Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial.
ABSTRACT Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A₁(c) (HbA₁(c)) targets.
To test whether twice-daily exenatide injections reduce HbA₁(c) levels more than placebo in people receiving insulin glargine.
Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA₁(c) level at site, performed from October 2008 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. (ClinicalTrials.gov registration number: NCT00765817)
59 centers in 5 countries.
Adults with type 2 diabetes and an HbA₁(c) level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents).
Assignment by a centralized, computer-generated, random-sequence interactive voice-response system to exenatide, 10 µg twice daily, or placebo for 30 weeks.
The primary outcome was change in HbA₁(c) level. Secondary outcomes included the percentage of participants with HbA₁(c) values of 7.0% or less and 6.5% or less, 7-point self-monitored glucose profiles, body weight, waist circumference, insulin dose, hypoglycemia, and adverse events.
112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study. The HbA₁(c) level decreased by 1.74% with exenatide and 1.04% with placebo (between-group difference, -0.69% [95% CI, -0.93% to -0.46%]; P < 0.001). Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo (between-group difference, -2.7 kg [CI, -3.7 to -1.7]). Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d. The estimated rate of minor hypoglycemia was similar between groups. Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events (P < 0.010); rates of nausea (41% vs. 8%), diarrhea (18% vs. 8%), vomiting (18% vs. 4%), headache (14% vs. 4%), and constipation (10% vs. 2%) were higher with exenatide than with placebo.
The study was of short duration. There were slight imbalances between groups at baseline in terms of sex, use of concomitant glucose-lowering medications, and HbA₁(c) levels, and more exenatide recipients than placebo recipients withdrew because of adverse events.
Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment. Adverse events of exenatide included nausea, diarrhea, vomiting, headache, and constipation.
Alliance of Eli Lilly and Company and Amylin Pharmaceuticals.
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ABSTRACT: The present short review summarizes and updates clinical experience with two classes of drugs introduced for the management of type 2 diabetes mellitus over the past 8 years: (i) the glucagon-like peptide-1 receptor agonists; and (ii) the dipeptidyl peptidase 4 inhibitors. Both classes of agents address the so called “incretin defect” in patients with T2DM. 摘要 这篇简短的综述总结与更新了在过去的8年中引进的两类2型糖尿病治疗药物的临床经验： (i)胰高血糖素样肽-1受体激动剂；以及(ii)二肽基肽酶4抑制剂。这两种类型的药物都是针对T2DM患者的“肠促胰岛素缺陷”。Journal of Diabetes 09/2013; 5(3). · 2.94 Impact Factor
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ABSTRACT: Traditional anti-diabetic drugs may have negative or positive effects on risk of bone fractures. Yet the relationship between the new class glucagon-like peptide-1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been established. We performed a meta-analysis including randomized controlled trials (RCT) to study the risk of bone fractures associated with liraglutide or exenatide, compared to placebo or other active drugs. We searched MEDLINE, EMBASE, and clinical trial registration websites for published or unpublished RCTs comparing the effects of liraglutide or exenatide with comparators. Only studies with disclosed bone fracture data were included. Separate pooled analysis was performed for liraglutide or exenatide, respectively, by calculating Mantel-Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206 patients. Liraglutide treatment was associated with a significant reduced risk of incident bone fractures (MH-OR = 0.38, 95 % CI 0.17-0.87); however, exenatide treatment was associated with an elevated risk of incident bone fractures (MH-OR = 2.09, 95 % CI 1.03-4.21). Publication bias and heterogeneity between studies were not observed. Our study demonstrated a divergent risk of bone fractures associated with different GLP-1 RA treatments. The current findings need to be confirmed by future well-designed prospective or RCT studies.Endocrine 07/2014; · 3.53 Impact Factor
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ABSTRACT: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in patients with type 2 diabetes. However, the effect on abdominal obesity has not yet been confirmed. The study aimed to systematically evaluate the effect of GLP-1RAs on waist circumference in patients with type 2 diabetes. MEDLINE, EMBASE, the Cochrane library and www.clinicaltrialgov were searched through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional anti-diabetic drugs with a duration ≥8 weeks. Weighted mean difference was estimated using random-effect model. Network meta-analysis was performed to supplement direct comparisons. Seventeen trials with 12 treatments were included. Overall, significant reductions on waist circumference following treatment of liraglutide-1.8 mg once daily (-5.24 cm, 95 % CI -7.68, -2.93), liraglutide-1.2 mg once daily (-4.73 cm, 95 % CI -6.68, -2.65) and exenatide-10 μg twice daily (-1.34 cm, 95 % CI -2.00, -0.75) were detected versus placebo. The reduction effect was more evident when compared with insulin and thiazolidinediones (range -1.71 to -8.03 cm). Compared with exenatide, liraglutide-0.6 mg once daily, taspoglutide, liraglutide-1.2 mg once daily and liraglutide-1.8 mg once daily significantly decreased waist circumference from -3.32 to -6.01 cm. Besides, liraglutide-1.8 mg once daily significantly decreased waist circumference by -1.73 cm (95 % CI -3.04, -0.55) versus sitagliptin, whereas no significant difference following liraglutide-1.2-mg-once-daily treatment was detected compared with liraglutide-1.8 mg once daily and sitagliptin. Reduction was observed with statistical significance for exenatide-10 μg twice daily compared with exenatide-5 μg twice daily (-1.21 cm, 95 % CI -2.43, -0.06). Ranking probability analysis indicated liraglutide-1.8 mg once daily and liraglutide-1.2 mg once daily decreased waist circumference most among all 12 treatments with probability of 98.36% and 91.82 %, respectively. Some GLP-1RAs, especially liraglutide-1.8 mg once daily and liraglutide-1.2 mg once daily, were associated with a significant reduction in waist circumference.Endocrine 08/2014; · 3.53 Impact Factor