Joint senior authors.
Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program
Article first published online: 19 NOV 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 37, Issue 2, pages 234–242, January 2013
How to Cite
Armstrong, M. J., Houlihan, D. D., Rowe, I. A., Clausen, W. H. O., Elbrønd, B., Gough, S. C. L., Tomlinson, J. W. and Newsome, P. N. (2013), Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Alimentary Pharmacology & Therapeutics, 37: 234–242. doi: 10.1111/apt.12149
- Issue published online: 17 DEC 2012
- Article first published online: 19 NOV 2012
- Manuscript Revised: 30 OCT 2012
- Manuscript Accepted: 30 OCT 2012
- Manuscript Revised: 29 OCT 2012
- Manuscript Received: 5 OCT 2012
- Novo Nordisk
Non-alcoholic fatty liver disease has reached epidemic proportions in type 2 diabetes (T2D). Glucagon-like peptide-1 analogues are licensed in T2D, yet little data exist on efficacy and safety in liver injury.
To assess the safety and efficacy of 26-week liraglutide on liver parameters in comparison with active-placebo.
Individual patient data meta-analysis was performed using patient-level data combined from six 26-week, phase-III, randomised controlled T2D trials, which comprise the ‘Liraglutide Effect and Action in Diabetes’ (LEAD) program. The LEAD-2 sub-study was analysed to assess the effect on CT-measured hepatic steatosis.
Of 4442 patients analysed, 2241 (50.8%) patients had an abnormal ALT at baseline [mean ALT 33.8(14.9) IU/L in females; 47.3(18.3) IU/L in males]. Liraglutide 1.8 mg reduced ALT in these patients vs. placebo (−8.20 vs. −5.01 IU/L; P = 0.003), and was dose-dependent (no significant differences vs. placebo with liraglutide 0.6 or 1.2 mg). This effect was lost after adjusting for liraglutide's reduction in weight (mean ALT difference vs. placebo −1.41 IU/L, P = 0.21) and HbA1c (+0.57 IU/L, P = 0.63). Adverse effects with 1.8 mg liraglutide were similar between patients with and without baseline abnormal ALT. In LEAD-2 sub-study, liraglutide 1.8 mg showed a trend towards improving hepatic steatosis vs. placebo (liver-to-spleen attenuation ratio +0.10 vs. 0.00; P = 0.07). This difference was reduced when correcting for changes in weight (+0.06, P = 0.25) and HbA1c (0.00, P = 0.93).
Twenty-six weeks' liraglutide 1.8 mg is safe, well tolerated and improves liver enzymes in patients with type 2 diabetes. This effect appears to be mediated by its action on weight loss and glycaemic control.