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

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• 作者：Tibor Ivá ; nyi ; MD¹ ; ^{ivanyi_tibor@lilly.com} ; Jó ; zsef Fö ; vé ; nyi ; MD ; PhD² ; Pé ; ter Faludi ; MD³ ; Jenny Han ; MS⁴ ; Leigh MacConell ; PhD⁴ ; Simone Wille ; MA¹ ; Jacek Kiljanski ; MD ; PhD¹
• 关键词：exenatide ; GLP-1 receptor agonist ; glucose control ; HbA1c ; hypoglycemia ; type 2 diabetes mellitus
• 刊名：Clinical Therapeutics
• 出版年：2012
• 期刊代码：65_01492918
• 类别：med
• 出版时间：June, 2012
• 卷：34
• 期：6
• 页码：1301-1313
• 文件大小：565 K

摘要

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 渭g 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 渭g 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] 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 鈭?.0%(0.10%) (P < 0.0001). In patients completing 52, 100, and 132 weeks, HbA_1c changes from baseline to end point were 鈭?.3%(0.10%), 鈭?.0%(0.12%), and 鈭?.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 鈭?.7 (0.39) kg and 鈭?.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 渭g 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. identifier: .