Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: A 12-month randomized, prospective, open- label trial
Open accessAbstract
Medication combinations that improve the efficacy of thiazolidinediones or ameliorate weight-gain side effects of therapy represent an attractive potential treatment for (NASH). The aim of this randomized, open-label trial was to assess the efficacy of rosiglitazone and metformin in combination versus rosiglitazone and losartan, compared to rosiglitazone alone, after 48 weeks of therapy. A total of 137 subjects with biopsy-proven NASH were enrolled and randomly assigned to receive either 4 mg twice-daily of rosiglitazone, 4 mg of rosiglitazone and 500 mg of metformin twice-daily, or 4 mg of rosiglitazone twice-daily and 50 mg of losartan once-daily for 48 weeks. Patients were screened for other etiologies of chronic liver disease, including daily alcohol intake in excess of 20 g. Repeat liver biopsy was performed after 48 weeks of therapy and reviewed in a blinded fashion by a single expert hepatopathologist. The primary aim of the study was to assess for differences between treatment groups in the improvement of steatosis, hepatocellular inflammation, and fibrosis. In total, 108 subjects completed the trial. Primary outcome revealed no significant difference between treatment groups in all histologic parameters (steatosis, P = 0.137; hepatocellular inflammation, P = 0.320; fibrosis, P = 0.229). Overall improvement in steatosis, hepatocellular inflammation, ballooning degeneration, and fibrosis was observed (P ≤ 0.001). Serum aminotransferases were reduced in all three groups (P < 0.001 within treatment, P > 0.05 between groups). Metformin did not significantly mitigate weight gain (P = 0.051). Conclusions: Forty-eight weeks of combination therapy with rosiglitazone and metformin or rosiglitazone and losartan confers no greater benefit than rosiglitazone alone with respect to histopathology. (Hepatology 2011;)
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In patients with MASH, 48 weeks of rosiglitazone produced histological improvements comparable to rosiglitazone combined with metformin or losartan, including similar effects on steatosis, inflammation, ballooning degeneration, and fibrosis.
“48 weeks of rosiglitazone therapy, another PPARγ agonist, produced histological improvements in patients with MASH comparable to those observed with rosiglitazone combined with either metformin or losartan, including similar effects on steatosis, inflammation, ballooning degeneration, and fibrosis.”
From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [205]
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Risk of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease
Targher, G., Day, C. P., & Bonora, E. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0912063 · Cited by 1,907 · see citing works
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis
Belfort, R., Harrison, S. A., Brown, K., Darland, C., Finch, J., Hardies, J., Balas, B., Gastaldelli, A., Tio, F., Pulcini, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa060326 · Cited by 1,827 · see citing works
Self-citationAithal, G. P., Thomas, J. A., Kaye, P. V., Lawson, A., Ryder, S. D., Spendlove, I., Austin, A. S., Freeman, J. G., Morgan, L., & Webber, J. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.06.047 · Cited by 721 · see citing works
Aksnes, T. A., Reims, H. M., Guptha, S., Moan, A., Os, I., & Kjeldsen, S. E. (2006) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1002087 · Cited by 31 · see citing works
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Tilg, H., Moschen, A. R., & Roden, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.147 · Cited by 1,002 · see citing works
Duell, P. B., Welty, F. K., Miller, M., Chait, A., Hammond, G., Ahmad, Z., Cohen, D. E., Horton, J. D., Pressman, G. S., Toth, P. P., et al. (2022) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atv.0000000000000153 · Cited by 727 · see citing works
Hepatic fibrosis: concept to treatment
Trautwein, C., Friedman, S. L., Schuppan, D., & Pinzani, M. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.039 · Cited by 677 · see citing works
Azzu, V., Vacca, M., Virtue, S., Allison, M., & Vidal-Puig, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.054 · Cited by 369 · see citing works
Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action
Bril, F., & Cusi, K. (2017) · Diabetes Care · doi:10.2337/dc16-1787 · Cited by 341 · see citing works
Mantovani, A., Byrne, C. D., Scorletti, E., Mantzoros, C. S., & Targher, G. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2019.12.007 · Cited by 138 · see citing works
Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages
Aquino, J. B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1792423 · Cited by 1 · see citing works
“Subsequently, Torres et al. (205) reported that 48 weeks of rosiglitazone therapy, another PPAR g agonist, produced histological improvements in patients with MASH comparable to those observed with rosiglitazone combined with either metformin or losartan, including similar effects on steatosis, in…”
- Authors
- Torres, D. M., Jones, F. J., Shaw, J. C., Williams, C. D., Ward, J. A., & Harrison, S. A.
- Affiliations
- Walter Reed National Military Medical Center (US)
- Wilford Hall Ambulatory Surgical Center (US)
- Brooke Army Medical Center (US)
- Corresponding author
- Harrison, Stephen A.
- Venue
- Hepatology
- Published
- 2011-11
- Volume
- 54
- Issue
- 5
- Pages
- 1631-1639
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2096064097
- Cited by
- 183
- References
- 4
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 13 · 2020: 8 · 2019: 8 · 2018: 13 · 2017: 17 · 2016: 24 · 2015: 17 · 2014: 9 · 2013: 15 · 2012: 14
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nonalcoholic steatohepatitis, rosiglitazone, metformin, losartan, thiazolidinediones, combination therapy, steatosis, liver fibrosis, ballooning degeneration, transaminases, weight gain, histopathology
- MeSH terms
- Rosiglitazone, Adolescent, Adult, Aged, Biopsy, Drug Therapy, Combination, Fatty Liver, Female, Humans, Hypoglycemic Agents, Liver, Male, Metformin, Middle Aged, Prospective Studies, Treatment Outcome, Losartan, Thiazolidinediones, Angiotensin II Type 1 Receptor Blockers, Young Adult, Non-alcoholic Fatty Liver Disease
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