Table 2.
Liver-related outcome effects of treatment with GLP-1RA or DPP-4 inhibitors in humans.
| References | Subjects | Weeks of Treatment | Treatment Agent | Histology (Yes/No) | Fibrosis | Steatosis | Visceral Fat | ALT | BMI | HbA1c |
|---|---|---|---|---|---|---|---|---|---|---|
| Buse et al. (2007) [144] | T2D (n = 283) | 30 + 2 years follow up | Exenatide | No | - | - | - | ↓ (if elevated at baseline) |
↓ | ↓ |
| Klonoff et al. (2008) [110] | T2D (n = 217) | 30 + 3 years follow up | Exenatide | No | - | - | - | ↓ (if elevated at baseline) |
↓ | ↓ |
| Jendle et al. (2009) [145] | T2D (n = 131) | 26 | Liraglutide + Metformin | No | - | ↓ (CT) |
↓ (CT) |
↓ | ↓ | ↓ |
| Kenny et al. (2010) [146] | T2D and biopsy-proven NAFLD (n = 8) | 28 | Exenatide | Yes | ↓ | ↓ | - | ↓ | ↓ | ↓ |
| Sathyanarayana et al. (2011) [147] | T2D (n = 21) | 52 | Exenatide + Pioglitazone | No | - | ↓ (MRS) |
- | ↓ | ↓ | ↓ |
| Yilmaz et al. (2012) [148] | T2D+ NASH (n = 15) | 52 | Sitagliptin | Yes | = | = | - | ↓ | ↓ | = |
| Ohki et al. (2012) [149] | T2D and NAFLD (n = 26) | NA | Liraglutide | No | ↓ (APRI) |
- | - | ↓ | ↓ | ↓ |
| Ohki et al. (2012) [149] | T2D and NAFLD (n = 36) | NA | Sitagliptin | No | = (APRI) |
- | - | ↓ | = | ↓ |
| Cuthberson et al. (2012) [150] | Obese, T2D and NAFLD (n = 25, 19/6) | 26 | Exenatide or Liraglutide | No | - | ↓ (MRS) |
↓ (MRI) |
↓ | ↓ | ↓ |
| Fan et al. (2013) [151] | T2D and NAFLD (n = 117) | 12 | Exenatide or Metformin | No | - | - | - | ↓ | ↓ | = |
| Suzuki et al. (2013) [152] | T2D (n = 46) | 26 | Liraglutide + Pioglitazone | No | - | ↓ (CT) |
↓ (CT) |
- | ↓ | = |
| Bergenstal et al. (2013) [153] | T2D (n = 534) | 52 | Exenatide | No | - | - | - | ↓ | ↓ | ↓ |
| Blaslov et al. (2014) [154] | T2D (n = 125) | 26 | Exenatide alone or add-on metformin or/and sulphonylurea | No | - | ↓ (FLI) |
- | ↓ | ↓ | ↓ |
| Shao et al. (2014) [109] | Obese, NAFLD with elevated liver enzymes and T2D (n = 60) | 12 | Exenatide + Insulin | No | - | ↓ (US) |
- | ↓ | ↓ | ↓ |
| Watanabe et al. (2015) [115] | T2D and NAFLD (n = 7) | 12 | Sitagliptin | No | - | ↓ (MRS) |
= (MRI) |
= | = | ↓ |
| Tang et al. (2015) [142] | T2D (n = 35) | 12 | Liraglutide or Insulin glargine | No | - | = (MRS) |
- | = | ↓ | ↓ |
| Eguchi et al.* (2015) [155] | Diabetic NAFLD/NASH (n = 19) | 24 + 24 | Lifestyle + Liraglutide | No | ↓ (FIB-4) |
↓ (CT) |
↓ (CT) |
↓ | ↓ | ↓ |
| Eguchi et al.* (2015) [155] | T2D+ NAFLD/NASH (n = 10) | 24 + 24 + 96 | Lifestyle + Liraglutide + Follow-up Liraglutide | Yes | ↓ | ↓ | - | ↓ | ↓ | ↓ |
| Smits et al. (2016) [156] | Overweight T2D (n = 52) | 12 | Liraglutide or Sitagliptin | No | = (APRI/FIB-4/NFS) |
= (MRS) |
- | ↓ | = | ↓ |
| Cui et al. (2016) [114] | Prediabetic NAFLD (n = 50) | 24 | Sitagliptin | No | = (MRE) |
= (MRI) |
- | = | = | = |
| Armstrong et al. (2016) [103] | Biopsy-proven NASH (n = 23) | 48 | Liraglutide | Yes | ↓ | ↓ | - | ↓ | ↓ | ↓ |
| Joy et al. (2017) [116] | Biopsy-proven NASH (n = 12) | 26 | Sitagliptin | Yes | = (NAS) |
= (MRI) |
= (MRI) |
= | = | ↓ |
| Petit et al. (2017) [157] | T2D (n = 68) | 26 | Liraglutide | No | - | ↓ (MRS) |
- | ↓ | ↓ | ↓ |
| Feng et al. (2017) [158] | T2D and NAFLD (n = 87) | 24 | Liraglutide, Metformin or Gliclazide | No | - | ↓ (US) |
- | ↓ | ↓ | ↓ |
| Khoo et al. (2017) [159] | Obese NAFLD (n = 24) | 26 | Liraglutide versus Lifestyle | No | - | ↓ (MRI) |
- | ↓ | ↓ | - |
| Seko et al. (2017) [107] | T2D and biopsy-proven NAFLD (n = 15) | 12 | Dulaglutide | Yes | ↓ | ↓ | - | ↓ | ↓ | ↓ |
| Cusi et al. (2018) [106] | T2D (n = 971) | 26 | Dulaglutide | No | - | - | - | ↓ | - | ↓ |
| Yan et al. (2019) [143] | T2D and NAFLD (n = 18) | 26 | Liraglutide + Metformin | No | - | ↓ (MRI) |
↓ (MRI) |
- | ↓ | ↓ |
| Gastaldelli et al. (2019) [111] | T2D (n = 228) | 28/52 | Exenatide + Dapagliflozin | No | - | - | - | ↓ | - | ↓ |
Abbreviations: ALT, alanine aminotransferase; APRI, AST to platelet ratio index; BMI, body mass index; CT, computed tomography; FIB-4, fibrosis-4 index; HbA1c, glycosylated hemoglobin; MRE, magnetic resonance elastography; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD Activity Score; NASH, Non-alcoholic steatohepatitis; NFS, NAFLD fibrosis score; T2D, type-2 diabetes; US, ultrasound. ↓ represent a decrease; = represent no change. * 24weeks lifestyle intervention, followed by 24 weeks with liraglutide. 10 subjects continued liraglutide until 96 weeks and were followed up with biopsy. All analyses are reported versus baseline GLP-1RA/DPP-4 inhibitor.