Effect of exenatide twice daily according to different meal schedules on glycemic control and variability in patients with type 2 diabetes mellitus (original) (raw)
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Diabetes Care, 2011
OBJECTIVE Hypoglycemia causes recurrent morbidity in patients with type 2 diabetes. This study evaluated if exenatide twice daily (BID) was noninferior to premixed insulin aspart 70/30 BID (PIA) for glycemic control and associated with less hypoglycemia. RESEARCH DESIGN AND METHODS In this open-label study, metformin-treated adults with type 2 diabetes were randomized to 26-week treatment with exenatide BID (4 weeks 5 μg, then 10 μg) or PIA. RESULTS Exenatide BID (n = 181) was noninferior to PIA (n = 173) for A1C control (least squares [LS] mean change −1.0 vs. −1.14%; difference [95% CI] 0.14 [−0.003 to 0.291]) and associated with a lower risk for hypoglycemia (8.0 vs. 20.5%, P < 0.05). LS mean weight decreased by 4.1 kg and increased by 1.0 kg with PIA (P < 0.001). A total of 39.2 vs. 20.8% of patients reached the composite end point of A1C <7.0%, no weight gain, and no hypoglycemia (P < 0.001; post hoc analysis). CONCLUSIONS In metformin-treated patients, exenatide BI...
2015
OBJECTIVE — This study evaluated the effects of exenatide, a novel incretin mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN AND METHODS — A 30-week, double-blind, placebo-controlled study was performed in 733 subjects (aged 55 10 years, BMI 33.6 5.7 kg/m2, A1C 8.5 1.0%; means SD) randomized to 5 g subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 g b.i.d. and arm B escalated to 10 g b.i.d. Subjects continued taking their dose of metformin and were randomized to either maximally effective (MAX) or minimum recommended (MIN) doses of sulfonylurea. RESULTS — Week 30 A1C changes from baseline (SE) were0.8 0.1 % (10g),0.6 0.1 % (5 g), and 0.2 0.1 % (placebo; adjusted P 0.0001 vs. placebo), yielding placebo-adjusted reductions of 1.0 % (10 g) and 0.8 % (5 g). In the evaluable population, ex-enatide-treated subjects were more likely t...
Effects of Exenatide Combined with Lifestyle Modification in Patients with Type 2 Diabetes
The American Journal of Medicine, 2010
To determine the effect of a lifestyle modification program plus exenatide versus lifestyle modification program plus placebo on weight loss in overweight or obese participants with type 2 diabetes treated with metformin and/or sulfonylurea. METHODS: In this 24-week, multicenter, randomized, double-blind, placebo-controlled study, 194 patients participated in a lifestyle modification program, consisting of goals of 600 kcal/day deficit and physical activity of at least 2.5 hours/week. Participants were randomized to 5 g exenatide twice daily injection ϩ lifestyle modification program (n ϭ 96) or placebo ϩ lifestyle modification program (n ϭ 98), and after 4 weeks increased their exenatide dose to 10 g twice daily or volume equivalent of placebo. RESULTS: Baseline characteristics: (mean Ϯ standard deviation) age, 54.8 Ϯ 9.5 years; weight, 95.5 Ϯ 16.0 kg; hemoglobin A 1c , 7.6 Ϯ 0.8%. At 24 weeks (least squares mean Ϯ standard error), treatments showed similar decreases in caloric intake (Ϫ378 Ϯ 58 vs Ϫ295 Ϯ 58 kcal/day, exenatide ϩ lifestyle modification program vs placebo ϩ lifestyle modification program, P ϭ .27) and increases in exercise-derived energy expenditure. Exenatide ϩ lifestyle modification program showed greater change in weight (Ϫ6.16 Ϯ 0.54 kg vs Ϫ3.97 Ϯ 0.52 kg, P ϭ .003), hemoglobin A 1c (Ϫ1.21 Ϯ 0.09% vs Ϫ0.73 Ϯ 0.09%, P Ͻ.0001), systolic (Ϫ9.44 Ϯ 1.40 vs Ϫ1.97 Ϯ 1.40 mm Hg, P Ͻ.001) and diastolic blood pressure (Ϫ2.22 Ϯ 1.00 vs 0.47 Ϯ 0.99 mm Hg, P ϭ .04). Nausea was reported more for exenatide ϩ lifestyle modification program than placebo ϩ lifestyle modification program (44.8% vs 19.4%, respectively, P Ͻ.001), with no difference in withdrawal rates due to adverse events (4.2% vs 5.1%, respectively, P ϭ 1.0) or rates of hypoglycemia. CONCLUSIONS: When combined with lifestyle modification, exenatide treatment led to significant weight loss, improved glycemic control, and decreased blood pressure compared with lifestyle modification alone in overweight or obese participants with type 2 diabetes on metformin and/or sulfonylurea treatment.
European Journal of Pharmacology, 2011
The aim of this study was to evaluate the effect of exenatide compared to glimepiride on body weight, glycemic control and insulin resistance in type 2 diabetic patients taking metformin. One hundred and eleven patients with uncontrolled type 2 diabetes mellitus and intolerant to metformin at the highest dosages (2500-3000 mg/day) were enrolled in this study. Patients were randomized to receive exenatide 5 μg twice a day or glimepiride 1 mg three times a day and titrated after 1 month to exenatide 10 μg twice a day or glimepiride 2 mg three times a day for 12 months in a randomized, single-blind, controlled study. We evaluated at the baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA 1c , glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR) index, adiponectin, tumor necrosis factor-α, and high sensitivity-C reactive protein. Both treatments gave a similar improvement of glycemic control, without any differences between the two groups. Only exenatide gave a decrease of BMI, insulin resistance parameters such as fasting plasma insulin, HOMA-IR, and adiponectin and a decrease of inflammatory parameters such as tumor necrosis factor-α, and high sensitivity-C reactive protein. Furthermore, the values obtained with exenatide were significantly better than the values recorded with glimepiride. We can conclude that exenatide was better than glimepiride in improving insulin resistance and inflammatory state. Furthermore, adiponectin increase, and tumor necrosis factor-α reduction seem to be related to weight loss obtained with exenatide.
Diabetes & Metabolism, 2010
The study objective was to analyze, in everyday practice, the long-term metabolic effects of exenatide (for 9 and 12 months) in patients with type 2 diabetes not responding to treatments with metformin and sulphonylurea at maximum dosages. A total of 299 type 2 diabetics were recruited from 14 centres specializing in diabetes care across Belgium. Main study endpoints were changes in HbA(1c), weight and waist circumference, and tolerability and compliance. Two patient cohorts were analyzed for effectiveness, with data available at 9 (n=90) and 12 (n=94) months of follow-up. Significant decreases in HbA(1c) of -1.3% and -1.6% were observed in the 9- and 12-month cohorts, respectively (P<0.001). The decrease in HbA(1c) was greater in patients with higher baseline levels (P<0.001), and the response was independent of baseline weight, body mass index (BMI), age, gender and diabetes duration. A progressive reduction of weight (4.9 kg) was also observed in the two cohorts at 9 and 12 months (P<0.001), with greater weight loss in patients with higher baseline BMI (P=0.046) and in female subjects (P=0.025). Waist circumference also decreased from baseline to endpoints. A correlation was observed between reduction in HbA(1c) and weight loss (P=0.019). Side effects, mainly of gastrointestinal origin, were reported in 33% (93/284 patients in the safety cohort). The rate of hypoglycaemia was 3.5%. Treatment was discontinued in 27% of patients (n=77) mainly due to drug inefficacy (53%, n=41) or adverse events (26%, n=20), or both (8%, n=6). Exenatide leads to long-term improvement of glycaemic control as well as weight loss in a majority of patients not responding to combined oral drug therapy in real-world clinical practice. However, no baseline factors predictive of response could be identified. Exenatide can be considered an effective treatment option in such patients, including those with high baseline HbA(1c) and long duration of diabetes.