Dulaglutide decreases plasma aminotransferases in people with type 2 diabetes in a pattern consistent with liver fat reduction: a post hoc analysis of the AWARD programme

Cusi, K., Sattar, N. , García-Pérez, L.-E., Pavo, I., Yu, M., Robertson, K. E., Karanikas, C. A. and Haupt, A. (2018) Dulaglutide decreases plasma aminotransferases in people with type 2 diabetes in a pattern consistent with liver fat reduction: a post hoc analysis of the AWARD programme. Diabetic Medicine, 35(10), pp. 1434-1439. (doi: 10.1111/dme.13697) (PMID:29869810)

Abstract

Aims: To evaluate the effects of dulaglutide vs placebo on liver and glycaemic/metabolic measurements in a population with Type 2 diabetes and in a subgroup with non‐alcoholic fatty liver/non‐alcoholic steatohepatitis. Methods: A total of 1499 participants from AWARD‐1, AWARD‐5, AWARD‐8 and AWARD‐9 clinical trials were included in this analysis (dulaglutide 1.5 mg, n=971 and placebo, n=528). Thresholds of alanine aminotransferase levels ≥30 IU/l in men and ≥19 IU/l in women were used to determine the subgroup who had non‐alcoholic fatty liver/non‐alcoholic steatohepatitis. Objectives included changes from baseline to 6 months in: (1) alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels in the overall population and (2) alanine aminotransferase, aspartate transaminase, gamma‐glutamyl transpeptidase and glycaemic/metabolic measurements (e.g. HbA1c, fasting serum glucose, body weight, lipids and homeostatic model assessment) in the non‐alcoholic fatty liver/non‐alcoholic steatohepatitis subgroup. Results: In the overall population at 6 months, dulaglutide significantly reduced alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels vs placebo [least squares mean treatment differences: –1.7 IU/l (95% CI –2.8, –0.6), P=0.003; –1.1 IU/l (95% CI –2.1, –0.1), P=0.037; –6.6 IU/l (95% CI –12.4, –0.8), P=0.025, respectively]. In the subgroup with non‐alcoholic fatty liver/non‐alcoholic steatohepatitis (alanine aminotransferase levels greater than or equal to the upper limit of normal), mean baseline liver enzyme values were 38.0 IU/l, 27.8 IU/l and 43.9 IU/l for alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase, respectively. In this population, more pronounced reductions from baseline in alanine aminotransferase were observed with dulaglutide vs placebo (–8.8 IU/l vs –6.7 IU/l). In the subgroup of people with alanine aminotransferase levels less than the upper limit of normal, changes from baseline in alanine aminotransferase did not significantly differ between treatment groups (0.0 IU/l vs 0.7 IU/l). Conclusions: Once‐weekly dulaglutide improved alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels compared with placebo in a pattern consistent with liver fat reductions. Our results add further weight to the notion that glucagon‐like peptide‐1 receptor agonists may provide benefit in lowering liver fat in addition to their other metabolic actions.

• Item Type: Articles
• Additional Information: This work was sponsored by Eli Lilly and Company.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Cusi, K., Sattar, N., García-Pérez, L.-E., Pavo, I., Yu, M., Robertson, K. E., Karanikas, C. A., and Haupt, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetic Medicine
• Publisher: Wiley
• ISSN: 0742-3071
• ISSN (Online): 1464-5491
• Published Online: 22 June 2018