Horm Metab Res 2005; 37(10): 627-632
DOI: 10.1055/s-2005-870529
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Day-long Subcutaneous Infusion of Exenatide Lowers Glycemia in Patients with Type 2 Diabetes

K.  Taylor1 , D.  Kim1 , L.  L.  Nielsen1 , M.  Aisporna1 , A.  D.  Baron1 , M.  S.  Fineman1
  • 1Amylin Pharmaceuticals, Inc., San Diego, CA, USA
Further Information

Publication History

Received 19 July 2004

Accepted second revision 11 April 2005

Publication Date:
08 November 2005 (online)

Abstract

Exenatide (exendin-4) is an incretin mimetic with potential antidiabetic activity. This study examined the effects of a continuous subcutaneous (SC) infusion of exenatide (0.2, 0.4, 0.6, or 0.8 μg/kg/day) or placebo (PBO) on glycemic control over 23 h intervals. Twelve subjects with type 2 diabetes treated with metformin and/or diet received 10 infusions (4 exenatide, 6 PBO) on consecutive days. Exenatide was given in a dose-increasing design with at least one placebo infusion between each exenatide infusion, and with meals and a snack provided during the first 14 h of infusion. Plasma exenatide concentrations were dose-proportional. Plasma glucose (4 - 23 h) was lower in all exenatide arms compared to placebo (p < 0.0001). The change in insulin/glucagon ratio and amylin concentrations from pre-infusion to post-infusion was increased (p < 0.005, p < 0.05, respectively) in the combined exenatide arms, but remained unchanged in the placebo groups. Nausea and vomiting were the most common treatment emergent adverse events. Exenatide infusion also appeared to have positive effects on β-cell and α-cell function as measured by proinsulin/insulin ratios and mean glucagon concentrations. In summary, exenatide lowered plasma glucose during both prandial and fasting states when delivered as a continuous SC infusion over twenty-three hours, suggesting that exenatide can provide day-long glycemic control in patients with type 2 diabetes.

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Mark S. Fineman

Amylin Pharmaceuticals, Inc.

9360 Towne Centre Drive, Suite 110 · San Diego, CA 92121

Phone: +1 858 642-7212

Fax: +1 858 334-1212

Email: mfineman@amylin.com