Clinical studies investigating the impact of tirzepatide on MASLD/MASH, listed in chronological order.
| Author, year [ref.] | Method | Results | Conclusion |
|---|---|---|---|
| Gastaldelli et al., 2022 [40] | 296 individuals with an FLI ≥ 60 out of 502 T2DM subjects enrolled in the SURPASS-3 trial were submitted to MRI scanning and were randomised (1:1:1:1) in the main study to s.c. tirzepatide (5 mg, 10 mg, or 15 mg) once weekly or s.c. insulin degludec once daily, using an interactive web-response system, and were stratified by country, HbA1c, and concomitant oral anti-diabetic drugs. | At week 52, the absolute decrease in LFC was significantly greater for the pooled 10 mg and 15 mg tirzepatide groups (–8.09%, SE 0.57) vs. the insulin degludec group (–3.38%, SE 0.83). The estimated treatment difference versus insulin degludec was –4.71% (95% CI –6.72 to –2.70; p < 0.0001). Among individuals randomized to tirzepatide, the decreased LFC was significantly correlated (p ≤ 0.0006) with baseline LFC (ρ = –0.71), reductions in VAT (ρ = 0.29), reductions in ASAT (ρ = 0.33), and reductions in BW (ρ = 0.34). | In this subpopulation of T2DM patients in the SURPASS-3 study, the use of tirzepatide compared to insulin degludec was associated with significantly reduced LFC, VAT, and ASAT. |
| Loomba et al., 2024 [10] | Phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving 190 participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis who were randomized to once-weekly s.c. tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. The primary endpoint was MASH resolution without worsening of fibrosis at 52 weeks. The secondary endpoint was a decrease of ≥ 1 fibrosis stage without worsening of MASH. | At week 52, liver biopsies of 157 among 190 randomized participants could be evaluated, with missing values imputed under the assumption that they would follow the pattern of results in the placebo group. The proportion of enrollees who exhibited MASH resolution without worsening of fibrosis was 10% in the placebo group, 44% in the 5-mg tirzepatide group (difference vs. placebo, 34 percentage points; 95% CI, 17 to 50), 56% in the 10-mg tirzepatide group (difference, 46 percentage points; 95% CI, 29 to 62), and 62% in the 15-mg tirzepatide group (difference, 53 percentage points; 95% CI, 37 to 69) (p < 0.001 for all three comparisons). The fraction of individuals showing an improvement of ≥ 1 fibrosis stage without MASH worsening was 30% vs. 55% in the placebo group, vs. the 5-mg tirzepatide group, respectively (difference vs. placebo, 25 percentage points; 95% CI, 5 to 46), 51% in the 10-mg tirzepatide group (difference, 22 percentage points; 95% CI, 1 to 42), and 51% in the 15-mg tirzepatide group (difference, 21 percentage points; 95% CI, 1 to 42). The most common adverse events in the tirzepatide groups were GI events, and most were mild or moderate. | Tirzepatide treatment for 52 weeks is more effective than placebo in resolving MASH without worsening fibrosis. |
| Sawamura et al., 2024 [41] | Retrospective analysis at months 3 and 6 after the switch of data from 40 T2DM patients who received a prescription change from dulaglutide to tirzepatide. | Six months after the treatment switch, average reductions of 1.2% and 3.6 kg were observed in HbA1c and BW, respectively. The change in HbA1c was negatively correlated with the baseline HbA1c value. However, BW reduction was observed regardless of baseline features. Moreover, AST, ALT, and GGT values decreased 6 months after the switch. The FIB-4 did not improve during the study period. | Among T2DM patients, switching from dulaglutide to tirzepatide treatment has beneficial effects on blood glucose level, BW, and liver enzymes. |
| Ferch et al., 2025 [42] | Report of two cases living with AS who were treated with tirzepatide.SLD was assessed with MRI. | The first subject, with 18 months on treatment, experienced weight loss of –28 kg (113.6 kg to 83 kg, –26.9%); HbA1c decreased by –0.4% (6.7% to 6.3%), with considerable reductions in daily insulin doses. SLD resolved from a previous fat fraction of 20%. The second individual was followed up for 9 months and showed a weight reduction of –9.5 kg (132 kg to 122.5 kg; –7.2%) with a reduction of LFC from 21% to 11% after ~3 months of therapy. | In the rare, genetic, multi-systemic disorder AS, tirzepatide treatment is associated with a significant reduction in BW, IR, and LFC. |
| Sattar et al., 2025 [43] | Post-hoc, sub-study analysis of 296 individuals in whom thigh muscle fat infiltration, muscle volume, and muscle volume Z score were assessed by MRI at baseline and week 52 out of 502 T2DM participants enrolled in the SURPASS-3 trial who were randomly assigned (1:1:1:1) to receive s.c. (5, 10, or 15 mg) tirzepatide once weekly, or daily s.c.insulin degludec. | At week 52 compared to the baseline value, significant reductions were observed in muscle fat infiltration for the pooled and individual tirzepatide dose groups (for pooled tirzepatide, mean change –0.36 percentage points [95% CI –0.48 to –0.25, p < 0.0001], muscle volume [–0.64 L (95% CI –0.74 to –0.54, p < 0.0001)], and muscle volume Z score [–0.22 (95% CI –0.29 to –0.15), p < 0.0001], which occurred in the context of significant BW reduction. Conversely, treatment with insulin degludec was associated with increased BW and muscle volume. | Tirzepatide (but not insulin degludec) treatment was associated with potentially favorable changes in muscle fat infiltration and reductions in muscle volume. |
| Okuma et al., 2025 [44] | Retrospective study of a cohort of 54 Japanese with T2DM and MASLD submitted to a treatment switching from a GLP-1RA to tirzepatide. | Six months after the treatment switch, BW, HbA1c, FLI, FIB-4, and hsCRP levels were observed. MRA disclosed age, T2DM duration, and pre-switch HbA1c levels independently predicted BW loss while pre-switch age predicted a decrease in FLI. | Switching from GLP-1RAs to tirzepatide among Japanese T2DM subjects with MASLD is effective, and predictors of BW loss and FLI decrease after switching to tirzepatide are identifiable. |
| Oe et al., 2025 [45] | Case study. | A 50-year-old man with a 16-year history of poorly controlled T2DM diabetes had elevated liver enzymes and histologically proven MASH. Liraglutide was administered for 3 years but his liver function and glycemic control deteriorated gradually, and a second liver biopsy found cirrhosis. At this point, liraglutide was switched to tirzepatide. Over 6 months of tirzepatide administration, the patient’s HbA1c and liver enzymes decreased. A third biopsy performed at this point showed markedly improved histology, including ameliorated liver fibrosis. | Severe MASH improved after switching from GLP-1RA treatment to tirzepatide. |
| Souza et al., 2025 [46] | Network meta-analysis of 29 RCTs totaling 9,324 cases. | Tirzepatide was significantly superior to placebo at achieving the regression of liver fibrosis without MASH worsening and MASH resolution without worsening of liver fibrosis. | By providing updated data on MASH drug therapies for fibrosis regression and resolution, this study may inform clinical practice and trial design. |
| Wang et al., 2025 [47] | Systematic review and meta-analysis of 25 RCTs totaling 2,600 patients. | GLP-1RAs treatment for a median of 24 weeks induced a significant reduction in LFC by 5.21%. Moreover, significant histological improvements in steatosis, hepatocellular ballooning, and lobular inflammation were observed, with stronger evidence for tirzepatide compared to semaglutide and liraglutide. | In MASLD and MASH, tirzepatide treatment is associated with decreased LFC and improved liver histology without worsening fibrosis. |
ALT: alanine aminotransferase; AS: Alström syndrome; ASAT: abdominal subcutaneous adipose tissue; AST: aspartate aminotransferase; BW: body weight; CI: confidence interval; FIB-4: fibrosis-4 index; FLI: fatty liver index; GGT: γ-glutamyl transpeptidase; HbA1c: glycated hemoglobin; GI: gastrointestinal; GLP-1RA: glucagon-like peptide 1 receptor agonist; hsCRP: high-sensitivity C-reactive protein; IR: insulin resistance; LFC: liver fat content; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; MRA: multiple regression analysis; MRI: magnetic resonance imaging; RCTs: randomized controlled trials; s.c.: subcutaneous; SE: standard error; SLD: steatotic liver disease; T2DM: type 2 diabetes mellitus; VAT: visceral adipose tissue.