 0.004 mmol/L, P =.01) and blood alan ine levels were elevated (0.274 +/- 0.012 v 0.246 +/- 0.008 mmol/L, P =.03) after pramlintide versus placebo. Blood lactate concentrations did not dif fer during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished (P =.02) , and a similar trend was observed following lunch. In addition, peak plasm a glucagon concentrations 60 minutes after breakfast (45.8 +/- 7.3 v 72.4 /- 8.0 ng/L, P =.005) and lunch (47.6 +/- 9.0 v 60.9 +/- 8.2 ng/L, P =.02) were both decreased following pramlintide. These data indicate that pramlin tide (30 mu g four times daily) is capable of improving metabolic control i n type 1 diabetics. This may relate, in part, to suppression of glucagon co ncentrations. Longer-term studies are required to ascertain whether these f indings are sustained over time. Copyright (C) 1999 by W.B. Saunders Compan y.