GLP-1 Receptor Agonists Show Lower Hazard for Major Adverse Liver Outcomes in MASLD and Type 2 Diabetes
Background
Treatment options for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a prevalent condition often co-occurring with Type 2 Diabetes, are notably limited. While both glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated significant benefits for cardiovascular outcomes in this patient population, their comparative effectiveness on specific liver-related outcomes has remained largely unclear. This study addresses a critical gap by directly comparing these two drug classes for their impact on major adverse liver outcomes (MALO), a key clinical endpoint in MASLD progression.
Study Design
This active comparator, new-user cohort study utilized extensive claims data from Germany spanning 2005-2024, enrolling 45,256 individuals diagnosed with MASLD and Type 2 Diabetes. The cohort comprised new users of GLP-1 RAs (n=9993) and SGLT-2 inhibitors (n=35,263). To ensure comparability, both groups were weighted using matching weights. The primary endpoint was MALO, with secondary outcomes including individual MALO components such as decompensation events, liver transplantation, and hepatocellular carcinoma (HCC), as well as liver cirrhosis and all-cause mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using weighted Cox proportional hazard models over a median 4.3-year follow-up.
Results
Over a median 4.3-year follow-up period, new users of GLP-1 RAs exhibited a lower hazard for MALO compared to SGLT-2 inhibitors, with an HR of 0.91 (95% CI 0.78-1.07). This association was notably stronger when an on-treatment analysis approach was applied, yielding an HR of 0.78 (95% CI 0.58-1.03). Further strengthening these observations, restricting the analysis to hospital diagnoses in the primary position resulted in an HR of 0.77 (95% CI 0.56-1.07) for MALO. Benefits were also observed for several secondary liver-specific outcomes:
The hazard for liver cirrhosis was reduced by 12% (
HR0.88), decompensation events by 9% (HR0.91), and hepatocellular carcinoma (HCC) by 24% (HR0.76). However, no significant difference was found for all-cause mortality, with anHRof 1.04.
Key Findings
- GLP-1 RAs showed a potentially lower hazard for
MALO(HR0.91, 95% CI 0.78-1.07) compared to SGLT-2 inhibitors. - On-treatment analysis revealed a stronger
MALOreduction with GLP-1 RAs (HR0.78, 95% CI 0.58-1.03). - GLP-1 RAs were associated with an 12% lower hazard for liver cirrhosis (
HR0.88). - A 24% lower hazard for hepatocellular carcinoma (
HCC) was observed with GLP-1 RAs (HR0.76). - No significant difference in all-cause mortality was found between the two drug classes (
HR1.04).
Why It Matters
This study provides crucial real-world evidence suggesting that GLP-1 RAs may offer a therapeutic advantage for liver-specific outcomes in patients with MASLD and Type 2 Diabetes when compared to SGLT-2 inhibitors. For clinicians and individuals managing these conditions, this implies that GLP-1 RAs could be a preferred choice when liver protection is a primary concern, potentially influencing prescribing patterns. While both drug classes are beneficial for cardiovascular health, the observed trends for reduced MALO, cirrhosis, and HCC with GLP-1 RAs highlight a distinct liver-centric benefit. This finding encourages further investigation into GLP-1 RAs as a targeted intervention for MASLD progression, potentially leading to new clinical protocols that prioritize these agents for their hepatoprotective effects.
glp-1-ra
sglt-2-inhibitor
masld
type-2-diabetes
liver-cirrhosis
hcc