McIntosh Brendan, Cameron Chris, Singh Sumeet R, Yu Changhua, Dolovich Lisa, Houlden Robyn
Canadian Agency for Drugs and Technologies in Health (CADTH), Ottawa, Ontario, Canada.
Open Med. 2012 Jun 4;6(2):e62-74. Print 2012.
Metformin and a sulphonylurea are often used in combination for the treatment of type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled with metformin and sulphonylurea combination therapy.
MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, BIOSIS Previews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published in English from 1980 to November 2009. Additional citations were obtained from the grey literature and conference proceedings and through stakeholder feedback. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. Key outcomes of interest were hemoglobin A1c, body weight, hypoglycemia, patients' satisfaction with treatment, quality of life, long-term diabetes-related complications, withdrawals due to adverse events, serious adverse events and mortality. Mixed-treatment comparison meta-analyses were conducted to calculate mean differences between drug classes for changes in hemoglobin A1c and body weight. When appropriate, pairwise meta-analyses were used to estimate differences for other outcomes.
We identified 33 randomized controlled trials meeting the inclusion criteria. The methodologic quality of the studies was generally poor. Insulins (basal, biphasic, bolus), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues and thiazolidinediones (TZDs) all produced statistically significant reductions in hemoglobin A1c in combination with metformin and a sulphonylurea (-0.89% to -1.17%), whereas meglitinides and alpha-glucosidase inhibitors did not. Biphasic insulin, bolus insulin, and TZDs were associated with weight gain (1.85-5.00 kg), whereas DPP-4 inhibitors and alpha-glucosidase inhibitors were weight-neutral, and GLP-1 analogues were associated with modest weight loss. Treatment regimens containing insulin were associated with increased hypoglycemia relative to comparators, but severe hypoglycemia was rare across all treatments.
Third-line agents for the treatment of type 2 diabetes are similar in terms of glycemic control but differ in their propensity to cause weight gain and hypoglycemia. Longer-term studies with larger sample sizes are required to determine if any of the drug classes are superior with regard to reducing diabetes-related complications.
二甲双胍和磺脲类药物常联合用于治疗2型糖尿病。我们进行了一项系统评价和荟萃分析，以评估在二甲双胍和磺脲类联合治疗血糖控制不佳的2型糖尿病患者中，所有可用类别的降糖治疗的相对安全性和疗效。
检索MEDLINE、MEDLINE在研及其他未索引引文、EMBASE、BIOSIS Previews、PubMed和Cochrane对照试验中央注册库，查找1980年至2009年11月以英文发表的随机对照试验。通过灰色文献、会议论文集以及利益相关者反馈获取其他引文。两名研究者独立选择研究、提取数据并评估偏倚风险。感兴趣的主要结局包括糖化血红蛋白、体重、低血糖、患者对治疗的满意度、生活质量、长期糖尿病相关并发症、因不良事件退出研究、严重不良事件和死亡率。进行混合治疗比较荟萃分析以计算各药物类别之间糖化血红蛋白和体重变化的平均差异。在适当情况下，采用成对荟萃分析估计其他结局的差异。
我们确定了33项符合纳入标准的随机对照试验。研究的方法学质量普遍较差。胰岛素（基础胰岛素、双相胰岛素、速效胰岛素）、二肽基肽酶-4（DPP-4）抑制剂、胰高血糖素样肽-1（GLP-1）类似物和噻唑烷二酮类（TZDs）与二甲双胍和磺脲类联合使用时，均使糖化血红蛋白有统计学意义的降低（-0.89%至-1.17%），而格列奈类和α-葡萄糖苷酶抑制剂则未降低。双相胰岛素、速效胰岛素和TZDs与体重增加相关（1.85 - 5.00千克），而DPP-4抑制剂和α-葡萄糖苷酶抑制剂对体重无影响，GLP-1类似物与适度体重减轻相关。与对照治疗相比，含胰岛素的治疗方案低血糖发生率增加，但所有治疗中严重低血糖均罕见。
2型糖尿病的三线治疗药物在血糖控制方面相似，但在导致体重增加和低血糖的倾向方面存在差异。需要进行更大样本量的长期研究，以确定是否有任何一类药物在降低糖尿病相关并发症方面更具优势。
