The effect of dapagliflozin on alanine aminotransferase as a marker of liver inflammation: updated results from the ABCD dapagliflozin audit

Thomas SJ Crabtree, Mahender Yadagiri, Ian Gallen, Suzanne Phillips, Alison Evans, Anurita Rohilla, Devesh Sennik, Alex Bickerton, Susannah Rowles, Iskandar Idris, Robert E J Ryder, On behalf of the ABCD dapagliflozin audit contributors

Abstract


Introduction: People with type 2 diabetes are known to be at increased risk of non-alcoholic fatty liver disease (NAFLD). There is increasing evidence of diabetes treatments with benefits of also improving NAFLD. Although mostly focused on glucagon-like peptide 1 agonists, sodium-glucose linked transporter 2 inhibitors may also have some promise in improving markers of NAFLD.

Method: Data were extracted from the ABCD nationwide dapagliflozin audit tool. Alanine aminotransferase (ALT) was available in these data and was used as a marker of liver inflammation. Patients were stratified based on baseline ALT levels to see if this predicted response to treatment.

Results: 1,873 patients were included for analysis (mean±SD age 58.7±10 years, 60.8% male, median duration of diabetes 3.5 years (IQR 1.5–9)) and were followed up in this study for an average of 11.4 months. Where known (n=280), 60.8% of these were Caucasian. Baseline HbA1c was 78±17.2 mmol/mol, weight 102.1±22.5 kg and body mass index (BMI) 34.2±7.6 kg/m2. Median ALT reduction overall was 4 U/L (95% CI 3 to 4; p<0.001). Reductions in weight (3.2 kg; 95% CI 2.9 to 3.5), BMI (0.9 kg/m2, 95% CI 0.6 to 1.2) and HbA1c (10.8 mmol/mol, 95% CI 10.1 to 11.5) (0.9%, 95% CI 0.8% to 1.0%) were all significant (p<0.001). Where ALT was elevated at baseline (>19 U/L female; >30 U/L male), the median reduction in ALT was 5 U/L in women (95% CI 4 to 6; p<0.0001) and 10 U/L in men (95% CI 8 to 11; p<0.0001). Stratified into three groups by ALT using the male reference range and twice this, there were reductions in ALT in all groups, which was greatest (24 U/L 95% CI 20 to 27) in the subgroup with baseline ALT >59 U/L.

Conclusion: Our observational data suggest significant reductions in ALT as a possible marker of liver inflammation in those taking dapagliflozin. This appears to be greatest in those with the most elevated levels at baseline.


Keywords


dapagliflozin, real-world, alanine aminotransferase (ALT), non-alcoholic fatty liver disease, SGLT-2

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References


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DOI: https://doi.org/10.15277/bjd.2020.239

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