Department of Public Health Sciences, School of Public Health, University of Alberta, 2-040 Health Research Innovation Facility, Edmonton, AB, Canada T6G 2E1.
Diabetologia. 2010 Aug;53(8):1631-7. doi: 10.1007/s00125-010-1750-8. Epub 2010 Apr 21.
AIMS/HYPOTHESIS: We explored the relationship between glucose-lowering agents and cancer mortality rates in type 2 diabetes patients, hypothesising a decreased risk of cancer mortality with metformin use and a dose-risk gradient for insulin therapy.
This was a population-based cohort study using administrative data from Saskatchewan Health, Canada. We identified new users of metformin or sulfonylureas from 1 January 1991 to 31 December 1996, with follow-up until death, departure from the province or 31 December 1999. Cox regression analyses were used to estimate the HR of death from cancer, accounting for time-varying exposure to metformin, sulfonylurea, and exogenous insulin therapy.
We identified 10,309 new users of metformin or sulfonylurea. The average follow-up was 5.4 (1.9) years, during which 407 (4.0%) cancer deaths occurred. Adjusting for age, sex and chronic disease score, the adjusted HR for metformin use was 0.80 (95% CI 0.65-0.98) compared with sulfonylurea monotherapy users. Adjusted HRs for subsequent insulin use were 2.22 (0.99-5.00), 3.33 (2.26-4.89) and 6.40 (4.69-8.73) for <3, 3 to 11 and > or = 12 insulin dispensations/year, respectively, compared with patients not on insulin. We observed a similar risk gradient among the sub-cohort of new insulin users.
CONCLUSIONS/INTERPRETATION: Our results support previous reports of a decreased risk of cancer outcomes associated with metformin use relative to sulfonylurea monotherapy. We also provide new evidence of a gradient of cumulative insulin dispensations and cancer mortality rates.
目的/假设：我们探讨了降糖药物与 2 型糖尿病患者癌症死亡率之间的关系，假设使用二甲双胍会降低癌症死亡率风险，而胰岛素治疗则存在剂量-风险梯度。
这是一项基于人群的队列研究，使用了来自加拿大萨斯喀彻温省卫生部门的行政数据。我们从 1991 年 1 月 1 日至 1996 年 12 月 31 日确定了新使用二甲双胍或磺酰脲类药物的患者，随访至死亡、离开该省或 1999 年 12 月 31 日。使用 Cox 回归分析估计癌症死亡的 HR，同时考虑到二甲双胍、磺酰脲类和外源性胰岛素治疗的时间变化暴露情况。
我们确定了 10309 名新使用二甲双胍或磺酰脲类药物的患者。平均随访时间为 5.4（1.9）年，在此期间有 407（4.0%）例癌症死亡。调整年龄、性别和慢性疾病评分后，与磺酰脲类单药治疗相比，二甲双胍治疗的调整 HR 为 0.80（95%CI 0.65-0.98）。随后使用胰岛素的调整 HR 分别为 <3、3 至 11 和 >或= 12 个胰岛素剂量/年时为 2.22（0.99-5.00）、3.33（2.26-4.89）和 6.40（4.69-8.73），与未使用胰岛素的患者相比。在新胰岛素使用者的亚组中，我们观察到了类似的风险梯度。
结论/解释：我们的结果支持了之前关于与磺酰脲类单药治疗相比，使用二甲双胍治疗与癌症结局风险降低相关的报告。我们还提供了新的证据，表明累积胰岛素剂量与癌症死亡率之间存在梯度关系。
