Exenatide improves glycemic control and reduces body weight in subjects with type 2 diabetes: a dose-ranging study.
BACKGROUND
Exenatide is the first of a new class of agents known as incretin mimetics that are in development for the treatment of type 2 diabetes. Exenatide has been shown to reduce fasting and postprandial glucose in patients with type 2 diabetes, as well as provide sustained reductions in hemoglobin A 1c (HbA 1c). This study was designed to assess the dose dependencies of the glucoregulatory effects and tolerability of exenatide when added to diet and exercise or metformin monotherapy in patients with type 2 diabetes.


METHODS
In this randomized, triple-blinded, placebo-controlled Phase 2 clinical trial, 156 patients were randomized to placebo or exenatide at 2.5, 5.0, 7.5, or 10.0 microg administered b.i.d. for 28 days.


RESULTS
After 28 days of therapy, exenatide was associated with significant (P < 0.0001, linear contrast testing), dose-dependent reductions in HbA 1c (0.1 +/- 0.1%, -0.3 +/- 0.1%, -0.4 +/- 0.1%, +/-0.5 +/- 0.0%, and -0.5 +/- 0.1% for placebo and 2.5, 5.0, 7.5, and 10.0 microg b.i.d. exenatide, respectively) and significant (P = 0.0006, linear contrast testing) reductions in fasting plasma glucose (+6.8 +/- 4.1, -20.1 +/- 5.2, -21.2 +/- 3.9, -17.7 +/- 4.8, and -17.3 +/- 4.4 mg/dL for placebo and 2.5, 5.0, 7.5, and 10.0 microg b.i.d. exenatide, respectively) by Day 28. These reductions were similar for patients treated with diet/exercise and those treated with metformin. In addition, patients receiving exenatide exhibited dose-dependent reductions in body weight (0.0 +/- 0.3, -0.7 +/- 0.3, -0.7 +/- 0.2, -1.4 +/- 0.3, and -1.8 +/- 0.3 kg for placebo and 2.5, 5.0, 7.5, and 10.0 microg b.i.d. exenatide, respectively; P < 0.01 for 7.5 and 10.0 microg b.i.d. exenatide doses compared with placebo) at Day 28. The most common adverse event was mild-to-moderate nausea that was dose-dependent (seven of 123 patients randomized to exenatide withdrew from the study because of gastrointestinal effects).


CONCLUSIONS
Exenatide dose-dependently improved glycemic control and reduced body weight over 28 days in patients with type 2 diabetes treated with diet/exercise or metformin.
Poon
Terri
T
Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA.
Nelson
Patric
P
Shen
Larry
L
Mihm
Michael
M
Taylor
Kristin
K
Fineman
Mark
M
Kim
Dennis
D
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D010919:Placebos; D044469:Racial Groups; D012107:Research Design; D014688:Venoms / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects*
D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D010455:Peptides; D010919:Placebos; D014688:Venoms