Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program
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 parameter...
| Автори: | , , , , , , , |
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| Формат: | Journal article |
| Мова: | English |
| Опубліковано: |
2013
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| _version_ | 1826301177755598848 |
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| author | Armstrong, M Houlihan, D Rowe, I Clausen, W Elbrønd, B Gough, S Tomlinson, J Newsome, P |
| author_facet | Armstrong, M Houlihan, D Rowe, I Clausen, W Elbrønd, B Gough, S Tomlinson, J Newsome, P |
| author_sort | Armstrong, M |
| collection | OXFORD |
| description | 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 HbA1c (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. © 2012 Blackwell Publishing Ltd. |
| first_indexed | 2024-03-07T05:28:26Z |
| format | Journal article |
| id | oxford-uuid:e15c3c99-c80a-4817-a60c-e85be12bc810 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:28:26Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:e15c3c99-c80a-4817-a60c-e85be12bc8102022-03-27T09:53:58ZSafety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD programJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e15c3c99-c80a-4817-a60c-e85be12bc810EnglishSymplectic Elements at Oxford2013Armstrong, MHoulihan, DRowe, IClausen, WElbrønd, BGough, STomlinson, JNewsome, PBackground 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 HbA1c (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. © 2012 Blackwell Publishing Ltd. |
| spellingShingle | Armstrong, M Houlihan, D Rowe, I Clausen, W Elbrønd, B Gough, S Tomlinson, J Newsome, P Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program |
| title | Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program |
| title_full | Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program |
| title_fullStr | Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program |
| title_full_unstemmed | Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program |
| title_short | Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program |
| title_sort | 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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