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Abstract Details
Thiazolidinediones, alpha-glucosidase inhibitors, Meglitinides, sulfonylureas, and hepatocellular carcinoma risk: a meta-analysis
Metabolism. 2021 Apr 20;154780. doi: 10.1016/j.metabol.2021.154780. Online ahead of print.
Ashwini Arvind1, Zoe N Memel2, Lisa L Philpotts3, Hui Zheng4, Kathleen E Corey5, Tracey G Simon6
Author information
1Harvard Medical School, Boston, MA, United States of America; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, United States of America.
2Harvard Medical School, Boston, MA, United States of America; Department of Medicine, Massachusetts General Hospital, Boston, MA, United States of America.
3Treadwell Library, Massachusetts General Hospital, Boston, MA, United States of America.
4Harvard Medical School, Boston, MA, United States of America; Biostatistics Center, Massachusetts General Hospital, Boston, MA, United States of America.
5Harvard Medical School, Boston, MA, United States of America; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, United States of America; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, United States of America.
6Harvard Medical School, Boston, MA, United States of America; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA, United States of America; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, United States of America. Electronic address: tgsimon@mgh.harvard.edu.
Abstract
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, I2 = 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, I2 = 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, I2 = 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, I2 = 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.