The beneficial hepatic effects of glucagon-like peptide 1 receptor agonists in patients with diabetes and metabolic dysfunction-associated steatotic liver disease are independent of weight loss

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Despite resmetirom being recently approved for treatingnon-cirrhotic MASH patients in the United States of America (but not elsewhere), weight loss and lifestyle remain the first line and mainstay for treating the condition. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have shown promise in MASLD treatment, as they promote significant weight loss.

Aims

In this study, we assessed the effect of long-term GLP-1 therapy on liver disease severity in a cohort of patients with Type 2 diabetes and MASLD.

Materials and methods

In this retrospective observational study, we included all new MASLD patients seen in the liver clinic (Imperial College Healthcare NHS Trust) from January 2010 to May 2022. Demographic, anthropometric and clinical data were collected at baseline and at the most recent follow-up.

Results

779 patients were included. Among those with Type 2 diabetes mellitus (T2DM) (n = 335), 94 (28%) were prescribed a GLP-1RA for a median period of 38 (1–171.2) months. In those on GLP-1RA, there was a significant improvement in BMI (33.1 vs. 34.9 kg/m², p = 0.005), alanine aminotransferase (ALT) (37 vs. 58 IU/L, p = 0.009), HbA1c (58 vs. 61 mmol/lL, p = 0.006) and CAP score (331 vs. 354 dB/m, p = 0.0001) at the end of follow-up. Finally, among those who were treated with GLP-1RA, 37 patients had <5% weight loss over a median of 38 (10–134) months. In this group, there was also a significant reduction in ALT (32 vs. 58 IU/L, p = 0.0001), AST (30 vs. 36 IU/L, p = 0.004) and CAP score (329 vs. 349 dB/m, p = 0.05) compared with those who lost >5% weight. In this real-life cohort of patients with diabetes and MASLD, treatment with GLP-1RA was associated with greater weight loss and hepatic fat reduction. Of note, a reduction in fat content was observed also in those who did not lose weight.

Conclusion

Treatment with GLP-1RA should be favoured when treating patients with co-existing diabetes and MASLD.