Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
Ann Intern Med. 2011 May 17;154(10):672-9. doi: 10.7326/0003-4819-154-10-201105170-00007.
Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea.
To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea.
MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases.
Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea.
Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia.
Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents.
Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions.
There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics.
Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacăo de Aperfeicoamento de Pessoal de Nível Superior.
在使用二甲双胍和磺酰脲类药物控制血糖不理想的情况下，很少有研究探讨加用第三种降血糖药物的效果。
比较加用第三种降血糖药物治疗二甲双胍和磺酰脲类药物控制不佳的 2 型糖尿病患者的疗效。
MEDLINE、EMBASE、Cochrane 图书馆、LILACS 和 ClinicalTrials.gov 电子数据库。
至少持续 24 周的随机试验。研究评估了在接受二甲双胍和磺酰脲类药物联合治疗、糖化血红蛋白（HbA1c）水平大于 7.0%且年龄在 18 岁或以上的 2 型糖尿病患者中，加用第三种降血糖药物对治疗的影响。
主要终点为 HbA1c 水平变化、体重变化和严重低血糖发生频率。
共纳入 18 项涉及 4535 名参与者的试验，平均持续时间为 31.3 周（24-52 周）。与安慰剂相比，药物类别在 HbA1c 水平（阿卡波糖的降幅为-0.70%[95%可信区间{CrI}，-1.33%至-0.08%]至胰岛素的-1.08%[CrI，-1.41%至-0.77%]）方面无差异。胰岛素可导致体重增加（2.84kg[CrI，1.76-3.90kg]）和噻唑烷二酮类药物（4.25kg[CrI，2.76-5.66kg]），而胰高血糖素样肽-1 激动剂可导致体重减轻（-1.63kg[CrI，-2.71-0.60kg]）。胰岛素导致的严重低血糖发作绝对次数是其他非胰岛素类降糖药物的两倍。
大多数试验都是短期的，试验质量参差不齐。由于相对于降血糖药物的试验较少，研究人员依赖间接比较，这增加了研究结果和结论的不确定性。
对于已经接受二甲双胍和磺酰脲类药物治疗的 2 型糖尿病患者，加用第三种药物治疗时，药物类别之间的获益无明显差异。最合适的选择应取决于每个患者的临床特征。
巴西国家科学技术发展理事会和高级人员培训协调委员会。
