TABLE 2.
Clinical trials concerning GLP-1 receptor agonists and liver disease
| References | Agent | Phase | Size/duration | Primary endpoint | Inflammation | Fibrosis |
|---|---|---|---|---|---|---|
| GLP-1 receptor agonists | ||||||
| Armstrong et al76 | Liraglutide, daily sc. | 2 | 52 patients, 48 wk | Resolution of MASH with no worsening of liver fibrosis | MASH resolution with no worsening of fibrosis: 39% in liraglutide group 9% in placebo group p=0.019 |
Improvement in fibrosis stage with no worsening in MASH: 26% in liraglutide 14% in placebo p=0.46 |
| Newsome et al77 | Semaglutide, daily sc. | 2 | 320 patients, 72 wk | Resolution of MASH with no worsening of liver fibrosis | MASH resolution with no worsening of liver fibrosis: 40% in 0.1 mg group 36% in 0.2 mg group 59% in 0.4 mg group 17% in placebo group p<0.001 |
Improvement in fibrosis stage with no worsening in MASH: 43% in 0.4 mg group 33% in placebo group p=0.48 |
| Loomba et al78 | Semaglutide, weekly sc. | 2 | 71 patients, 48 wk | Improvement in liver fibrosis without worsening of MASH | Resolution of MASH: 34% in semaglutide group 21% in placebo group p=0.29 |
Improvement in fibrosis stage with no worsening of MASH: 11% in semaglutide group 29% in placebo group p=0.087 |
| Ongoing phase 3 clinical trials concerning GLP-1 receptor agonists and liver disease | ||||||
| ESSENCE (NCT04822181) | Semaglutide, weekly sc. | 3 | 1200 | Resolution of steatohepatitis and no worsening of liver fibrosis. Improvement in liver fibrosis and no worsening of steatohepatitis. Time to first liver-related event |
Recruiting | Recruiting |
| Dual agonists | ||||||
| Loomba et al41 | Tirzepatide, weekly sc. | 2 | 190 | Resolution of MASH without worsening of fibrosis | MASH resolution with no worsening of fibrosis: 44% in 5 mg group 56% in 10 mg group 62% in 15 mg group 10% in placebo group p<0.001 |
Improvement of ≥1 fibrosis stage with no worsening of MASH; 55% in 5 mg group 51% in 10 mg group 51% in 15 mg group 30% in placebo group |
| Sanyal et al42 | Survodutide, weekly sc. | 2 | 293 | Improvement in MASH with no worsening of fibrosis | Improvement in MASH with no worsening of fibrosis: 47% in 2.4 mg group 62% in 4.8 mg group 43% in 6.0 mg group 14% in placebo group |
Improvement in fibrosis with no worsening of MASH: 34% in 2.4 mg group 36% in 4.8 mg group 34% in 6.0 mg group 22% in placebo group |
Note: We searched Medline for full papers published in any language in peer-reviewed journals up to January 3, 2024. We added the terms “GLP-1” and “liver disease” and filtered by “clinical trial” and identified 58 papers. These papers were manually reviewed and included if their primary endpoint was related to GLP-1 receptor agonists and SLD, used biopsies and were RCTs. We identified 3 papers reporting results of randomized controlled trials of GLP-1 receptor agonists in patients with SLD.
For phase 3 clinical trials, we searched clinicaltrials.gov and clinicaltrialsregister.eu for currently ongoing trials. We added the terms “GLP-1” and “liver disease.” We included the ongoing trials if their primary endpoint was related to GLP-1 receptor agonists and SLD and used biopsies. We identified 1 ongoing phase 3 trials using GLP-1 receptor agonists in patients with SLD.
Abbreviations: GLP-1, glucagon-like peptide 1; MASH, metabolic dysfunction–associated steatohepatitis.