Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis
Open accessAbstract
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH. AIM: To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH. METHODS: Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index. RESULTS: Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement. CONCLUSION: Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.
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Small and uncontrolled initial trials of metformin have shown an ALT reduction and an insulin-sensitising effect, but were not followed by sufficiently large and well-conducted RCTs.
“Small and uncontrolled initial trials of metformin have shown an ALT reduction and an insulin-sensitising effect, 428,429 but were not followed by suf fi ciently large and well-conducted RCTs.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [429]
The Discussion describes this as a small, open-label trial in patients with NASH and reports improved insulin sensitivity and decreased aminotransferase levels in a subset. The Biochemical results qualify the ALT finding: the overall mean change was not statistically significant. The Discussion calls for a future placebo-controlled comparison, but the paper cannot establish the claim that the initial trials were not subsequently followed by sufficiently large, well-conducted RCTs. (LLM, conf=0.85)
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- Authors
- LOOMBA, R., LUTCHMAN, G., KLEINER, D. E., RICKS, M., FELD, J. J., BORG, B. B., MODI, A., NAGABHYRU, P., SUMNER, A. E., LIANG, T. J., & HOOFNAGLE, J. H.
- Affiliations
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Cancer Institute (MY)
- National Institutes of Health (US)
- Corresponding author
- HOOFNAGLE, J. H.
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2008-12-16
- Volume
- 29
- Issue
- 2
- Pages
- 172-182
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- PMC
- PMC2990687
- OpenAlex
- W1978128204
- Cited by
- 299
- References
- 26
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 15 · 2023: 22 · 2022: 17 · 2021: 12 · 2020: 19 · 2019: 15 · 2018: 20 · 2017: 22 · 2016: 21 · 2015: 30 · 2014: 18 · 2013: 18 · 2012: 15
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK075013)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- metformin, nonalcoholic steatohepatitis, insulin sensitivity, insulin resistance, weight loss, alanine aminotransferase, liver histopathology, hepatic steatosis, body composition
- MeSH terms
- Adult, Biopsy, Fatty Liver, Female, Humans, Hypoglycemic Agents, Liver, Male, Metformin, Middle Aged, Pilot Projects, Statistics as Topic, Treatment Outcome
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