GLP-1 Receptor Agonists and SGLT2 Inhibitors Reduce Liver-Related Risks and HCC in Type 2 Diabetes: Study
South Korea: A systematic review and meta-analysis published in Hepatology has revealed that GLP-1 receptor agonists and SGLT2 inhibitors are associated with lower risks of liver-related events and hepatocellular carcinoma (HCC) in patients with type 2 diabetes compared with other glucose-lowering therapies. Additionally, GLP-1 receptor agonists were linked to a reduced risk of hepatic decompensation, suggesting a potential protective role in diabetic patients with or at risk for liver disease.
Type 2 diabetes mellitus (T2DM) is increasingly recognized as a modifiable risk factor for chronic liver disease, HCC, and liver-related mortality. While tight glycemic control remains central to diabetes management, the effects of newer antihyperglycemic agents on long-term hepatic outcomes have been less clear.
To address this knowledge gap, researchers led by Ju Hyun Shim from the Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, conducted a comprehensive systematic review and meta-analysis evaluating liver-related outcomes associated with modern diabetes therapies.
The investigators performed an extensive literature search to identify observational cohort studies reporting hepatic complications among patients with T2DM treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 (SGLT-2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors. These outcomes were compared with those seen in patients receiving other glucose-lowering medications. Random-effects models were applied to calculate pooled hazard ratios, and subgroup analyses were conducted in patients with pre-existing chronic liver disease.
The researchers reported the following findings:
- A total of 36 cohort studies were included in the analysis, representing over 5.3 million patients with type 2 diabetes mellitus (T2DM).
- GLP-1 receptor agonists (GLP-1 RAs) were associated with a 23% lower risk of hepatocellular carcinoma (HCC) compared with other glucose-lowering therapies.
- GLP-1 RAs also reduced non-HCC liver-related events by 21%.
- SGLT-2 inhibitors showed similar hepatoprotective effects, with significant reductions in both HCC incidence and overall liver-related complications.
- DPP-4 inhibitors did not confer liver protection; they were not linked to reduced HCC risk and were associated with a higher likelihood of liver-related events compared with other therapies.
- Among patients with chronic liver disease, GLP-1 RAs were the only drug class associated with a significant reduction in hepatic decompensation.
- These findings suggest that GLP-1 RAs may have a protective role in slowing liver disease progression in patients with T2DM and pre-existing liver conditions.
The authors note that while the included studies were observational in nature, the large sample size and consistency of findings across analyses strengthen the reliability of the results. Potential mechanisms underlying the observed benefits may include improvements in insulin resistance, weight reduction, anti-inflammatory effects, and favorable metabolic changes associated with GLP-1 RAs and SGLT-2 inhibitors.
Overall, the large-scale meta-analysis provides compelling evidence that certain newer antidiabetic agents offer liver-related benefits beyond glycemic control. The findings may help inform individualized treatment decisions for patients with T2DM, particularly those at elevated risk for liver complications or HCC.
Reference:
Yang, Jiwon1; Hwang, Yeongseok1; Ju, Jin-Sung2; Han, Seungbong3; An, Jihyun4; Shim, Ju Hyun1. Impact of newer antihyperglycemic agents on hepatic complications: A systematic review and meta-analysis of data from 5.3 million patients with type 2 diabetes mellitus. Hepatology ():10.1097/HEP.0000000000001695, January 29, 2026. | DOI: 10.1097/HEP.0000000000001695
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