Reitz Katherine M, Nassereldine Hasan, Kennedy Jason, Zeh Ryan, Khandwala Farah, Seymour Christopher W, Quintana Melanie, Viele Kert, Detry Michelle, Morris Alison, Methe Barbara, Zuckerbraun Brian, Girard Timothy D, Marroquin Oscar C, Esper Stephen, Holder-Murray Jennifer, Newman Anne B, Billiar Timothy R, Berry Scott, Angus Derek C, Neal Matthew D
From the Department of Surgery, University of Pittsburgh, Pittsburgh, PA.
Division of Vascular Surgery, University of Pittsburgh, Pittsburgh, PA.
Ann Surg Open. 2025 Apr 2;6(2):e566. doi: 10.1097/AS9.0000000000000566. eCollection 2025 Jun.
OBJECTIVE: In a randomized, embedded, multifactorial, adaptive platform (REMAP) trial, we hypothesized that perioperative metformin would improve postoperative time alive and out of the hospital, defined by 90-day hospital-free days (HFD-90), among nondiabetic aged adults. BACKGROUND: As our population ages, patients are increasingly frail requiring an emphasis on treatments to counteract their diminished resilience, especially following the stress of surgery. Growing literature supports metformin as an antiaging and anti-inflammatory therapy with beneficial effects extending into the perioperative period. METHODS: At-risk adults (≥60 years) scheduled for elective surgical interventions were randomized to placebo (N = √3) or metformin (N = 1:1:1; 500 mg:1000 mg:1500 mg) for short (7-28 days), intermediate (29-90 days), or long (>90 days) preoperative durations. An adaptive sample size of (N = 1000-2500) would identify at least a 15% improvement in HFD-90 for >1 metformin doses. Using intention-to-treat analysis, Bayesian ordinal logistic regression compared HFD-90 and frequentist logistic regression compared 90-day reoperation and readmission. RESULTS: Before trial closure, we randomized 302 (N = 106 placebo, N = 196 metformin [N = 64, 500 mg; N = 66, 1000 mg; and N = 66, 1500 mg]) patients without differences in baseline demographics (age 68 ± 6 years, 45% females, and 92% White race) or interventions (spine [29%], general [38%], colorectal [13%], and other [20%]). The odds of HFD-90 did not significantly differ between all doses and duration of metformin or placebo. There were no differences in the odds of reintervention (OR = 1.1 [95% CI, 0.6-2.0]) or readmission (OR = 1.5 [95% CI, 0.7-2.8]). CONCLUSIONS: Pretreatment with metformin did not improve postoperative outcomes in this REMAP trial, although trial enrollment was markedly limited by the COVID-19 pandemic and is underpowered.
目的:在一项随机、嵌入式、多因素、适应性平台(REMAP)试验中,我们假设围手术期使用二甲双胍可改善非糖尿病老年成人术后存活且未住院的时间,以90天无住院天数(HFD - 90)来定义。 背景:随着人口老龄化,患者日益虚弱,需要强调采取治疗措施来抵消其恢复力下降的问题,尤其是在手术应激之后。越来越多的文献支持二甲双胍作为一种抗衰老和抗炎疗法,其有益作用可延伸至围手术期。 方法:计划进行择期手术干预的高危成年人(≥60岁)被随机分为安慰剂组(N = √3)或二甲双胍组(N = 1:1:1;500毫克:1000毫克:1500毫克),术前用药时间分为短(7 - 28天)、中(29 - 90天)或长(>90天)。适应性样本量为(N = 1000 - 2500),对于超过1种二甲双胍剂量,将确定HFD - 90至少有15%的改善。采用意向性分析,贝叶斯序贯逻辑回归比较HFD - 90,频率主义逻辑回归比较90天再次手术和再入院情况。 结果:在试验结束前,我们随机分配了302例患者(N = 106例安慰剂组,N = 196例二甲双胍组 [N = 64例,500毫克;N = 66例,1000毫克;N = 66例,1500毫克]),他们在基线人口统计学特征(年龄68±6岁,45%为女性,92%为白人)或干预措施(脊柱手术[29%]、普通外科手术[38%]、结直肠手术[1,3%]和其他手术[20%])方面无差异。所有剂量和用药时间的二甲双胍组与安慰剂组在HFD - 90的几率上无显著差异。再次干预(比值比 = 1.1 [95%置信区间,0.6 - 2.0])或再入院(比值比 = 1.5 [95%置信区间,0.7 - 2.8])的几率也无差异。 结论:在这项REMAP试验中,二甲双胍预处理并未改善术后结局,尽管试验入组明显受到2019冠状病毒病大流行的限制且效能不足。
Cochrane Database Syst Rev. 2005-7-20
Cochrane Database Syst Rev. 2018-6-4
Cochrane Database Syst Rev. 2018-7-24
Cochrane Database Syst Rev. 2020-10-19
Cochrane Database Syst Rev. 2021-4-19
Cochrane Database Syst Rev. 2017-12-22
Cochrane Database Syst Rev. 2018-4-18
Cochrane Database Syst Rev. 2018-5-31
Cell. 2024-10-31
BMC Cardiovasc Disord. 2023-1-21
Signal Transduct Target Ther. 2022-12-16