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J Pharmacol Sci. 2003 Dec;93(4):501-4.
Metformin protects against carbon tetrachloride hepatotoxicity in mice.

Poon MK, Chiu PY, Mak DH, Ko KM.

Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, China.

In the present study, the hepatoprotective effect of metformin (Met), a dimethylbiguanide anti-hyperglycemic, was examined in a mouse model of liver damage induced by chronic repeated administration of carbon tetrachloride (CCl(4)) (5 microl/kg, twice a week for 12 weeks). Met, when given orally in drinking water at an estimated daily dose of 25 or 50 mg/kg for 10 weeks starting 2 weeks after CCl(4) challenge, protected against CCl(4) hepatotoxicity. The results indicate that the hepatoprotection afforded by Met treatment at a dose of 25 mg/kg against CCl(4) toxicity may at least in part be mediated by the enhancement of mitochondrial glutathione redox status.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14737024&dopt=Abstract [PubMed - in process]

tin.it

BACKGROUND AND AIMS: Increased mortality in diabetic patients treated with combinations of high doses of sulfonylureas and metformin was recently reported. This study was aimed at the assessment of mortality in patients treated with low-dose combinations of sulfonylureas and biguanides. METHODS: An observational cohort study was performed on a consecutive series of 927 outpatients with type 2 diabetes mellitus. Of these patients, 376 were treated with combinations of sulfonylureas (mean daily dose +/- SD: 7.3 +/- 3.2 mg for glibenclamide, and 338 +/- 79 mg for chlorpropamide) and biguanides (daily dose: 1.1 +/- 0.3 g for metformin, 60.1 +/- 19.6 mg for phenformin). Mortality was assessed through a search in the City of Florence Registry Office, with an average follow-up of 55.1 months. RESULTS: After adjusting for other potential confounders (including age, duration of diabetes, BMI, hypertension, lipid profile, HbA1c, and insulin treatment), mortality was significantly higher in patients treated with combinations of sulfonylureas and biguanides than in the rest of the sample, (relative risk, RR: 2.08; 95% confidence interval, CI 1.18-3.67, and RR: 1.68; 95%CI 1.01-2.79 among women and men, respectively). CONCLUSIONS: A higher mortality was observed in patients treated with combinations of sulfonylureas and biguanides, even at low doses. Safety of such combinations deserves further investigation. Copyright 2003 John Wiley & Sons, Ltd.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14737744&dopt=Abstract [PubMed - in process]

sanmsum.org

The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14739053&dopt=Abstract [PubMed - in process]





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