Abstract
Background
Studies of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) are needed to
determine the durability of metabolic response and tolerability associated with long-term
treatment.
Objective
The present study was conducted to provide long-term data on glycemic control, weight
changes, and tolerability of exenatide 10 μg BID treatment in patients with type 2
diabetes mellitus who have failed to achieve glycemic targets with oral antihyperglycemic
medication.
Methods
In this uncontrolled, open-label trial with treatment up to 156 weeks, patients received
exenatide 10 μg BID while continuing treatment with metformin and/or a sulfonylurea
(SFU). Intent-to-treat (ITT), 52-, 100-, and 132-week completer populations were defined.
Metabolic changes were analyzed in the completer and ITT populations; adverse events
(AEs) were summarized in the ITT population. Descriptive statistics were used for
absolute and change-from-baseline data. Within-treatment comparisons were conducted
using the paired t test.
Results
Of 155 patients in the ITT population (mean [SD]: age, 59 [9] years; 56% female; duration
of diabetes, 9.1 [5.9] years; weight, 88.8 [16.5] kg; body mass index, 31.9 [4.7]
kg/m2; hemoglobin [Hb] A1c, 8.7% [1.2%]), 133, 111, and 103 patients completed 52, 100, and 132 weeks of treatment,
respectively. In the ITT population, the mean (SE) change in HbA1c from baseline to week 132 was −1.0% (0.10%) (P < 0.0001). In patients completing 52, 100, and 132 weeks, HbA1c changes from baseline to end point were −1.3% (0.10%), −1.0% (0.12%), and −1.0 (0.13%)
(P < 0.0001), with 40% of patients achieving HbA1c <7% at 132 weeks. Patients in the ITT and completer populations experienced mean
(SE) weight changes of −3.7 (0.39) kg and −3.9 (0.51) kg (P < 0.0001) at week 132. Improved glycemic control and weight loss occurred in 63%
of patients in the completer population at week 132. In addition, 38% of completers
at week 132 achieved HbA1c <7% without weight gain. No relationship was found between the development of antiexenatide
antibodies and change in HbA1c. The most common AEs were gastrointestinal in nature, reported in 46% of patients
and leading to discontinuation in 7 cases. Serious AEs were reported in 26% of patients,
and 18% withdrew due to a treatment-emergent AE. Of 24% of patients in whom hypoglycemia
was reported, 22% were on SFU or metformin + SFU combination, and 2% were on metformin.
Conclusions
The findings from this open-label, single-arm study characterized the response to
exenatide 10 μg BID for up to 132 weeks. Significant, persistent improvements in HbA1c and weight were observed in patients receiving exenatide BID, with reported AEs consistent
with those from studies of shorter duration. ClinicalTrials.gov identifier: NCT00044668.
Key words
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Article info
Publication history
Published online: May 18, 2012
Accepted:
April 20,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
