Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study.
Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study.
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DOI：
10.2337/dc11-1299
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发表时间：
2012-04
期刊：
影响因子：
16.2
通讯作者：
Diabetes Prevention Program Research Group
中科院分区：
文献类型：
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作者：
Diabetes Prevention Program Research Group
在糖尿病预防计划（DPP）中，二甲双胍可以减轻体重，延缓或预防糖尿病。我们检查了其长期的安全性和耐受性，沿着体重减轻，以及DPP期间腰围的变化及其长期随访。二甲双胍或安慰剂的随机双盲临床试验，随后进行7-8年的开放标签扩展，并分析不良事件，耐受性以及依从性对体重和腰围变化的影响。未发现重大安全性问题。二甲双胍组的胃肠道症状比安慰剂组更常见，并随时间推移而下降。DPP期间，二甲双胍组的平均血红蛋白和红细胞压积水平略低于安慰剂组。二甲双胍组的血红蛋白和红细胞压积下降发生在随机化后的第一年，随着时间的推移没有观察到进一步的变化。在DPP治疗期间，二甲双胍组受试者的体重和腰围较安慰剂组降低（二甲双胍组体重降低2.06 ± 5.65% vs. 0.02 ± 5.52%，P < 0.001，腰围降低2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm，P < 0.001）。2年双盲期内体重减轻的幅度与依从性直接相关（P < 0.001）。在整个非盲随访期间，二甲双胍组的体重减轻仍显著大于安慰剂组（2.0% vs. 0.2%，P < 0.001），这与二甲双胍的持续依从性程度有关（P < 0.001）。用于预防糖尿病的二甲双胍是安全的，耐受性良好。体重减轻与二甲双胍的依从性有关，并可持续至少10年的治疗。
Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. The randomized double-blind clinical trial of metformin or placebo followed by a 7–8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference. No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001). Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.