Recent research published in the Journal of Gut by Wester et.al highlights the potential of glucagon-like peptide-1 receptor (GLP1) agonists to reduce the risk of developing cirrhosis and liver cancer in individuals with chronic liver disease.
Chronic liver diseases pose a significant health challenge, often leading to decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality. In particular, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with type 2 diabetes, serving as a major predictor for its presence and severity. Additionally, type 2 diabetes is a significant risk factor for the progression of various liver diseases, potentially due to the interplay between hepatic steatosis, steatohepatitis, and other liver conditions. At present, MASLD lacks approved pharmacotherapy options. GLP1 agonists, approved for treating type 2 diabetes and obesity to manage weight and blood glucose, have shown potential in resolving metabolic dysfunction-associated steatohepatitis (MASH) in non-cirrhotic MASLD patients during phase II trials. However, their impact on fibrosis regression is yet to be conclusively determined, with large phase III trials still several years away from completion.
Phase II trials have demonstrated the effective treatment of MASH by GLP1 agonists, though their impact on fibrosis regression may be limited. Researchers aimed to investigate the long-term causal effects of GLP1 agonists on major adverse liver outcomes (MALO) in patients with any type of chronic liver disease and type 2 diabetes. Wester and colleagues employed an inverse probability-weighted marginal structural model to assess parametric estimates of the 10-year MALO risk in initiators of GLP1 agonists compared to non-initiators, randomly sampling 5% of the non-initiators to enhance computational efficiency. According to the study, individuals who initiated treatment with GLP1 agonists had a 10-year risk of major adverse liver outcomes (MALO) at 13.3% (42 out of 1026) compared to non-initiators, whose risk was 14.6% (1079 out of 15,633) in the intention-to-treat analysis. The results of the study indicated that prolonged use of these medications considerably reduced the risk of developing severe liver conditions such as cirrhosis and liver cancer.
The prevalence of fatty liver disease is high, with approximately 1 in 5 individuals being affected and 1 in 20 individuals progressing to severe liver disease. The promising findings of the present study suggest that GLP1 agonists could be a potential avenue for lowering the risk of chronic liver disease progression in individuals with concurrent type 2 diabetes, provided the therapy is consistently adhered to over time. Notably, participants who maintained the medication for over a decade demonstrated a remarkable 50% reduction in the likelihood of developing severe liver disease. While these results are encouraging, the necessity for further validation through randomized trials is evident.
Reference
Wester A, Shang Y, Toresson Grip E, Matthews AA, Hagström H. Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes. Gut. 2024 Jan 22;gutjnl-2023-330962.