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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<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<0.001) in men and -4U/L in women (95% CI -2, -5; P<0.05). Kruskal-Wallis test confirmed the difference between all groups was significant to P<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. [ABSTRACT FROM AUTHOR]

In the ABCD nationwide liraglutide audit the impact of liraglutide on HbA1c was found to lessen with increasing duration of diabetes (abstract 1038-P, ADA 2012). We were interested to examine the relationship between change in HbA1c and duration of diabetes in response to canagliflozin in real clinical use in the ABCD nationwide canagliflozin audit. By December 2018 the audit had accumulated data on 972 canagliflozin treated patients of whom there were 604 with baseline HbA1c ≥ 7% and follow-up HbA1c (mean ± SD age 60.3 ± 11.1 year, BMI 33.7 ± 6.7 kg/m2, 62% male, median (IQR) diabetes duration 6.0 (2.6-11) year). By 1st return to clinic after commencing canagliflozin at median (IQR) 4.1 (3.0-6.1) months, mean ± SD HbA1c fell by 0.91 ± 1.2%, from 9.2 ± 1.5 to 8.3 ± 1.3% (p<0.001). Patients with duration of diabetes data (n=434) were divided into 3 groups: 0-5, 6-10, >10 years with mean ± SD baseline HbA1c 9.1 ± 1.6, 9.2 ± 1.5 and 9.3 ± 1.3% respectively (p=0.62). The mean ± SD falls in HbA1c for the 3 groups were 0.87 ± 1.3%, 0.88 ± 1.2%, and 0.86 ± 1.2%, respectfully (p=0.99) (Figure). There was thus no relationship between duration of diabetes and fall in HbA1c in this audit of canagliflozin in real clinical use in the UK. This result contrasts with that from the ABCD liraglutide audit and is in keeping with the differing modes of action of liraglutide and canagliflozin. Disclosure: R.E.J. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. A. Bickerton: Employee; Self; MyWay Digital Health. K. Thong: None. M. Yadagiri: None. M.L. Cull: None. M.C. Wyres: None. P. Winocour: None. K.H. Darzy: None. A. Strzelecka: None. S.G. Gohil: None. A. Gallagher: Speaker's Bureau; Self; Novo Nordisk A/S. I.W. Gallen: None. Funding: Association of British Clinical Diabetologists [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) commonly co-exists with type 2 diabetes. Alanine aminotransferase (ALT) levels are known to correlate, to some degree, with liver inflammation. Methods: All data submitted to the ABCD nationwide empagliflozin audit programme were included if they had relevant baseline and follow-up data and were then stratified by baseline ALT for two analyses: 1) using gender-specific reference ranges; 2) by normal (<30U/L), mildly raised (30-59 U/L) and very raised levels (twice male reference limit, ≥60 U/L). Data were analysed using non-parametric methods due to skew using Stata SE 16. Results: 6510 datasets were included with mean(±SD) age 60.0yrs(±10.4), 61.2% male, BMI 34.2kg/m2(±6.5), HbA1c 9.3%(±1.6) and weight 98.4kg(±21.23). For the entire population, median ALT changed by -4 U/L (95% CI -4, -4; P<0.01). When stratified, in both analyses, all groups showed significant changes in ALT from baseline. These are shown in Figure 1. Conclusion: Our data demonstrate changes in ALT associated with empagliflozin use. Decreases of a significantly greater magnitude are noted in those with raised ALT at baseline. Empaglifozin may provide benefit in NAFLD. Disclosure: T. S. J. Crabtree: Other Relationship; Self; Novo Nordisk, Sanofi. J. Elliott: Advisory Panel; Self; Abbott, Speaker's Bureau; Self; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. A. Bickerton: None. I. W. Gallen: None. K. Dhatariya: Speaker's Bureau; Self; Novo Nordisk. M. L. Cull: None. A. Evans: None. S. M. Phillips: None. R. E. Ryder: Other Relationship; Self; Novo Nordisk. Funding: Boehringer Ingelheim [ABSTRACT FROM AUTHOR]

Background: Data previously presented from our audit programme showed that sodium-glucose co-transporter 2 inhibitors (SGLT2s) remain equally effective at reducing HbA1c irrespective of duration of diabetes. This analysis was performed to establish if the same held true for empagliflozin. Methods: Data extracted from the ABCD nationwide empagliflozin audit was stratified into groups based on duration of diabetes: group 1 (<5yrs; n=2320), group 2 (≥5yrs, <10yrs; n=1516), group 3 (≥10yrs; n=2224). Data was analysed using paired t-tests and ANOVA in Stata 16. Results: 6060 datasets were included with mean (±SD) age 59.5yrs (±10.4), 61.1% male, 86% Caucasian (where known), BMI 33.2kg/m2 (±7.2), baseline HbA1c 9.2% (±1.6%) and weight 98.1kg (±21.0). These were broadly similar across all 3 sub-groups apart from age, which understandably increased with duration of diabetes (group 1 57.7yrs±10.8 v group 3 62.0yrs±9.7). Decreases in HbA1c (%) from baseline were observed in all groups, greatest in group 1 (-1.27%; 95% CI -1.19%, -1.35%) and least pronounced in group 3 (-0.9%; 95% CI -0.83%, -0.97%). ANOVA showed significant differences amongst the groups for HbA1c change (P<0.001) but not for weight, BMI or blood pressure. Further analysis has demonstrated no significant difference between HbA1c reductions in group 1 and 2 (P=0.79) but very significant differences (P<0.001) between both groups 1 and 2 and group 3, suggesting the change in response occurs at around the 10 year mark. Conclusions: This analysis demonstrates statistically significant differences in the magnitude of HbA1c change (due to empagliflozin use) in those with shorter v longer durations of diabetes, appearing to occur after 10 years. Although the pattern is generally comparable to other SGLT2s the statistical significance is likely to have been increased from previous data due to a larger sample. The clinical significance of such minor differences in effect is not clear. Disclosure: T.S.J. Crabtree: None. K. Adamson: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. A.M. Robinson: None. M. Atkin: Speaker's Bureau; Self; AstraZeneca, Napp Pharmaceuticals. D.S. Morris: None. D.M. Williams: None. J.W. Stephens: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Napp Pharmaceuticals, Novo Nordisk A/S. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. M.L. Cull: 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. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Introduction: Alanine transaminase (ALT) is an important marker for Nonalcoholic Fatty Liver Disease (NAFLD), and its levels are reduced following treatment with SGLT2i. However, how raised ALT levels and hence NAFLD affects HbA1c response to SGLT2i is not known. Methods: Data for this study was obtained from the ABCD nationwide audits of patients with type 2 diabetes started on SGLT2i. We used a gradient boosting machine learning algorithm (GBM) to identify if ALT is an important predictor of glycaemic response to SGLT2i. The results of the GBM model were confirmed using linear regression analysis where the absolute drop in HbA1c was modelled as a dependent variable with baseline ALT as independent variable adjusted for relevant covariates. Results: We studied 9,609 patients initiated on Empagliflozin (n=5061), Dapagliflozin (n=3711) or Canagliflozin (n=837). The mean age of the study population was 59(±10.3), 62% male with a mean weight of 96.6(±18.8), baseline eGFR 81(±11) and baseline HbA1c 9.06% (±1.62). At a median 5.8 months follow-up, the mean HbA1c drop was 0.81% and was similar in all three types of SGLT2i. The drop in HbA1c was 0.62%, 0.78% and 1.01% in 1st 2nd and 3rd quartiles of baseline ALT, respectively (P-Anova <0.0001). In the GBM analysis the important predictors of glycaemic response were baseline weight (relative influence (RI)=71%), and baseline HbA1c (RI= 7.2%), baseline ALT (RI= 5.6%) baseline creatinine (RI= 4.9%). The model accuracy was 0.73 (0.71-0.75) and area under the curve was 0.83. In the linear regression model, higher baseline ALT was associated with a larger drop in HbA1c (beta=0.007, P<0.0001) after adjustments for baseline weight, weight loss, baseline HbA1c, and duration of diabetes. Conclusion: Higher baseline ALT levels are associated with a more significant SGLT2 induced HbA1c drop and SGLT2 inhibitors and are likely to be more effective in those with NAFLD. Disclosure: H. Deshmukh: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. 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. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. K. Adamson: None. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose linked transporter 2 inhibitors (SGLT2s) are currently favoured for their tolerability, cardiovascular benefit and renal protective effects. However, due to their mechanism of action, they are only licensed for use in those with preserved renal function at baseline. Previous analyses with other drugs in the class showed potential benefits even when used in those with estimated glomerular filtration rate (eGFR) below licensed level. Methods: Data was extracted from the ABCD nationwide empagliflozin audit and then stratified into groups, as follows, based on baseline eGFR (mL/min/1.73m2): CKD1 (n=2900, eGFR≥90), CKD2 (n=2753, eGFR<90, eGFR≥60), CKD3a (n=210, eGFR<60, eGFR≥45) and CKD3b+ (n=17, eGFR<45). Data was analysed using paired t-tests and ANOVA in Stata 16. Results: 5880 datasets were included with mean (±SD) age 59.5yrs (±10.4), 61.1% male, 86% Caucasian (where known), BMI 33.1kg/m2 (±6.6), HbA1c 9.17% (±1.61) and median duration diabetes 7.3 years (2.2-12.1 IQR) and were broadly similar across groups apart from age: those with more impaired renal function being generally older (CKD1 55.4yrs±9.5 v CKD3b+ 69.6yrs±8.5) with a longer duration diabetes with median (IQR) in CKD1 6.6yrs (1.8-10.9) v CKD3b+ 14.5yrs (8.9-17.3). Reductions in HbA1c, weight and BMI occurred in all groups (P<0.005); reductions in HbA1c were of a smaller magnitude as eGFR declined (ANOVA P<0.01). Changes in systolic (SBP) and diastolic blood pressure (DBP) were significant in those in CKD1- CKD3a but not in CKD3b+ (SBP +2.6mmHg, 95% CI +14.9, -9.6). eGFR was observed to decrease in CKD1 and CKD2 (CKD1 eGFR -2.1mL/min/1.73m2, CI 95% -1.8, -2.3). Conclusion: The use of empagliflozin at eGFR<45mL/min/1.73m2 may still confer HbA1c improvement (although perhaps of lower magnitude) and weight loss, though SBP and DBP reduction may be limited. More evidence is needed regarding its use at lower levels of eGFR. Disclosure: T.S.J. Crabtree: None. K. Adamson: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. A.M. Robinson: None. M. Atkin: Speaker's Bureau; Self; AstraZeneca, Napp Pharmaceuticals. D.S. Morris: None. D.M. Williams: None. J.W. Stephens: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Napp Pharmaceuticals, Novo Nordisk A/S. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. M.L. Cull: 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. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Introduction: We investigated characteristics and treatment outcomes of patients treated with empagliflozin in a large-scale audit of routine clinical practice in the UK. Methods: Data was obtained from the Association of British Clinical Diabetologists Nationwide Empagliflozin Audit. Between December 2014 to September 2018, multiple sites submitted data through 10 major centers on 1947 patients with at least one follow-up visit after empagliflozin initiation. Results: Baseline characteristics of patients were, mean±SD, age 59.9±9.9 years, diabetes duration 6.4±5.4 years, HbA1c 9.41±1.43%, weight 99.6±20.8 years, BMI 33.6±9.1 kg/m2and 62.1% were male. Proportion of use of empagliflozin 25mg (vs. 10mg), GLP-1 receptor agonist, and insulin were 63.7%, 13.7% and 20.1%, respectively. There were 44.9%, 49.9%, 5.1% and 0.1% of patients with eGFR>90, 60-89, 45-59 and <45 ml/min/1.73m2, respectively. By 26 weeks, treatment with empagliflozin was associated with, mean±SD, HbA1c reduction of 1.35±1.49% (p<0.0001), weight reduction of 3.6±5.1 kg (p<0.0001) and systolic blood pressure reduction of 5±14 mmHg (p<0.0001). Conclusions: An audit of empagliflozin use in the UK revealed poorly controlled diabetes being frequently encountered in practice in contrast to randomized clinical trials. There was a preponderance of empagliflozin 25mg dose use, disproportionate prescribing to men rather than women, and frequent co-prescription with GLP-1 receptor agonists and insulin. The audit showed excellent adherence to prescribing guidelines in relation to avoiding empagliflozin use in patients with eGFR<45 ml/min/1.73m2. There was similar treatment efficacy with empaglilfozin as was seen in clinical trials. Disclosure: K. Thong: None. J. Chung-Wah-Cheong: None. M. Yadagiri: None. M.L. Cull: None. A. Bickerton: Employee; Self; MyWay Digital Health. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. H. Reid: None. D.S. Morris: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NAPP Pharmaceuticals Limited, Novo Nordisk A/S, Sanofi-Aventis. M. Atkin: Advisory Panel; Self; NAPP Pharmaceuticals Limited. Consultant; Self; My mHealth. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. A.M. Robinson: Advisory Panel; Self; Takeda UK. D.M. Williams: None. J.W. Stephens: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, NAPP Pharmaceuticals Limited. K. Adamson: None. I.W. Gallen: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. Funding: Association of British Clinical Diabetologists [ABSTRACT FROM AUTHOR]

Introduction: We investigated clinical parameters that are potentially associated with improved empagliflozin treatment response. Methods: We obtained data from a large-scale audit of empagliflozin use in the UK. We analyzed the association between patients' baseline age, HbA1c, weight, diabetes duration, alanine aminotransferase (ALT), sex, chronic kidney disease (CKD) stage, empagliflozin dose (25 vs. 10mg), use of GLP-1RAs and use of insulin with HbA1c and weight changes at 26 weeks of treatment. Results: Among 1436 patients, HbA1c reduced by, mean[95% CI], 1.35%[1.27,1.42] (p<0.0001) from a baseline of, mean±SD, 9.41±1.41%. Among 1381 patients, weight reduced by 3.6 kg[3.3,3.9] (p<0.0001) from a baseline of 100.2±20.7 kg. Results of univariate analyses are shown in Table 1. In multivariate analysis, higher baseline HbA1c (p<0.0001), lower CKD stage (p=0.002) and higher ALT (log transformed)(p=0.02) were associated with greater HbA1c reduction. Higher baseline weight (p<0.001) and non-insulin use (p<0.0001) were associated with greater weight reduction. Conclusion: As expected, HbA1c reduction was associated with baseline HbA1c and background renal function, while weight reduction was associated with baseline weight. The interactions between HbA1c reduction and ALT levels, and weight reduction with insulin treatment status warrant further investigations. Disclosure: K. Thong: None. J. Chung-Wah-Cheong: None. M. Yadagiri: None. M.L. Cull: None. A. Bickerton: Employee; Self; MyWay Digital Health. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. H. Reid: None. D.S. Morris: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NAPP Pharmaceuticals Limited, Novo Nordisk A/S, Sanofi-Aventis. M. Atkin: Advisory Panel; Self; NAPP Pharmaceuticals Limited. Consultant; Self; My mHealth. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. A.M. Robinson: Advisory Panel; Self; Takeda UK. D.M. Williams: None. J.W. Stephens: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, NAPP Pharmaceuticals Limited. I.W. Gallen: None. K. Adamson: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. Funding: Association of British Clinical Diabetologists [ABSTRACT FROM AUTHOR]