In Asian patients with type 2 diabetes, the use of thiazolidinediones was found to be associated with reduced incidence of hepatocellular carcinoma (HCC), while treatment with an alpha-glucosidase inhibitor or sulfonylurea was associated with a slightly increased risk of HCC across a broader patient population, according to study findings published in Metabolism.

Investigators conducted a meta-analysis of clinical trials that reported on oral antidiabetic medication exposure by drug class and HCC incidence. Across 8 observational studies, the researchers reported exposures to sulfonylureas, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and amylin analogs.

The pooled meta-analysis included 281,180 participants with type 2 diabetes. In 6 studies, the mean age ranged between 56 years and 68.8 years.

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In 7 studies (n=280,567), the use of thiazolidinediones was associated with an 8% lower risk of HCC compared with nonuse (adjusted odds ratio [aOR], 0.92; 95% CI, 0.86-0.97; I2=43%), particularly in Asian participants (aOR, 0.90; 95% CI, 0.83-0.97); this was not seen in Western participants (aOR, 0.95; 95% CI, 0.87-1.04).

In 3 studies (n=56,791), the use of alpha-glucosidase inhibitors was associated with an 8% higher risk of HCC compared with nonuse (aOR, 1.08; 95% CI, 1.02-1.14; I2=21%). Sulfonylurea use was associated with an increased risk of HCC in studies that enrolled patients with established underlying liver disease (aOR, 1.06; 95% CI, 1.02-1.11; I2=75%). In 4 studies (n=58,237), there was no association between the use of meglitinides and HCC incidence (aOR, 1.19; 95% CI, 0.89-1.60 I2=72%).

This study was limited by the inclusion of only observational studies, which are prone to bias and confounding, according to the researchers.

Given the findings, the investigators indicate there is a “need for future well-designed prospective clinical studies focused on thiazolidinedione use across various etiologies of chronic liver disease and in different ethnicities,” in addition to prospective research “to determine whether alpha-glucosidase inhibitors and sulfonylureas should be discouraged in patients at high-risk of developing HCC, such as those with advanced liver disease.”

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Arvind A, Memel ZN, Philpotts LL, Zheng H, Corey KE, Simon TC. Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: a meta-analysis. Metabolism. Published online April 20, 2021. doi:10.1016/j.metabol.2021.154780