甘精胰岛素不增加癌症风险

芝加哥——美国糖尿病学会(ADA)年会上公布的前瞻性随机ORIGIN试验的分支研究结果显示，在心血管风险高的糖尿病前期或2型糖尿病患者中，常规应用甘精胰岛素并不会增加癌症(包括胰腺癌)风险。


Louise Bordeleau博士

甘精胰岛素(Lantus)组和标准治疗组未校正的任何癌症发生率均为1.32/100人-年，癌症死亡率相似，分别为0.51/100人-年和0.54/100人-年。研究者Louise Bordeleau博士表示，每日应用甘精胰岛素持续6.2年(中位数)对癌症事件——包括任何癌症、新发或复发癌症、癌症相关死亡及各种亚型癌症——的影响是中性的。

在该分析中，82%的患者有糖尿病病史，35%为女性，甘精胰岛素组1年和6年时的中位胰岛素剂量分别为0.31 U/kg和0.40 U/kg。患者的平均年龄为63.5岁。共953例(7.6%)患者发生癌症。新诊断糖尿病的患者发生癌症的比例较高(8.5% vs. 5.9%；P = 0.0001)。虽然二甲双胍暴露和剂量在研究期间均增加，但这两者对任何癌症事件或特异性癌症的风险均无影响。发生和未发生癌症的患者应用二甲双胍的比例分别为27.6%和27.4%，差异不显著。

与未发生癌症的患者相比，发生癌症的患者的年龄明显更大(平均66.1岁 vs. 63.3岁)，当前吸烟(15% vs. 12%)或既往吸烟(54% vs. 46%)的比例明显更高；每周饮酒≥2次(30.2% vs. 22.1%)和既往曾发生心血管事件(64.3% vs. 58.4%)的比例也更高。

探索性分析显示，随机分组后的糖化血红蛋白A1c、降糖治疗和体重对癌症风险无影响。

ORIGIN由赛诺菲公司资助。Bordeleau博士声明无经济利益冲突。

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By: PATRICE WENDLING, Oncology Practice

CHICAGO – Regular insulin glargine use does not increase the risk of cancer, including pancreatic cancer, in patients with prediabetes or type 2 diabetes and high cardiovascular risk, according to a substudy of the prospective randomized ORIGIN trial.

The unadjusted rate of any cancer was 1.32 per 100 person-years in patients receiving insulin glargine (Lantus) or standard care. Cancer death rates per 100 person-years were similar, at 0.51 and 0.54, respectively.

"Daily exposure to glargine for a median of 6.2 years had a neutral effect on cancer events, including any cancers, new or recurrent cancers, cancer-related mortality, and various subtypes of cancer," Dr. Louise Bordeleau said at the annual scientific sessions of the American Diabetes Association.
 
Previous results from the pivotal ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial, a double-blind, randomized trial with a 2-by-2 factorial design, showed no effect of insulin glargine on the primary endpoints of heart attack or stroke among the 12,537 patients (N. Engl. J. Med. 2012;367:319-28).

The new data are reassuring, particularly the absence of any spike in pancreatic cancer, session cochair Dr. Bessie Young, with the University of Washington in Seattle, said in an interview. Retrospective analyses of claims databases have linked insulin use to incidence cancers and metformin to reduced cancer risk. The ADA also recently called for an independent review of clinical data on incretin therapies used to lower glucose levels, because of safety concerns the drugs may increase the risk of pancreatic cancer and pancreatitis in type 2 diabetes.

In the current analysis, 82% patients had a prior diagnosis of diabetes, 35% were women, and the median insulin dose in those allocated to glargine insulin was 0.31 U/kg at 1 year and 0.40 U/kg at 6 years. Their mean age was 63.5 years.

In all, 953 patients (7.6%) were diagnosed with cancer, said Dr. Bordeleau, of the department of oncology at McMaster University, Hamilton, Ont.

Patients with new diabetes were more likely to develop cancer (8.5% vs. 5.9%; P = .0001). Metformin exposure and dose did not impact the risk of any cancer events or specific cancers, although both exposure and dose increased over the study period, she said. Metformin use was reported in 27.6% of those with cancer and 27.4% without, a nonsignificant difference.

Patients who experienced cancer versus those who did not were significantly more likely to be older (mean age, 66.1 vs. 63.3 years), current smokers (15% vs. 12%), or ex-smokers (54% vs. 46%); and were more likely to drink alcohol more than twice a week (30.2% vs. 22.1%) and have a prior cardiovascular event (64.3% vs. 58.4%).

In exploratory analyses, postrandomization hemoglobin A1c, glucose-lowering therapies, and weight had no effect on cancer risk, Dr. Bordeleau said.

ORIGIN was funded by Sanofi. Dr. Bordeleau reported having no financial disclosures.