Metformin use lowers hepatocellular cancer risk in NAFLD patients with diabetes: Study
USA: The use of metformin may lower the risk of hepatocellular cancer (HCC) in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), claims a recent study. The use of combination therapy, however, was associated with increased risk.
The findings, published in the journal Hepatology, suggest that glycemic control can serve as a biomarker for risk stratification of HCC in patients with diabetes and NAFLD.
In patients with nonalcoholic fatty liver disease, those with type 2 diabetes are at an increased risk of progression to HCC. However, there is no clarity on the determinants of HCC risk in these patients. To get some clarity on the topic, Jennifer R. Kramer, Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA, and colleagues aimed to analyze the risk of hepatocellular cancer in patients with NAFLD and type 2 diabetes mellitus (DM) in a retrospective cohort study.
For this purpose, the researchers included a cohort of patients with DM and NAFLD diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008. Patients were followed from the date of NAFLD diagnosis to HCC, death, or 12/31/2018.
Landmark Cox proportional hazards models were used to determining the effects of anti-DM medications (insulin, metformin, sulfonylureas) and glycemic control (percent of follow-up time with hemoglobin A1c < 7%) on HCC risk after adjusting for demographics and other metabolic traits (hypertension, obesity, dyslipidemia).
Based on the study, the researchers reported the following findings:
- A total of 85,963 patients with NAFLD and DM were identified. In total, 524 patients developed HCC during a mean of 10.3 years of follow-up.
- Most common treatments were metformin monotherapy (19.7%), metformin-sulfonylureas (19.6%), insulin (9.3%), and sulfonylureas monotherapy (13.6%).
- Compared with no medication, metformin was associated with 20% lower risk of HCC.
- Insulin had no effect on HCC risk.
- Insulin in combination with other oral medications was associated with a 1.6 to 1.7-fold higher risk of HCC.
- Adequate glycemic control was associated with a 31% lower risk of HCC.
The researchers conclude, "metformin use in a large cohort of patients with NAFLD and DM was associated with reduced risk of HCC, the use of combination therapy however was associated with increased risk."
"Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes," they wrote.
Reference:
Kramer JR, Natarajan Y, Dai J, Yu X, Li L, El-Serag HB, Kanwal F. Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease. Hepatology. 2022 Jun;75(6):1420-1428. doi: 10.1002/hep.32244. Epub 2021 Dec 19. PMID: 34779535; PMCID: PMC9107529.
