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Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes
Open accessAbstract
Both rosiglitazone and metformin increase hepatic insulin sensitivity, but their mechanism of action has not been compared in humans. The objective of this study was to compare the effects of rosiglitazone and metformin treatment on liver fat content, hepatic insulin sensitivity, insulin clearance, and gene expression in adipose tissue and serum adiponectin concentrations in type 2 diabetes. A total of 20 drug-naive patients with type 2 diabetes (age 48 +/- 3 years, fasting plasma glucose 152 +/- 9 mg/dl, BMI 30.6 +/- 0.8 kg/m2) were treated in a double-blind randomized fashion with either 8 mg rosiglitazone or 2 g metformin for 16 weeks. Both drugs similarly decreased HbA1c, insulin, and free fatty acid concentrations. Body weight decreased in the metformin (84 +/- 4 vs. 82 +/- 4 kg, P < 0.05) but not the rosiglitazone group. Liver fat (proton spectroscopy) was decreased with rosiglitazone by 51% (15 +/- 3 vs. 7 +/- 1%, 0 vs. 16 weeks, P = 0.003) but not by metformin (13 +/- 3 to 14 +/- 3%, NS). Rosiglitazone (16 +/- 2 vs. 20 +/- 1 ml.kg(-1).min(-1), P = 0.02) but not metformin increased insulin clearance by 20%. Hepatic insulin sensitivity in the basal state increased similarly in both groups. Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin. Serum adiponectin concentrations increased by 123% with rosiglitazone but remained unchanged during metformin treatment. The decrease of serum adiponectin concentrations correlated with the decrease in liver fat (r = -0.74, P < 0.001). Rosiglitazone but not metformin significantly increased expression of peroxisome proliferator-activated receptor-gamma, adiponectin, and lipoprotein lipase in adipose tissue. In conclusion, rosiglitazone but not metformin decreases liver fat and increases insulin clearance. The decrease in liver fat by rosiglitazone is associated with an increase in serum adiponectin concentrations. Both agents increase hepatic insulin sensitivity, but only rosiglitazone increases peripheral glucose uptake.
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“Reductions in hepatic steatosis with both pioglitazone and rosig litazone ameliorate hepatic insulin resistance.134,135”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [135]
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“We have previously shown that metformin does not change liver fat content.35”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [35]
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Metadata
- Authors
- Tiikkainen, M., Häkkinen, A.-M., Korsheninnikova, E., Nyman, T., Mäkimattila, S., & Yki-Järvinen, H.
- Affiliations
- University of Helsinki (FI)
- Department of Medicine, Division of Oncology, University of Helsinki, Helsinki, Finland
- Minerva Foundation (FI)
- Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-08-01
- Volume
- 53
- Issue
- 8
- Pages
- 2169-2176
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2107068945
- Cited by
- 524
- References
- 48
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 14 · 2020: 16 · 2019: 6 · 2018: 15 · 2017: 12 · 2016: 18 · 2015: 19 · 2014: 24 · 2013: 26 · 2012: 15
- FWCI
- 34.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Suomen Lääketieteen Säätiö
- Biomedicum Helsinki-säätiö
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- rosiglitazone, metformin, type 2 diabetes, hepatic insulin resistance, hepatic insulin sensitivity, liver fat, insulin clearance, adiponectin, adipose tissue gene expression, PPARγ, lipoprotein lipase, insulin-stimulated glucose uptake, 1H NMR, drug comparison, weight loss, HbA1c
- MeSH terms
- Rosiglitazone, Adipose Tissue, Cholesterol, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Liver, Male, Metformin, Middle Aged, Triglycerides, Thiazolidinediones, Lipid Metabolism
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