The incretin mimetic exenatide as a monotherapy in patients with type 2 diabetes.
BACKGROUND
Exenatide is an adjunctive therapy for type 2 diabetes, and preliminary evidence suggests that its glucoregulatory effects may be similar in the absence of oral therapy.


METHODS
Study A was a randomized, double-blind, placebo-controlled study of 99 patients with type 2 diabetes that received either 10 microg twice-daily, 10 microg once-daily, or 20 microg once-daily exenatide or placebo for 28 days in the absence of background pharmacotherapy. Study B was an open-label extension of a short-term study of 127 patients with type 2 diabetes treated with metformin or diet and exercise. Patients received exenatide 5 microg twice-daily for 4 weeks followed by 10 microg for 26 weeks. Subjects treated with metformin continued oral therapy.


RESULTS
Monotherapeutic treatment with 10 microg of exenatide twice-daily for 28 days resulted in significant mean reductions in glycosylated hemoglobin (A1C) of -0.4 +/- 0.1% and fasting plasma glucose of -36.1 +/- 11.0 mg/dL compared to increases of +0.2 +/- 0.1% and +11.0 +/- 12.7 mg/dL with placebo. Self-monitored blood glucose profiles showed significant mean reductions in daily blood glucose concentrations in exenatide-treated patients compared to placebo. Exenatide treatment for 30 weeks in an open-label extension study resulted in similar mean reductions from baseline in A1C and body weight in patients treated with diet and exercise alone (-1.0 +/- 0.2% and -4.3 +/- 1.3 kg, respectively) as those treated on a background of metformin (-0.9 +/- 0.1% and -3.7 +/- 0.5 kg, respectively). In both studies, the most frequent adverse events were gastrointestinal and predominantly mild to moderate in intensity. Incidence of mild-to-moderate hypoglycemia was low, with no severe hypoglycemia.


CONCLUSIONS
Exenatide twice-daily monotherapy resulted in glycemic improvements and reductions in body weight comparable to that of exenatide combination therapy with metformin in patients with type 2 diabetes.
Nelson
Patric
P
Amylin Pharmaceuticals Inc., San Diego, California, USA.
Poon
Terri
T
Guan
Xuesong
X
Schnabel
Catherine
C
Wintle
Matthew
M
Fineman
Mark
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003927:Diet, Diabetic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010865:Pilot Projects; D010919:Placebos; D014688:Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D010919:Placebos; D014688:Venoms