Diabetology, Careggi Hospital and University of Florence, Italy.
Diabetes Centre District 3, Azienda Sanitaria Universitaria Integrata di Trieste, Via Puccini 48/50, 34100, Trieste, Italy.
Nutr Metab Cardiovasc Dis. 2021 Mar 10;31(3):699-704. doi: 10.1016/j.numecd.2020.11.031. Epub 2020 Dec 10.
The Italian Society of Diabetology and the Italian Association of Clinical Diabetologists are developing new guidelines for drug treatment of type 2 diabetes. The effects of anti-hyperglycaemic drugs on all-cause mortality and major adverse cardiovascular events (MACEs) were included among the critical clinical outcomes. We have therefore carried out an updated meta-analysis on the effects of metformin on these outcomes.
A MEDLINE and EMBASE search was performed to identify all randomized controlled trials (RCTs) with duration ≥52 weeks (published up to August 2020), in which metformin was compared with either placebo/no therapy or active comparators. MACEs (restricted for RCT reporting MACEs within their study endpoints) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified endpoints) were considered as the primary endpoints. Mantel-Haenszel odds ratio (MH-OR) with 95% confidence interval was calculated for all endpoints considered. Metformin was associated with a nonsignificant reduction of all-cause mortality (n = 13 RCTs; MH-OR 0.80 [95% CI 0.60, 1.07]). However, this association became statistically significant after excluding RCTs comparing metformin with sulfonylureas, SGLT-2 inhibitors or GLP-1 analogues (MH-OR 0.71 [0.51, 0.99]). Metformin was associated with a lower risk of MACEs compared with comparator treatments (n = 2 RCTs; MH-OR 0.52 [0.37, 0.73]), p < 0.001. Similar results were obtained in a post-hoc analysis including all RCTs fulfilling criteria for inclusion in the analysis (MH-OR: 0.57 [0.42, 0.76]).
This updated meta-analysis suggests that metfomin is significantly associated with lower risk of MACEs and tendentially lower all-cause mortality compared to placebo or other anti-hyperglycaemic drugs.
意大利糖尿病学会和意大利临床糖尿病学会正在制定 2 型糖尿病药物治疗新指南。降血糖药物对全因死亡率和主要不良心血管事件（MACE）的影响被列为关键临床结局。因此，我们对二甲双胍在这些结局方面的效果进行了更新的荟萃分析。
对 MEDLINE 和 EMBASE 进行了检索，以确定所有持续时间≥52 周的随机对照试验（RCT）（截至 2020 年 8 月发布），其中将二甲双胍与安慰剂/无治疗或活性对照进行比较。MACE（仅限于在研究终点内报告 MACE 的 RCT）和全因死亡率（无论是否将 MACE 纳入预先指定的终点）被视为主要终点。对所有考虑的终点均计算 Mantel-Haenszel 比值比（MH-OR）及其 95%置信区间。
二甲双胍与全因死亡率呈非显著降低相关（n=13 RCT；MH-OR 0.80 [95% CI 0.60, 1.07]）。然而，在排除比较二甲双胍与磺酰脲类药物、SGLT-2 抑制剂或 GLP-1 类似物的 RCT 后，这种关联具有统计学意义（MH-OR 0.71 [0.51, 0.99]）。与对照治疗相比，二甲双胍与较低的 MACE 风险相关（n=2 RCT；MH-OR 0.52 [0.37, 0.73]），p<0.001。在纳入分析的所有 RCT 进行事后分析中也得到了类似的结果（MH-OR：0.57 [0.42, 0.76]）。
这项更新的荟萃分析表明，与安慰剂或其他降血糖药物相比，二甲双胍与 MACE 风险降低显著相关，且全因死亡率有降低趋势。
