Long-term effects of adding exenatide to a regimen of metformin and/or sulfonylurea in type 2 diabetes: an uncontrolled, open-label trial in Hungary.

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/m(2); hemoglobin [Hb] A(1c), 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 HbA(1c) from baseline to week 132 was -1.0% (0.10%) (P < 0.0001). In patients completing 52, 100, and 132 weeks, HbA(1c) 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 HbA(1c) <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 HbA(1c) <7% without weight gain. No relationship was found between the development of antiexenatide antibodies and change in HbA(1c). 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 HbA(1c) and weight were observed in patients receiving exenatide BID, with reported AEs consistent with those from studies of shorter duration. ClinicalTrials.gov identifier: NCT00044668.