Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.
OBJECTIVE
This study evaluates the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses.


METHODS
A triple-blind, placebo-controlled, 30-week study at 82 U.S. sites was performed with 336 randomized patients. In all, 272 patients completed the study. The intent-to-treat population baseline was 53 +/- 10 years with BMI of 34.2 +/- 5.9 kg/m(2) and HbA(1c) of 8.2 +/- 1.1%. After 4 weeks of placebo, subjects self-administered 5 microg exenatide or placebo subcutaneously twice daily for 4 weeks followed by 5 or 10 microg exenatide, or placebo subcutaneously twice daily for 26 weeks. All subjects continued metformin therapy.


RESULTS
At week 30, HbA(1c) changes from baseline +/- SE for each group were -0.78 +/- 0.10% (10 microg), -0.40 +/- 0.11% (5 microg), and +0.08 +/- 0.10% (placebo; intent to treat; adjusted P < 0.002). Of evaluable subjects, 46% (10 microg), 32% (5 microg), and 13% (placebo) achieved HbA(1c) < or =7% (P < 0.01 vs. placebo). Exenatide-treated subjects displayed progressive dose-dependent weight loss (-2.8 +/- 0.5 kg [10 microg], -1.6 +/- 0.4 kg [5 microg]; P < 0.001 vs. placebo). The most frequent adverse events were gastrointestinal in nature and generally mild to moderate. Incidence of mild to moderate hypoglycemia was low and similar across treatment arms, with no severe hypoglycemia.


CONCLUSIONS
Exenatide was generally well tolerated and reduced HbA(1c) with no weight gain and no increased incidence of hypoglycemia in patients with type 2 diabetes failing to achieve glycemic control with metformin.
DeFronzo
Ralph A
RA
Division of Diabetes, University of Texas Health Science Center, San Antonio, TX, USA.
Ratner
Robert E
RE
Han
Jenny
J
Kim
Dennis D
DD
Fineman
Mark S
MS
Baron
Alain D
AD
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011384:Proinsulin / Q000097:blood; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects
D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010455:Peptides; D011384:Proinsulin; D014688:Venoms