Obesity and type 2 diabetes are important drivers for the development of nonalcoholic fatty liver disease (NAFLD) . Glucagon-like peptide-1 receptor agonists (GLP1RAs) are efficacious for these conditions, but their potential as treatments for NAFLD remains unclear. As serum ALT concentration is routinely measured in clinical care, we evaluated the impact of the GLP1RA, semaglutide, on ALT in those at risk of NAFLD.

Methods: Data submitted to the ABCD semaglutide audit (launched in 2019) were analysed. Change in ALT from baseline was assessed and corrected for change in covariates and concomitant medications using a multiple linear regression in Stata 16 . Baseline ALT levels were used to perform a stratified analysis as follows: normal (ALT 0-29U/L) , mildly elevated (30-59 U/L) and significantly elevated (≥60U/L) . Missing data were multiply imputed.

Results: Data for 1,623 individuals (50.2% men) were included with baseline (mean±SD) : age 58.9±11.0 years, HbA1c9.4±1.7%, weight 104.6±2.8kg, BMI 37.1±7.4kg/m2 and median (IQR) diabetes duration 10.9 years (6-15.4) and ALT 26U/L (19-36) . Median (IQR) follow-up was 8.2 months (5-12) . At follow-up, changes in HbA1c and weight were -1.2% (95%CI -1.0, -1.3; p<0.001) and -2.4kg (95%CI -1.7, -3.1; p<0.001) respectively. No significant change in ALT was seen across the entire cohort (p=0.172) . However, ALT rose in the normal group (+14.6U/L; 95%CI 10.4, 18.8; p<0.001) and fell in the significantly elevated group (-16.2U/L; 95%CI -11.8, -20.5; p<0.001) . No change was noted in the mildly elevated group (p=0.33) . The differences between groups were statistically significant (p<0.0001) .

Conclusion: Among patients with significantly raised ALT, semaglutide was associated with ALT reduction, but this finding may result from regression to the mean. Measurement in parallel of further biomarkers of liver fibrosis will be required to assess the potential of semaglutide as a NAFLD therapy.


T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. D.K. Sennik: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi. D. Barnes: None. S. Sivappriyan: None. K. Adamson: None. S.M. Phillips: None. A. Evans: None. N. Larsen: None. A. Panesar: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None.


The ABCD audit is support by an unrestricted grant from NovoNordisk

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