Thiazolidinedione Use Associated With Decreased HCC Risk in Asian Patients With T2D

Asian senior man with glucometer checking blood sugar level in living room at home. Medicine, age, diabetes, health care and old people concept
Investigators conducted a systematic review and meta-analyses to assess the relationship between oral antidiabetic medication classes and the risk of incident hepatocellular carcinoma.

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.

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