Tsironikos Georgios I, Tsolaki Vasiliki, Zakynthinos George E, Rammou Vasiliki, Kyprianidou Despoina, Antonogiannis Thomas, Zakynthinos Epaminondas, Bargiota Alexandra
Department of Research for General Medicine and Primary Health Care, Faculty of Medicine, University of Ioannina, Ioannina, University Campus, 45110 Ioannina, Greece.
Department of Critical Care, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Mezourlo, 41335 Larissa, Greece.
J Clin Med. 2025 Jul 12;14(14):4947. doi: 10.3390/jcm14144947.
The effectiveness of metformin in preventing Type-2 Diabetes Mellitus (T2DM) is examined. There are new available data. Currently, there are no available analyses classifying its effectiveness compared to placebo, standard care, or lifestyle interventions, and there is limited evidence on the combined action of metformin and lifestyle interventions in preventing T2DM. To calculate the updated overall effectiveness of metformin in preventing T2DM using all available and most recent data, and to explore the effectiveness of metformin and lifestyle interventions in preventing T2DM. A search was performed in PubMed and the Cochrane Library Central Register of Controlled Trials (CENTRAL) (from inception to 24 May 2025). A systematic review (SR) and meta-analysis (MA) of randomized controlled trials (RCTs) was carried out, including metformin-naïve adults with any identified diabetes risk factors. The overall effectiveness of metformin was estimated by combining studies that compare metformin against placebo, metformin and standard care against standard care, and metformin plus lifestyle interventions and the same lifestyle interventions. The combined action of metformin and lifestyle interventions was evaluated against standard care. We performed a GRADE assessment of the overall evidence. Overall, metformin may reduce the incidence of T2DM by 23% in high-risk adults (OR 0.77, 95% CI 0.67, 0.88, -value 0.0001) and 25% in patients with prediabetes (OR 0.75, 95%CI 0.66, 0.86, -value < 0.0001). It is also effective in both obese and normal-weight patients, in Caucasians, in studies with female predominance, in studies with a mean age over 60 years, at 1700 mg daily, and after 18 months of administration. Effectiveness weakens after interruption of administration. Metformin is more effective compared to placebo and when combined with standard care than standard care alone, but not when combined with lifestyle interventions against lifestyle interventions alone. Metformin and lifestyle interventions reduce the incidence of diabetes in patients with prediabetes by 52% compared to standard care (OR 0.48, 95% CI 0.30, 0.77; -value 0.002). There are effectiveness concerns in studies with more men than women, Asian Indians and Pakistanis, a mean age below 60 years, 500 mg of metformin daily, and after six months. The effect is reduced during post-intervention. Finally, metformin alone is more effective than standard care (OR 0.56, 95% CI 0.34, 0.90, -value 0.02). The quality of evidence was moderate for the overall effectiveness of metformin and metformin combined with lifestyle interventions, and low for metformin against standard care. A 1700 mg dose of metformin daily is effective in preventing T2DM, especially in Caucasians, in women over 60 years, in prediabetes, and independent of obesity. Lifestyle interventions and 500 mg of metformin daily may prevent T2DM in patients with prediabetes, especially in men and Asian Indians or Pakistanis under 60 years. The effectiveness of complex interventions is more pronounced than that of metformin alone in patients with prediabetes. Further research is needed for post-intervention effectiveness, patients with any diabetes risk factors, patients from different regions, and women in complex interventions.
研究了二甲双胍预防2型糖尿病（T2DM）的有效性。有新的可用数据。目前，尚无将其与安慰剂、标准治疗或生活方式干预进行有效性分类的分析，且关于二甲双胍与生活方式干预联合预防T2DM的证据有限。为了使用所有可用的最新数据计算二甲双胍预防T2DM的最新总体有效性，并探讨二甲双胍和生活方式干预预防T2DM的有效性。在PubMed和Cochrane图书馆对照试验中央注册库（CENTRAL）（从创刊到2025年5月24日）进行了检索。对随机对照试验（RCT）进行了系统评价（SR）和荟萃分析（MA），纳入了所有未使用过二甲双胍且有任何已确定糖尿病风险因素的成年人。通过合并比较二甲双胍与安慰剂、二甲双胍加标准治疗与标准治疗、二甲双胍加生活方式干预与相同生活方式干预的研究来估计二甲双胍的总体有效性。评估了二甲双胍与生活方式干预的联合作用与标准治疗的比较。我们对总体证据进行了GRADE评估。总体而言，二甲双胍可能使高危成年人的T2DM发病率降低23%（OR 0.77，95%CI 0.67，0.88，P值0.0001），使糖尿病前期患者的发病率降低25%（OR 0.75，95%CI 0.66，0.86，P值<0.0001）。它在肥胖和正常体重患者、白种人、女性占主导的研究、平均年龄超过60岁的研究、每日1700毫克以及给药18个月后均有效。停药后有效性减弱。与安慰剂相比以及与标准治疗联合使用时，二甲双胍比单独使用标准治疗更有效，但与生活方式干预联合使用时并不比单独的生活方式干预更有效。与标准治疗相比，二甲双胍和生活方式干预可使糖尿病前期患者的糖尿病发病率降低52%（OR 0.48，95%CI 0.30，0.77；P值0.002）。在男性多于女性、亚洲印度人和巴基斯坦人、平均年龄低于60岁、每日500毫克二甲双胍以及六个月后的研究中，存在有效性问题。干预后效果会降低。最后，单独使用二甲双胍比标准治疗更有效（OR 0.56，95%CI 0.34，0.90，P值0.02）。二甲双胍及其与生活方式干预联合使用的总体有效性的证据质量为中等，二甲双胍与标准治疗比较的证据质量为低等。每日1700毫克剂量的二甲双胍在预防T2DM方面有效，尤其是在白种人、60岁以上女性、糖尿病前期患者中，且与肥胖无关。生活方式干预和每日500毫克二甲双胍可能预防糖尿病前期患者的T2DM，尤其是60岁以下的男性以及亚洲印度人或巴基斯坦人。在糖尿病前期患者中，综合干预的有效性比单独使用二甲双胍更显著。对于干预后有效性、有任何糖尿病风险因素的患者、不同地区的患者以及综合干预中的女性，还需要进一步研究。
