Reductions in alanine aminotransferase levels with liraglutide treatment are greatest in those with raised baseline levels and are independent of weight loss: real-world outcome data from the ABCD Nationwide Liraglutide Audit

Authors

  • Thomas SJ Crabtree City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK Royal Derby Hospital, University Hospitals of Derby and Burton NHS Trust, Derby, UK University of Nottingham, UK
  • Susannah Rowles Pennine Acute Hospitals NHS Trust, Manchester, UK
  • Stephanie Tarpey Pennine Acute Hospitals NHS Trust, Manchester, UK
  • Adele Kennedy Antrim Area Hospital, Northern Ireland, UK Causeway Hospital, Coleraine, UK
  • John Chalmers Victoria Hospital, Kirkcaldy, UK
  • Rahul Nayar City Hospitals Sunderland NHS Foundation Trust, Sunderland, UK
  • Amanda Lee City Hospitals Sunderland NHS Foundation Trust, Sunderland, UK
  • Ken Darzy Queen Elizabeth II Hospital, Welwyn Garden City, UK
  • Peter Winocour Queen Elizabeth II Hospital, Welwyn Garden City, UK
  • John Lindsay Altnagelvin Area Hospital, Northern Ireland, UK
  • Iskandar Idris Royal Derby Hospital, University Hospitals of Derby and Burton NHS Trust, Derby, UK University of Nottingham, UK
  • Ken Y Thong School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
  • Piya Sen Gupta King's College Hospital, London, UK
  • Amar Puttanna Diabetes and Endocrinology, Good Hope Hospital, West Midlands
  • Pranav Kumar Newcross Hospital, Wolverhampton, UK
  • Robert EJ Ryder City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK
  • On Behalf of ABCD Nationwide Audit Contributors

DOI:

https://doi.org/10.15277/bjd.2019.227

Keywords:

liraglutide, non-alcoholic fatty liver disease, alanine aminotransferase (ALT), type 2 diabetes mellitus

Abstract

People with type 2 diabetes mellitus experience an increased prevalence of non-alcoholic fatty liver disease (NAFLD) compared with the general population and often with worse outcomes. As part of the ABCD Liraglutide Nationwide Audit Programme, we obtained and analysed data from 2009 to 2018 to assess the impact of liraglutide on alanine aminotransferase (ALT) levels as a marker of liver inflammation (often used in clinical trials as a marker of NAFLD). After excluding those with insufficient or incomplete data, we analysed the results from 1,759 patients treated in the real-world clinical setting. Our results demonstrated an overall significant decrease in median ALT (−1 U/L, 95% CI −1 to −2, p<0.001) compared with baseline, which was more pronounced in patients with elevated ALT based on gender- specific ranges (male: −4 U/L, 95% CI −3 to −6, p<0.001; female: −3 U/L, 95% CI −2 to −4, p<0.001). There was no correlation between weight loss and degree of ALT change (rho=−0.0002, p=0.41). Our data mirror outcomes from large randomised controlled trials and show that the impact of liraglutide on ALT is likely generalisable to real-world practice. Some of our data suggest that there may be a slight increase in ALT in those with normal levels at baseline, although the clinical significance of this is uncertain.

Author Biography

Thomas SJ Crabtree, City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK Royal Derby Hospital, University Hospitals of Derby and Burton NHS Trust, Derby, UK University of Nottingham, UK

Diabetes Research Fellow

References

Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism 2016;65(8):1096–108. https://doi.org/10.1016/j.metabol.2016.01.001

Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015;313(22):2263–73. https://doi.org/10.1001/jama.2015.5370

Targher G, Marchesini G, Byrne CD. Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: causal association or epiphenomenon? Diabetes Metab 2016;42(3):142–56. https://doi.org/10.1016/j.diabet.2016.04.002

Sung KC, Wild SH, Byrne CD. Resolution of fatty liver and risk of incident diabetes. J Clin Endocrinol Metab 2013;98(9):3637–43. https://doi.org/10.1210/jc.2013-1519

Bril F, Cusi K. Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action. Diabetes Care 2017;40(3):419–30. https://doi.org/10.2337/dc16-1787

Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30(5):1212–18. https://doi.org/10.2337/dc06-2247

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO). Clinical practice guidelines for the management of non-alcoholic fatty liver disease. Obes Facts 2016;9(2):65–90. https://doi.org/10.1159/000443344

Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012;55(4):885–904. https://doi.org/10.1007/s00125-011-2446-4

Suzuki A, Lymp J, St Sauver J, Angulo P, Lindor K. Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis. Liver Int 2006;26(10):1209–16. https://doi.org/10.1111/j.1478-3231.2006.01362.x

Ballestri S, Nascimbeni F, Romagnoli D, Lonardo A. The independent predictors of non-alcoholic steatohepatitis and its individual histological features: insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment. Hepatol Res 2016;46(11):1074–87. https://doi.org/10.1111/hepr.12656

Armstrong MJ, Houlihan DD, Rowe IA, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Therap 2013;37(2):234–42. https://doi.org/10.1111/apt.12149

Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387(10019):679–90. https://doi.org/10.1016/S0140-6736(15)00803-X

Feng W, Gao C, Bi Y, et al. Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease. J Diabetes 2017; 9(8):800–9. https://doi.org/10.1111/1753-0407.12555

Tian F, Zheng Z, Zhang D, He S, Shen Jl. Efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease. Biosci Rep 2018;38(6). https://doi.org/10.1042/BSR20181304

Ohki T, Isogawa A, Iwamoto M, et al. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone. Scientific World Journal 2012;2012:496453. https://doi.org/10.1100/2012/496453

Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007;29(1):139–53. https://doi.org/10.1016/j.clinthera.2007.01.015

Prati D, Taioli E, Zanella A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002;137(1):1–10. https://doi.org/10.7326/0003-4819-137-1-200207020-00006

National Institute for Health and Care Excellence (NICE). Type 2 diabetes in adults: management [NG28]. 2015. Available from: www.nice.org.uk/guidance/ng28/ (accessed 15 August 2019).

Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7(10):1104–12. https://doi.org/10.1016/j.cgh.2009.05.033

Dumitrascu DL, Neuman MG. Non-alcoholic fatty liver disease: an update on diagnosis. Clujul Med 2018; 91(2):147–50. https://doi.org/10.15386/cjmed-993

Gimeno-Orna JA, Verdes-Sanz G, Borau-Maorad L, et al. Baseline ALT levels as a marker of glycemic response to treatment with GLP-1 receptor agonists. Endocrinol Nutr 2016;63(4): 164–70. https://doi.org/10.1016/j.endonu.2015.11.009

Downloads

Published

2019-12-17

Issue

Section

Original Research

Most read articles by the same author(s)

1 2 3 4 5 6 > >>