Comparative Effectiveness of Glucagon-like Peptide 1 Agonists Vs Dipeptidyl Peptidase 4 Inhibitors on Liver Outcomes in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Fatty Liver Disease

OBJECTIVES:

Glucagon-like peptide 1 (GLP-1) has been beneficial for liver enzymes in patients with type 2 diabetes (T2DM) and metabolic dysfunction-associated fatty liver disease (MAFLD), but its effectiveness in reducing risk of cirrhosis and hepatocellular carcinoma (HCC) in real-world settings has not been proven. This study aims to evaluate the effectiveness of GLP-1 receptor agonists (GLP-1RA) in improving liver outcomes by comparing them to dipeptidyl peptidase-4 inhibitors (DPP-4i).

METHODS:

The study included adult T2DM and MAFLD patients on metformin, excluding those with substance use disorders, established liver conditions, or liver transplants. Treatments with GLP-1RA or DPP-4i were initiated between January 1, 2014, and December 31, 2020, with a prerequisite of 12-month continuous enrollment. The cohort was identified using the IBM MarketScan database, focusing on time to cirrhosis or HCC diagnosis. Overlap weighting was employed for covariate balance, integrated with a Cox proportional hazards model for survival analysis.

RESULTS:

In a cohort of 38,287 patients, 15,819 were treated with GLP-1RA and 22,468 with DPP-4i. After weighting, the cumulative incidence of composite liver outcomes over seven years was 1.5 in the GLP-1RA group and 2.0% in the DPP-4i group, with an adjusted HR of 0.88 (95% CI, 0.72-1.06). Secondary outcomes showed a lower HCC risk with GLP-1RA, with an adjusted HR of 0.59 (95% CI, 0.34-0.93).

CONCLUSIONS:

GLP-1RA do not significantly reduce cirrhosis risk compared to DPP-4i. However, our study indicates lower risk of HCC in GLP-1RA initiators group. Further studies with longer follow-up periods are needed for conclusive evidence.