Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes.
OBJECTIVE
In patients with type 2 diabetes, exenatide reduces A1C, postprandial and fasting glucose, and weight. In this study we investigated the effects of continuous exenatide administration from a long-acting release (LAR) formulation.


METHODS
In this randomized, placebo-controlled phase 2 study, exenatide LAR (0.8 or 2.0 mg) was administered subcutaneously once weekly for 15 weeks to subjects with type 2 diabetes (n = 45) suboptimally controlled with metformin (60%) and/or diet and exercise (40%): 40% female, A1C (mean +/- SD) 8.5 +/- 1.2%, fasting plasma glucose 9.9 +/- 2.3 mmol/l, weight 106 +/- 20 kg, and diabetes duration 5 +/- 4 years.


RESULTS
From baseline to week 15, exenatide LAR reduced mean +/- SE A1C by -1.4 +/- 0.3% (0.8 mg) and -1.7 +/- 0.3% (2.0 mg), compared with +0.4 +/- 0.3% with placebo LAR (P < 0.0001 for both). A1C of < or =7% was achieved by 36 and 86% of subjects receiving 0.8 and 2.0 mg exenatide LAR, respectively, compared with 0% of subjects receiving placebo LAR. Fasting plasma glucose was reduced by -2.4 +/- 0.9 mmol/l (0.8 mg) and -2.2 +/- 0.5 mmol/l (2.0 mg) compared with +1.0 +/- 0.7 mmol/l with placebo LAR (P < 0.001 for both). Exenatide LAR reduced self-monitored postprandial hyperglycemia. Subjects receiving 2.0 mg exenatide LAR had body weight reductions (-3.8 +/- 1.4 kg) (P < 0.05), whereas body weight was unchanged with both placebo LAR and the 0.8-mg dose. Mild nausea was the most frequent adverse event. No subjects treated with exenatide LAR withdrew from the study.


CONCLUSIONS
Exenatide LAR offers the potential of 24-h glycemic control and weight reduction with a novel once-weekly treatment for type 2 diabetes.
Kim
Dennis
D
Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA. dkim@amylin.com
MacConell
Leigh
L
Zhuang
Dongliang
D
Kothare
Prajakti A
PA
Trautmann
Michael
M
Fineman
Mark
M
Taylor
Kristin
K
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D001835:Body Weight / Q000187:drug effects; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*; D015431:Weight Loss
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide