Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients
with type 2 diabetes treated with metformin and a sulfonylurea.
Author(s): Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD.
Affiliation(s): International Diabetes Center and University of Minnesota, Minmneapolis, MN, USA.
Publication date & source: 2005, Diabetes Care. , 28(5):1083-91
OBJECTIVE: This study evaluated the effects of exenatide, a novel incretin
mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve
glycemic control with metformin-sulfonylurea combination therapy.
RESEARCH DESIGN AND METHODS: A 30-week, double-blind, placebo-controlled study
was performed in 733 subjects (aged 55 +/- 10 years, BMI 33.6 +/- 5.7 kg/m(2),
A1C 8.5 +/- 1.0%; means +/- SD) randomized to 5 microg subcutaneous exenatide
b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5
microg b.i.d. and arm B escalated to 10 microg b.i.d. Subjects continued taking
their dose of metformin and were randomized to either maximally effective (MAX)
or minimum recommended (MIN) doses of sulfonylurea.
RESULTS: Week 30 A1C changes from baseline (+/-SE) were -0.8 +/- 0.1% (10
microg), -0.6 +/- 0.1% (5 microg), and +0.2 +/- 0.1% (placebo; adjusted P <
0.0001 vs. placebo), yielding placebo-adjusted reductions of -1.0% (10 microg)
and -0.8% (5 microg). In the evaluable population, exenatide-treated subjects
were more likely to achieve A1C < or =7% than placebo-treated subjects (34% [10
microg], 27% [5 microg], and 9% [placebo]; P < 0.0001). Both exenatide arms
demonstrated significant weight loss (-1.6 +/- 0.2 kg from baseline each
exenatide arm, -0.9 +/- 0.2 kg placebo; P < or = 0.01 vs. placebo). Mild or
moderate nausea was the most frequent adverse event. The incidence of
mild/moderate hypoglycemia was 28% (10 microg), 19% (5 microg), and 13% (placebo)
and appeared lower with MIN than with MAX sulfonylurea treatment.
CONCLUSIONS: Exenatide significantly reduced A1C in patients with type 2 diabetes
unable to achieve adequate glycemic control with maximally effective doses of
combined metformin-sulfonylurea therapy. This improvement in glycemic control was
associated with no weight gain and was generally well tolerated.
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