Carol H Wysham1, Leigh A MacConell2, David G Maggs3, Ming Zhou4, Peter S Griffin3, Michael E Trautmann5. 1. Rockwood Clinic, Spokane, WA. Electronic address: cwysham@rockwoodclinic.com. 2. Amylin Pharmaceuticals/Bristol-Myers Squibb, San Diego, CA. 3. Amylin Pharmaceuticals, San Diego, CA. 4. Bristol-Myers Squibb, Hopewell, NJ. 5. Diabetes Research, Hamburg, Germany.
Abstract
OBJECTIVE: To evaluate the 5-year efficacy and safety of once weekly exenatide. PATIENTS AND METHODS: The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) randomized clinical trial consisted of a 30-week controlled phase (2 mg of exenatide once weekly vs 10 μg of exenatide twice daily) with an open-ended uncontrolled extension (once weekly exenatide only) in patients with type 2 diabetes mellitus on background glucose-lowering therapies (April 15, 2006, through February 21, 2012). At week 30, patients initially receiving 10 μg of exenatide twice daily switched to 2 mg of exenatide once weekly. Study end points included changes from baseline in hemoglobin A1c, fasting plasma glucose, weight, lipids, and blood pressure. Long-term safety data included adverse events, liver and renal function, and heart rate. RESULTS:Of 258 extension-phase patients, 153 (59.3%) completed 5 years of treatment. HemoglobinA1c levels were significantly and durably reduced from baseline (least-squares mean, -1.6%; 95% CI, -1.8% to -1.4%; vs -1.9% for exenatide once weekly at week 30), and 65 (43.9%) of 148 patients achieved hemoglobinA1c levels of less than 7.0%. Significant improvements in fasting plasma glucose level (-28.8 mg/dL; 95% CI, -36.2 to -21.5 mg/dL), weight (-3.0 kg; 95% CI, -4.6 to -1.3 kg), lipids, and diastolic blood pressure were observed, with minimal heart rate increase. Frequencies of nausea and injection-site reactions or nodules were decreased vs the initial 30-week controlled phase. Minor hypoglycemia occurred predominantly with sulfonylurea use, and no major hypoglycemia or new safety signals were observed. CONCLUSION: Long-term once weekly exenatide treatment was generally well tolerated with sustained glycemic improvement, weight reduction, and improved markers of cardiovascular risk in patients with type 2 diabetes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00308139.
RCT Entities:
OBJECTIVE: To evaluate the 5-year efficacy and safety of once weekly exenatide. PATIENTS AND METHODS: The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) randomized clinical trial consisted of a 30-week controlled phase (2 mg of exenatide once weekly vs 10 μg of exenatide twice daily) with an open-ended uncontrolled extension (once weekly exenatide only) in patients with type 2 diabetes mellitus on background glucose-lowering therapies (April 15, 2006, through February 21, 2012). At week 30, patients initially receiving 10 μg of exenatide twice daily switched to 2 mg of exenatide once weekly. Study end points included changes from baseline in hemoglobin A1c, fasting plasma glucose, weight, lipids, and blood pressure. Long-term safety data included adverse events, liver and renal function, and heart rate. RESULTS: Of 258 extension-phase patients, 153 (59.3%) completed 5 years of treatment. Hemoglobin A1c levels were significantly and durably reduced from baseline (least-squares mean, -1.6%; 95% CI, -1.8% to -1.4%; vs -1.9% for exenatide once weekly at week 30), and 65 (43.9%) of 148 patients achieved hemoglobin A1c levels of less than 7.0%. Significant improvements in fasting plasma glucose level (-28.8 mg/dL; 95% CI, -36.2 to -21.5 mg/dL), weight (-3.0 kg; 95% CI, -4.6 to -1.3 kg), lipids, and diastolic blood pressure were observed, with minimal heart rate increase. Frequencies of nausea and injection-site reactions or nodules were decreased vs the initial 30-week controlled phase. Minor hypoglycemia occurred predominantly with sulfonylurea use, and no major hypoglycemia or new safety signals were observed. CONCLUSION: Long-term once weekly exenatide treatment was generally well tolerated with sustained glycemic improvement, weight reduction, and improved markers of cardiovascular risk in patients with type 2 diabetes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00308139.
Authors: Carol H Wysham; Julio Rosenstock; Marion L Vetter; Fang Dong; Peter Öhman; Nayyar Iqbal Journal: Diabetes Obes Metab Date: 2017-08-22 Impact factor: 6.577
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