1105-P: The Effect of Canagliflozin on Alanine Aminotransferase (ALT) Levels: Data from the Association of British Clinical Diabetologists (ABCD) Nationwide Audit Programme
Authors: CRABTREE THOMAS S.J. , PHILLIPS SUZANNE M. , EVANS ALISON , SENNIK DEVESH K. , ROHILLA ANURITA , BICKERTON ALEX , DARZY KEN H. , WINOCOUR PETER , CULL MELISSA L. , STRZELECKA ANNA , RAGHAVAN RAJEEV P. , GALLEN IAN W. , YADAGIRI MAHENDER , RYDER ROBERT E. 
Published: June 2020

Background: Nonalcoholic fatty liver disease (NAFLD) is common amongst those with type 2 diabetes (T2DM). Alanine aminotransferase (ALT) is known to correlate with levels of liver inflammation and fibrosis. Recent data from our audit programme showed promising reductions in ALT with dapagliflozin. Our aim was to test the same hypothesis, that canagliflozin may improve ALT levels in patients with T2DM, therefore possibly providing benefit in NAFLD.
Methods: Data were extracted from the ABCD nationwide audit programme and then stratified into 4 groups based on gender and elevated or normal baseline ALT levels using gender specific references ranges (Prati et al). Baseline and follow-up ALT measurements in the 12-month (6-18months) period were required as a minimum. Data were analysed using Stata 16.
Results: 730 datasets were included with mean (±SD) age 61.3yrs (±10.8), 60.1% male, 76% Caucasian (where known), BMI 32.5kg/m2 (±6.5), baseline HbA1c 8.9% (±1.6%) and weight 97.6kg (±22.2) and were broadly similar across all 4 sub-groups. For the entire population, median ALT decreased by 3U/L (95% CI -2, -3; P&lt;0.01). Both male and female subgroups with normal ALT at baseline showed no significant change in ALT. In those with raised ALT at baseline (female ≥19U/L; male ≥30U/L) a change in ALT of -8U/L (95% CI -6, -9U/L; P&lt;0.001) in men and -4U/L in women (95% CI -2, -5; P&lt;0.05). Kruskal-Wallis test confirmed the difference between all groups was significant to P&lt;0.01. No statistically significant correlation was noted between change in weight and change in ALT, which may suggest a weight-loss independent mechanism.
Conclusion: Our data show that ALT decreases with canagliflozin, similar to that demonstrated with dapagliflozin. This decrease is greatest in those with elevated baseline levels. Weight-loss is not a predictor of change in ALT suggesting a potential weight-loss independent mechanism.

Disclosure
T.S.J. Crabtree: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. A. Bickerton: None. K.H. Darzy: None. P. Winocour: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Sanofi. M.L. Cull: None. A. Strzelecka: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. I.W. Gallen: None. M. Yadagiri: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S.