Background/Objectives

Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed.

Subjects/Methods

After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR.

Results

Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 – 17.9), BMI 31.2 (22.3 – 45.1), HOMA-IR 3.4 (0.2 – 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (−2.1 to +5.1)). For HOMA-IR, a decrease was observed (−1.1 (−4.6 to +1.4)).

Conclusion

While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.

中文翻译：

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肥胖和胰岛素抵抗青少年的长期二甲双胍治疗，开放标签扩展研究的结果

背景/目标

如今，标签外的二甲双胍经常用于治疗青少年肥胖症。但是，关于肥胖青少年中长期使用二甲双胍治疗的研究很少。因此，在一项为期18个月的随机安慰剂对照试验（RCT）之后，进行了一项18个月的开放标签延伸研究，该试验针对肥胖和胰岛素抵抗青少年中的二甲双胍的疗效，安全性和耐受性。

学科/方法

RCT完成后，向所有参与者提供二甲双胍，其体重指数标准偏差评分（BMI-sds）> 2.3，并且胰岛素抵抗稳态模型评估（HOMA-IR）≥3.4。终点是BMI和HOMA-IR的变化。

结果

总体而言，有31/42名参与者完成了扩展研究（74％的女孩，中位年龄14.8（11.6-17.9），BMI 31.2（22.3-45.1），HOMA-IR 3.4（0.2-8.8））。开始时，有22/42（52.4％）名参与者符合二甲双胍的治疗资格，其中13名（59.0％）同意接受治疗。在继续服用二甲双胍的受试者中，观察到BMI（+2.2（+0.2至+9.0））和HOMA-IR（+13.7（+1.6至+48.3））升高。在初次服用二甲双胍的受试者中，BMI在最初下降后稳定（+0.5（-2.1至+5.1））。对于HOMA-IR，观察到下降（-1.1（-4.6至+1.4））。

结论

虽然在未接受二甲双胍治疗的患者中服用二甲双胍似乎会导致BMI和HOMA-IR的初始下降，但没有证据表明在青少年中长期使用后能持续产生疗效。依从性有限和/或剂量不足可能解释了青少年和成人之间长期影响的差异。