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过氧化物酶体增殖物激活受体γ激动剂吡格列酮与2型糖尿病患者的恶性肿瘤风险

PPAR-γ agonist pioglitazone and the risks of malignancy among type2 diabetes mellitus patients.

作者信息

See Lai-Chu, Wu Chao-Yi, Tsai Chung-Ying, Lee Cheng-Chia, Chen Jia-Jin, Jenq Chang-Chyi, Chen Chao-Yu, Chen Yung-Chang, Yen Chieh-Li, Yang Huang-Yu

机构信息

Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.

出版信息

Acta Diabetol. 2025 Apr;62(4):531-542. doi: 10.1007/s00592-024-02378-y. Epub 2024 Sep 30.

Abstract

AIMS

PPAR-gamma shows promise in inhibiting malignancy cell progression. However, pioglitazone, the sole current PPAR-gamma agonist, was reported to have risks of bladder cancer in previous clinical researches. This study is aimed to assess the influence of pioglitazone on the development of tumors.

METHODS

By using Taiwan's National Health Insurance Research Database, this nested case-control study identified incident type2 diabetes initiating metformin treatment between 2000 and 2014, and then categorized into two groups based on whether they developed malignancies after enrollment or not. The index date was defined as the date of malignancy diagnosis in the cancer group or a matched date in the non-cancer group. We analyzed the exposure to pioglitazone preceding the index date.

RESULTS

47,931 patients in the cancer group and 47,931 patients in the matched non-cancer group were included. The non-cancer group exhibited a significantly higher rate of pioglitazone prescription before the index date for overall malignancies (odds ratios for pioglitazone use were 0.91, 0.92, 0.94, and 0.93 in the first, second, third, and fourth years before the index date). For breast cancer and prostate cancer, pioglitazone was frequently prescribed in the non-cancer group, whereas for pancreatic cancer, pioglitazone use was more common in the cancer group.

CONCLUSIONS

PPAR-gamma agonists may be associated with reduced risks of overall malignancies, particularly for breast and prostate cancers. However, it may be linked to an elevated risk of pancreatic cancer.

摘要

目的

过氧化物酶体增殖物激活受体γ(PPAR-γ)在抑制恶性肿瘤细胞进展方面显示出前景。然而,目前唯一的PPAR-γ激动剂吡格列酮在以往的临床研究中被报道有膀胱癌风险。本研究旨在评估吡格列酮对肿瘤发生发展的影响。

方法

通过使用台湾国民健康保险研究数据库,这项巢式病例对照研究确定了2000年至2014年间开始使用二甲双胍治疗的新发2型糖尿病患者,然后根据入组后是否发生恶性肿瘤分为两组。索引日期定义为癌症组的恶性肿瘤诊断日期或非癌症组的匹配日期。我们分析了索引日期之前吡格列酮的暴露情况。

结果

纳入癌症组47931例患者和匹配的非癌症组47931例患者。非癌症组在索引日期前总体恶性肿瘤的吡格列酮处方率显著更高(索引日期前第一、第二、第三和第四年使用吡格列酮的比值比分别为0.91、0.92、0.94和0.93)。对于乳腺癌和前列腺癌,非癌症组经常开具吡格列酮处方,而对于胰腺癌,癌症组使用吡格列酮更为常见。

结论

PPAR-γ激动剂可能与总体恶性肿瘤风险降低有关,尤其是乳腺癌和前列腺癌。然而,它可能与胰腺癌风险升高有关。

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