Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta‐analysis of the LEAD program

Nov 21, 2012Alimentary pharmacology & therapeutics

Safety and effectiveness of liraglutide in type 2 diabetes patients with high liver enzyme levels

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Abstract

Liraglutide 1.8 mg reduced abnormal ALT levels by 8.20 IU/L compared to placebo over 26 weeks.

Of the 4442 patients analyzed, 50.8% had an abnormal ALT level at baseline.
The reduction in ALT with liraglutide was dose-dependent, with no significant differences observed at lower doses.
The initial ALT reduction associated with liraglutide diminished after accounting for weight loss and glycemic control.
Liraglutide showed a trend toward improving liver fat content, indicated by a higher liver-to-spleen attenuation ratio compared to placebo.
The improvement in liver fat content was also reduced when considering changes in weight and HbA1c.

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BACKGROUND: 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.

AIM: To assess the safety and efficacy of 26-week liraglutide on liver parameters in comparison with active-placebo.

METHODS: 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.

RESULTS: 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 HbA(1c) (0.00, P = 0.93).

CONCLUSIONS: 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.

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Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta‐analysis of the LEAD program

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