Heckman-Stoddard Brandy M, Crandall Jill P, Edelstein Sharon L, Prorok Philip C, Dabelea Dana, Hamman Richard, Hazuda Helen P, Horton Edward, Hoskin Mary A, Perloff Marjorie, Bowers Anna, Knowler William C, Ford Leslie G, Temprosa Marinella
National Cancer Institute, Rockville, MD, United States.
Albert Einstein College of Medicine, Bronx, NY, United States.
Cancer Prev Res (Phila). 2025 Apr 17. doi: 10.1158/1940-6207.CAPR-23-0461.
Meta-analyses have reported a decrease in overall cancer incidence of approximately 10-40% with metformin use among individuals with diabetes. Lifestyle change could potentially reduce cancer incidence. The objective was to determine whether metformin or intensive lifestyle intervention (ILS) reduces the risk of cancer among adults at high risk of diabetes. The Diabetes Prevention Program (DPP, 1996-2001) randomized 3234 participants to ILS, metformin (850 mg twice daily), or blinded placebo. During follow-up through the DPP Outcomes Study (DPPOS), all participants were offered a modified lifestyle intervention, and metformin continued open-label metformin group. Participants reported cancer cases annually. Medical records were adjudicated for all reported events. The primary endpoint was total cancer incidence, comparing metformin versus placebo, with ILS versus placebo as a secondary objective. After a median follow-up of 21 years, 546 participants (173 metformin, 182 ILS, and 191 placebo) were diagnosed with a first incident cancer. Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a hazard ratio (HR) of 0.90 (95%CI = 0.73 to 1.10) for metformin compared to placebo and 0.96 (95%CI = 0.79 to 1.18) for ILS compared to placebo. There were no differences between any treatment groups for obesity-related cancer or in sex-specific analyses. Neither assignment to metformin nor ILS reduced cancer incidence among adults at high risk of diabetes. These results may be impacted by increased non-study metformin usage over time due to the development of diabetes and reduced intensity of ILS intervention over time.
荟萃分析报告称，糖尿病患者使用二甲双胍后，总体癌症发病率下降了约10%-40%。生活方式的改变可能会降低癌症发病率。目的是确定二甲双胍或强化生活方式干预（ILS）是否能降低糖尿病高危成年人患癌症的风险。糖尿病预防计划（DPP，1996-2001年）将3234名参与者随机分为ILS组、二甲双胍组（每日两次，每次850毫克）或盲法安慰剂组。在糖尿病预防计划结局研究（DPPOS）的随访期间，所有参与者都接受了改良的生活方式干预，二甲双胍组继续使用开放标签的二甲双胍。参与者每年报告癌症病例。对所有报告的事件进行医疗记录判定。主要终点是总癌症发病率，比较二甲双胍与安慰剂，以ILS与安慰剂作为次要目标。中位随访21年后，546名参与者（173名二甲双胍组、182名ILS组和191名安慰剂组）被诊断为首次发生癌症。二甲双胍组、ILS组和安慰剂组的癌症发病率分别为每1000人年9.8、10.5和10.8例，二甲双胍组与安慰剂组相比的风险比（HR）为0.90（95%CI=0.73至1.10），ILS组与安慰剂组相比的风险比为0.96（95%CI=0.79至1.18）。在肥胖相关癌症或按性别分析中，任何治疗组之间均无差异。对于糖尿病高危成年人，使用二甲双胍或ILS均未降低癌症发病率。随着时间的推移，由于糖尿病的发展，非研究性二甲双胍的使用增加，以及随着时间的推移ILS干预强度降低，这些结果可能会受到影响。
