噻唑烷二酮类、α-葡萄糖苷酶抑制剂、米格列奈、磺酰脲类药物和肝细胞癌风险：一项荟萃分析。
Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: A meta-analysis.
机构信息
Harvard Medical School, Boston, MA, United States of America; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, United States of America.
Harvard Medical School, Boston, MA, United States of America; Department of Medicine, Massachusetts General Hospital, Boston, MA, United States of America.
出版信息
Metabolism. 2021 Jul;120:154780. doi: 10.1016/j.metabol.2021.154780. Epub 2021 Apr 21.
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Effects of second-line oral antidiabetic medications on incident HCC risk in individuals with type 2 diabetes mellitus remain unclear. This study evaluated associations between sulfonylureas, thiazolidinediones, meglitinides and alpha-glucosidase inhibitors, and incident HCC risk.
METHODS
We systematically reviewed all studies on PubMed, Embase and Web of Science databases. Studies were included if they documented: (1) exposure to oral antidiabetic medication classes; (2) HCC incidence; (3) relative risks/odds ratios (OR) for HCC incidence. Eight eligible observational studies were identified. We performed random-effects meta-analyses to calculate pooled adjusted ORs (aORs) and 95% confidence intervals (CI).
RESULTS
Thiazolidinedione use (7 studies, 280,567 participants, 19,242 HCC cases) was associated with reduced HCC risk (aOR = 0.92, 95% CI = 0.86-0.97, I = 43%), including among Asian subjects (aOR = 0.90, 95% CI = 0.83-0.97), but not Western subjects (aOR = 0.95, 95% CI = 0.87-1.04). Alpha-glucosidase inhibitor use (3 studies, 56,791 participants, 11,069 HCC cases) was associated with increased HCC incidence (aOR = 1.08; 95% CI = 1.02-1.14, I = 21%). Sulfonylurea use (8 studies, 281,180 participants, 19,466 HCC cases) was associated with increased HCC risk in studies including patients with established liver disease (aOR = 1.06, 95% CI = 1.02-1.11, I = 75%). Meglitinide use (4 studies, 58,237 participants, 11,310 HCC cases) was not associated with HCC incidence (aOR = 1.19; 95% CI = 0.89-1.60, I = 72%).
CONCLUSIONS
Thiazolidinedione use was associated with reduced HCC incidence in Asian individuals with diabetes. Alpha-glucosidase inhibitor or sulfonylurea use was associated with modestly increased HCC risk; future research should determine whether those agents should be avoided in patients with chronic liver disease.
背景与目的
肝细胞癌（HCC）仍然是全球癌症相关死亡的主要原因。2 型糖尿病患者二线口服抗糖尿病药物对 HCC 发病风险的影响仍不清楚。本研究评估了磺酰脲类、噻唑烷二酮类、格列奈类和α-葡萄糖苷酶抑制剂与 HCC 发病风险之间的关联。
方法
我们系统地检索了 PubMed、Embase 和 Web of Science 数据库中的所有研究。如果研究记录了以下内容，则将其纳入：（1）暴露于口服抗糖尿病药物类别；（2）HCC 发病率；（3）HCC 发病率的相对风险/优势比（OR）。确定了 8 项符合条件的观察性研究。我们进行了随机效应荟萃分析，以计算汇总调整后的 OR（aOR）和 95%置信区间（CI）。
结果
噻唑烷二酮类药物的使用（7 项研究，280567 名参与者，19242 例 HCC 病例）与 HCC 风险降低相关（aOR=0.92，95%CI=0.86-0.97，I=43%），包括亚洲受试者（aOR=0.90，95%CI=0.83-0.97），但不包括西方受试者（aOR=0.95，95%CI=0.87-1.04）。α-葡萄糖苷酶抑制剂的使用（3 项研究，56791 名参与者，11069 例 HCC 病例）与 HCC 发生率增加相关（aOR=1.08；95%CI=1.02-1.14，I=21%）。磺酰脲类药物的使用（8 项研究，281180 名参与者，19466 例 HCC 病例）与包括患有已确诊肝病的患者的研究中的 HCC 风险增加相关（aOR=1.06，95%CI=1.02-1.11，I=75%）。格列奈类药物的使用（4 项研究，58237 名参与者，11310 例 HCC 病例）与 HCC 发生率无关（aOR=1.19；95%CI=0.89-1.60，I=72%）。
结论
噻唑烷二酮类药物的使用与亚洲糖尿病患者 HCC 发病率降低有关。α-葡萄糖苷酶抑制剂或磺酰脲类药物的使用与 HCC 风险适度增加相关；未来的研究应确定这些药物是否应避免用于慢性肝病患者。
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