Diabetes Unit, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, University of Campania "Luigi Vanvitelli," Naples, Italy.
Medical Statistics Unit, University of Campania "Luigi Vanvitelli," Naples, Italy.
Diabetes Care. 2017 Apr;40(4):614-624. doi: 10.2337/dc16-1957.
The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes.
We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA, proportion of patients at HbA target ≤7% (53 mmol/mol), hypoglycemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI.
We identified 26 RCTs, lasting 12-52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA (WMD = -0.47%, 95% CI -0.59 to -0.35), more patients at HbA target (RR = 1.65, 95% CI 1.44-1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93-1.39) and a reduction in weight (WMD = -2.5 kg, 95% CI -3.3 to -1.7), with high heterogeneity ( > 89%, < 0.001) and a significant publication bias for three outcomes. In preplanned subgroup analyses, the combination treatment was similar to basal-bolus insulin regimens for glycemic control, with less hypoglycemia (RR = 0.66, 95% CI 0.46-0.93) and reduced weight (WMD = -4.7 kg, 95% CI -6.9 to -2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA WMD = -0.56%, 95% CI -0.72 to -0.40).
GLP-1RAs alone or as titratable fixed-ratio combinations with basal insulin may represent a promising option to advance basal insulin therapy or to initiate injectable therapy in patients with type 2 diabetes inadequately controlled on oral agents. Longer studies are needed to assess durability and tolerability.
基础胰岛素联合胰高血糖素样肽 1 受体激动剂（GLP-1RA）的联合治疗方案已被提议作为强化 2 型糖尿病胰岛素治疗的一种选择。我们对比较这种联合治疗策略与其他注射用抗糖尿病药物在 2 型糖尿病成年患者代谢控制方面的随机对照试验（RCT）进行了荟萃分析。
我们在多个电子数据库中进行了电子检索，检索截至 2016 年 11 月，以确定评估 HbA、HbA 达标患者比例（HbA 目标≤7%[53mmol/mol]）、低血糖和体重变化的 RCT。我们使用随机效应模型计算加权均数差（WMD）或相对风险（RR）及其 95%置信区间。
我们确定了 26 项 RCT，持续 12-52 周，涉及 11425 名患者。当联合治疗策略与其他注射用治疗（总体数据）相比时，HbA 降低（WMD=-0.47%，95%CI-0.59 至-0.35），HbA 达标患者比例增加（RR=1.65，95%CI 1.44-1.88），低血糖事件相似（RR=1.14，95%CI 0.93-1.39），体重减轻（WMD=-2.5kg，95%CI-3.3 至-1.7），异质性高（>89%，<0.001），三个结局存在显著发表偏倚。在预先计划的亚组分析中，联合治疗与基础-餐时胰岛素方案在血糖控制方面相似，低血糖发生率较低（RR=0.66，95%CI 0.46-0.93），体重减轻（WMD=-4.7kg，95%CI-6.9 至-2.4）。固定比例联合治疗的结果与总体分析相似（HbA WMD=-0.56%，95%CI-0.72 至-0.40）。
GLP-1RA 单独使用或与基础胰岛素联合作为可滴定固定比例联合治疗，可能是一种有前途的选择，可以推进基础胰岛素治疗，或在口服药物治疗控制不佳的 2 型糖尿病患者中开始注射用治疗。需要更长时间的研究来评估其持久性和耐受性。
