The Johns Hopkins University School of Medicine and The Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Baltimore, MD 21205, USA.
Ann Intern Med. 2011 May 3;154(9):602-13. doi: 10.7326/0003-4819-154-9-201105030-00336. Epub 2011 Mar 14.
Given the increase in medications for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices.
To summarize the benefits and harms of metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists, as monotherapy and in combination, to treat adults with type 2 diabetes.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through April 2010 for English-language observational studies and trials. The MEDLINE search was updated to December 2010 for long-term clinical outcomes.
Two reviewers independently screened reports and identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms.
Two reviewers following standardized protocols serially extracted data, assessed applicability, and independently evaluated study quality.
Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A(1c) level by about 1 percentage point and most 2-drug combinations produced similar reductions. Metformin was more efficacious than the DPP-4 inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about -2.5 kg. Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones.
Only English-language publications were reviewed. Some studies may have selectively reported outcomes. Many studies were small, were of short duration, and had limited ability to assess clinically important harms and benefits.
Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A(1c) levels, but some increased risk for hypoglycemia and other adverse events.
Agency for Healthcare Research and Quality.
随着 2 型糖尿病治疗药物的增加，临床医生和患者需要了解这些药物的疗效和安全性，以便做出明智的选择。
总结二甲双胍、第二代磺酰脲类、噻唑烷二酮类、格列奈类、二肽基肽酶-4（DPP-4）抑制剂和胰高血糖素样肽-1 受体激动剂作为单药和联合治疗 2 型糖尿病成人患者的疗效和安全性。
从建库到 2010 年 4 月，我们通过 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册库检索了英语文献，并检索了关于单药治疗或联合治疗的长期临床结局的观察性研究和试验。2010 年 12 月，我们更新了 MEDLINE 检索，以获取长期临床结局的数据。
两名评审员独立筛选报告，并确定了 140 项比较单药或联合治疗的头对头比较试验和 26 项观察性研究，这些研究报告了中间或长期的临床结局或不良事件。
两名评审员遵循标准化方案，连续提取数据、评估适用性，并独立评估研究质量。
关于长期临床结局（全因死亡率、心血管疾病、肾病和神经病变）的证据质量较低或不足。大多数药物可使糖化血红蛋白水平降低约 1%，大多数 2 种药物联合治疗可产生类似的降低效果。二甲双胍比 DPP-4 抑制剂更有效，与噻唑烷二酮类或磺酰脲类相比，体重的平均差异约为 2.5 公斤。与吡格列酮、磺酰脲类和 DPP-4 抑制剂相比，二甲双胍可降低低密度脂蛋白胆固醇水平。与单用二甲双胍相比，磺酰脲类药物发生轻度或中度低血糖的风险增加 4 倍，与二甲双胍联合使用时，发生低血糖的风险增加 5 倍以上，与二甲双胍联合使用时，发生低血糖的风险增加 5 倍以上。与磺酰脲类药物相比，噻唑烷二酮类药物增加了充血性心力衰竭的风险，与二甲双胍相比，增加了骨折的风险。与噻唑烷二酮类药物相比，二甲双胍更易引起腹泻。
仅对英语文献进行了回顾。一些研究可能有选择性地报告了结果。许多研究规模较小、持续时间较短，且评估临床重要疗效和安全性的能力有限。
有证据支持二甲双胍作为治疗 2 型糖尿病的一线药物。大多数 2 种药物联合治疗可同样降低糖化血红蛋白水平，但某些药物会增加低血糖和其他不良事件的风险。
美国医疗保健研究与质量局。
