Metformin may exert anticancer effects through indirect (mediated by metabolic changes) or direct mechanisms. The goal was to examine metformin impact on metabolic factors in non-diabetic subjects and determine whether this impact varies by baseline BMI, insulin, and rs11212617 SNP in CCTG MA.32, a double-blind placebo-controlled randomized adjuvant breast cancer (BC) trial. 3649 subjects with T1-3, N0-3, M0 BC were randomized; pretreatment and 6-month on-treatment fasting plasma was centrally assayed for insulin, leptin, highly sensitive C-reactive protein (hsCRP). Glucose was measured locally and homeostasis model assessment (HOMA) calculated. Genomic DNA was analyzed for the rs11212617 SNP. Absolute and relative change of metabolic factors (metformin versus placebo) were compared using Wilcoxon rank and t-tests. Regression models were adjusted for baseline differences and assessed interactions with baseline BMI, insulin, and the SNP. Mean age was 52 years. The majority had T2/3, node positive, hormone receptor positive, HER2 negative BC treated with (neo)adjuvant chemotherapy and hormone therapy. Median baseline body mass index (BMI) was 27.4 kg/m² (metformin) and 27.3 kg/m² (placebo). Median weight change was −1.4 kg (metformin) vs +0.5 kg (placebo). Significant improvements were seen in all metabolic factors, with 6 month standardized ratios (metformin/placebo) of 0.85 (insulin), 0.83 (HOMA), 0.80 (leptin), and 0.84 (hsCRP), with no qualitative interactions with baseline BMI or insulin. Changes did not differ by rs11212617 allele. Metformin (vs placebo) led to significant improvements in weight and metabolic factors; these changes did not differ by rs11212617 allele status.

二甲双胍可能通过间接（由代谢变化介导）或直接机制发挥抗癌作用。目的是检查二甲双胍对非糖尿病受试者代谢因素的影响，并确定这种影响是否因基线 BMI、胰岛素和 CCTG MA.32（一种双盲安慰剂对照随机辅助乳腺癌 (BC)）中的 rs11212617 SNP 而变化。审判。 3649 名 T1-3、N0-3、M0 BC 受试者被随机分配；集中检测治疗前和治疗后 6 个月的空腹血浆中的胰岛素、瘦素、高敏 C 反应蛋白 (hsCRP)。局部测量血糖并计算稳态模型评估（HOMA）。分析基因组 DNA 中的 rs11212617 SNP。使用 Wilcoxon 等级和t检验比较代谢因素（二甲双胍与安慰剂）的绝对和相对变化。回归模型根据基线差异进行调整，并评估与基线 BMI、胰岛素和 SNP 的相互作用。平均年龄为 52 岁。大多数接受（新）辅助化疗和激素治疗的 BC 患者为 T2/3、淋巴结阳性、激素受体阳性、HER2 阴性 BC。中位基线体重指数 (BMI) 为 27.4 kg/m ² （二甲双胍）和 27.3 kg/m ² （安慰剂）。中位体重变化为 -1.4 kg（二甲双胍），而中位体重变化为 +0.5 kg（安慰剂）。所有代谢因素均出现显着改善，6 个月标准化比率（二甲双胍/安慰剂）为 0.85（胰岛素）、0.83（HOMA）、0.80（瘦素）和 0.84（hsCRP），与基线 BMI 或胰岛素没有定性相互作用。 rs11212617 等位基因的变化没有差异。二甲双胍（与安慰剂相比）可显着改善体重和代谢因素；这些变化并不因 rs11212617 等位基因状态而异。