第49届欧洲糖尿病研究协会年会(EASD2013)于9月23-27日在西班牙巴塞罗那召开。当地时间9月24日上午，在“GLP-1受体激动剂的个体化选择(Individualising
the choice among GLP-1 receptor
agonists)”专场上，百时美施贵宝美国研发中心Jaret Malloy博士报告的一项多中心随访研究（DURATION 3研究）证实，对正在使用
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| Jaret Malloy博士 |
DURATION 3研究是一项开放标签、随机、对照试验，随访时间超过3年，比较了每周一次、固定剂量配方的GLP-1受体激动剂艾塞那肽（EQW，商品名：
研究人员通过26周的初步研究进一步筛选患者，继续治疗至156周。甘精胰岛素组的胰岛素用量根据采用INITIATE研究规则计算。HbA1c得到控制定义为治疗26周后，HbA1c达标且保持HbA1c ≤7%（53 mmol/mol）。HbA1c控制不佳或未达标定义为治疗26周后，两次连续随访（间隔10至12周）时HbA1c >7%，或任意一次随访时HbA1c >9%。
接受艾塞那肽治疗的患者233例，接受甘精胰岛素治疗的患者223 例。基线特征（EQW vs. IG）分别为：平均年龄（57 vs.58岁），男性比率（52% vs.55%），糖尿病病程（均为8年），平均糖化血红蛋白（均为8.3％）。在两个治疗组中，70％的患者仅使用二甲双胍（MET），30％使用二甲双胍和一种磺脲类药物。在治疗过程中，平均每日胰岛素剂量逐渐增加，基线时10 IU，26周时31 IU，3年时达到39 IU。艾塞那肽治疗组完成3年随访治疗的患者人数百分率为43%，在最后随访结束时HbA1c得到控制率为50%，均高于甘精胰岛素治疗组（分别为33%和43%）。且艾塞那肽治疗组HbA1c得到控制的持续时间为25个月，比甘精胰岛素治疗组（16.7个月）要长。治疗3年以上HbA1c控制失败的危险比为1.4（IG / EQW）。
相比甘精胰岛素治疗组，艾塞那肽治疗组的HbA1c降低幅度更大（-1.17％ vs. -1.32％），空腹血糖下降幅度更大（-3.07 vs. -2.28mmol/L），体重减轻更多（+0.70 vs. -3.44kg），低血糖事件发生率更低（3.1 vs. 1.1例/年），但艾塞那肽治疗组的恶心（2％ vs. 18％）和
研究摘要：
| Sustaining HbA1c control over three years during treatment with exenatide once weekly compared with insulin glargine (比较艾塞那肽每周一次和甘精胰岛素在3年以上的治疗过程中对HbA1c的持续控制能力) |
| Background and aims: The DURATION 3 study was an open-label, randomised, controlled trial of patients with T2DM comparing the once-weekly fixed-dose formulation of the GLP-1 receptor agonist exenatide (EQW) with titrated insulin glargine (IG) over 3 years. Sustained glucose control is difficult to achieve due to the progressive deterioration of insulin secretion over time requiring therapy escalation. These additional analyses assessed the comparative abilities of EQW vs IG to sustain HbA1c control as defined below. Materials and methods: Patients were followed through a 26-week core study with an option to continue treatment up to 156 weeks. Dosage for the IG group was determined by the Initiate Insulin by Aggressive Titration and Education (INITIATE) algorithm. HbA1c control was defined as achieving and maintaining an HbA1c ≤7% (53 mmol/mol) after 26 weeks of treatment. Loss of, or failure to achieve, HbA1c control was defined as an HbA1c >7% at two consecutive visits (10 to 12 weeks apart) or an HbA1c >9% at one visit after 26 weeks of treatment. Results: The intent-to-treat (ITT) population comprised 233 EQW and 223 IG patients. Baseline characteristics (EQW vs IG) included mean age (57 vs 58 years), % male (52 vs 55), mean duration of diabetes (both 8 years), and mean HbA1c(both 8.3%). Within both treatment groups 70% of patients were taking metformin (MET) alone and 30% were taking MET and a sulfonylurea. Mean daily insulin dose increased from baseline 10 IU to 31 IU at Week 26 and 39 IU at Year 3. Of the enrolled participants, 140 EQW and 147 IG patients completed 3 years in their original treatment groups. Within the ITT population, a greater percentage of EQW patients achieved and sustained HbA1c control until last visit (50%) compared with IG patients (43%). Similarly, a higher percentage of EQW 3-year completers (43%) demonstrated HbA1c control through 3 years compared with IG patients (33%). EQW ITT patients had a longer period of HbA1c control. The median time of control was 25.0 months for EQW patients and 16.7 months for IG patients (Kaplan-Meier estimates P=0.03 from Wilcoxon test). The ITT population hazard ratio of failure in control over 3 years was 1.4 (IG/EQW, P=0.006 from Cox proportional hazard model). Among ITT patients with HbA1c control until last visit the following results were observed. Greater HbA1c reduction was observed in EQW (LS mean = -1.32%) compared with IG (-1.17%; 95% CI difference = -0.34, 0.04, P=0.12). EQW patients exhibited less reduction (LS mean = -2.28 mmol/l) in fasting serum glucose compared with IG patients (-3.07; 95% CI difference = 0.03, 1.54, P=0.04) and greater weight loss than IG patients (LS mean = -3.44 kg vs +0.70, respectively (95% CI difference = -5.71, -2.56, P<.0001). EQW patients demonstrated less hypoglycaemia (event rate per year 1.1) than IG (3.1). EQW patients reported greater nausea and diarrhoea than IG patients with EQW patients reporting 18% nausea and 15% diarrhoea and IG patients reporting 2% nausea and 4% diarrhoea. Conclusion: Throughout the 3-year trial of EQW vs IG a greater number of EQW patients achieved and sustained HbA1ccontrol with greater weight reduction and less hypoglycaemia compared with IG patients, despite continued insulin up titration. |
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