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OBJECTIVE- In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-I) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 rag) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks. RESEARCH DESIGN AND METHODS-- In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID→QW). A1C, fasting plasma glucose (FPG), body weight, blood pressure, fasting lipids, safety, and tolerability were assessed. RESULTS -- Patients continuing exenatide QW maintained A1C improvements through 52 weeks (least squares mean -2.0% [95% CI -2.1 to - 1.8%]). Patients switching from exenatide BID to exenatide QW achieved further A1C improvements; both groups exhibited the same A1C reduction and mean A1C (6.6%) at week 52. At week 52, 71 and 54% of all patients achieved A1C <7.0% and ≥6.5%, respectively. In both treatment arms, FPG was reduced by >40 mg/dl, and body weight was reduced by >4 kg after 52 weeks. Nausea occurred less frequently in this assessment period and was predominantly mild. No major hypoglycemia was observed. CONCLUSION -- Exenatide QW elicited sustained improvements in glycemic control and body weight through 52 weeks of treatment. Patients switching to exenatide QW experienced further improvements in A1C and FPG, with sustained weight loss. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- In patients with type 2 diabetes, exenatide reduces A1C, postprandial and fasting glucose, and weight. In this study we investigated the effects of continuous exenatide administration from a long-acting release (LAR) formulation. RESEARCH DESIGN AND METHODS -- In this randomized, placebo-controlled phase 2 study, exenatide LAR (0.8 or 2.0 mg) was administered subcutaneously once weekly for 15 weeks to subjects with type 2 diabetes (n = 45) suboptimally controlled with metformin (60%) and/or diet and exercise (40%): 40% female, A1C (mean ± SD) 8.5 ± 1.2%, fasting plasma glucose 9.9 ± 2.3 mmol/l, weight 106 ± 20 kg, and diabetes duration 5 ± 4 years. RESULTS -- From baseline to week 15, exenatide LAR reduced mean ± SE A1C by -1.4 ± 0.3% (0.8 mg) and - 1.7 ± 0.3% (2.0 mg), compared with +0.4 ± 0.3% with placebo LAR (P < 0.0001 for both). A1C of ≤7% was achieved by 36 and 86% of subjects receiving 0.8 and 2.0 mg exenatide LAR, respectively, compared with 0% of subjects receiving placebo LAR. Fasting plasma glucose was reduced by -2.4 ± 0.9 mmol/l (0.8 mg) and -2.2 ± 0.5 mmol/l (2.0 mg) compared with +1.0 ± 0.7 mmol/l with placebo LAR (P < 0.001 for both). Exenatide LAR reduced self-monitored postprandial hyperglycemia. Subjects receiving 2.0 mg exenatide LAR had body weight reductions (-3.8 ± 1.4 kg) (P < 0.05), whereas body weight was unchanged with both placebo LAR and the 0.8-mg dose. Mild nausea was the most frequent adverse event. No subjects treated with exenatide LAR withdrew from the study. CONCLUSIONS -- Exenatide LAR offers the potential of 24-h glycemic control and weight reduction with a novel once-weekly treatment for type 2 diabetes. [ABSTRACT FROM AUTHOR]

This study assessed whether glucose-dependent insulin secretion and overall counterregulatory response are preserved during hypoglycemia in the presence of exenatide. Twelve healthy fasted volunteers were randomized in a triple-blind crossover study to receive either intravenous exenatide (0.066 pmol. kg(-1). min(-1)) or placebo during a 270-min stepwise hyperinsulinemic-hypoglycemic clamp (insulin infusion 0.8 mU. kg(-1). min(-1)). Plasma glucose was clamped sequentially at 5.0 (0-120 min), 4.0 (120-180 min), 3.2 (180-240 min), and 2.7 mmol/l (240-270 min). At 270 min, insulin infusion was terminated and plasma glucose increased to approximately 3.2 mmol/l. The time to achieve plasma glucose >/=4 mmol/l thereafter was recorded. Insulin secretory rates (ISRs) and counterregulatory hormones were measured throughout. Glucose profiles were superimposable between the exenatide and placebo arms. In the presence of euglycemic hyperinsulinemia, ISRs in the exenatide arm were approximately 3.5-fold higher than in the placebo arm (353 +/- 29 vs. 100 +/- 29 pmol/min [least-square means +/- SE]). However, ISRs declined similarly and rapidly at all hypoglycemic steps (

The article offers information on an open-label randomized study which compared the efficacy of exenatide with insulin glargine titrated to glucose targets in lowering hemoglobin A1c. The study subjects, which involved adults with type 2 diabetes who had suboptimum glycaemic control, were randomly assigned to add exenatide or insulin glargine to their blood-glucose lowering regimens. Presented in details are the findings of the study. It concludes that exenatide is ideal for patients whose risk for hypoglycemia, weight loss and convenience are particular concerns.