Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: A meta-analysis

• Published in: Metabolism, clinical and experimental Vol. 120; p. 154780
• Main Authors: Arvind, Ashwini, Memel, Zoe N., Philpotts, Lisa L., Zheng, Hui, Corey, Kathleen E., Simon, Tracey G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2021
• Subjects: Alpha-glucosidase inhibitors; Carcinoma, hepatocellular; Diabetes mellitus, type 2; Thiazolidinediones; RR; OR; GLP-1; Diabetes mellitus, type 2; aOR; CI; DPP-4; HCC; SGLT-2; Carcinoma, hepatocellular; NOS; Alpha-glucosidase inhibitors; Thiazolidinediones; US
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2021.154780

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. 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). 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%). 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. •Thiazolidinedione use appeared to reduce hepatocellular carcinoma risk in Asians.•Alpha-glucosidase inhibitor use appeared to increase hepatocellular carcinoma risk.•Sulfonylurea use was associated with increased hepatocellular carcinoma risk.•Meglitinide use was not associated with hepatocellular carcinoma incidence.