The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease

Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, 5. sokak No: 48, Bahcelievler, 06490, Ankara, Turkey.
Acta Diabetologica (Impact Factor: 2.4). 11/2008; 46(2):113-8. DOI: 10.1007/s00592-008-0067-2
Source: PubMed


Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.

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    • "g/day) alone or in association with vitamin E [94] or lifestyle intervention [75, 78, 84]. Only three open-label studies have found no benefits of metformin treatment on aminotransferase levels and IR markers [85–87]. However, only few studies shown an improvement in liver histology [77, 78, 81, 83]. "
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    ABSTRACT: Insulin resistance is a clinical condition shared by many diseases besides type 2 diabetes (T2DM) such as obesity, polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). Experimental evidence, produced over the years, suggests that metformin has many benefits in the treatment of these diseases. Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance. Moreover, a number of studies have established the favorable effect of metformin on body weight, not only when evaluating BMI, but also if body mass composition is considered, through the reduction of fat mass. In addition, it reduces insulin resistance, hyperinsulinemia, lipid parameters, arterial hypertension and endothelial dysfunction. In particular, a new formulation of metformin extended-release (ER) is now available with different formulation in different countries. Metformin ER delivers the active drug through hydrated polymers which expand safe uptake of fluid, prolonging gastric transit and delaying drug absorption in the upper gastrointestinal tract. In addition, Metformin ER causes a small, but statistically significant decrease in BMI, when added to a lifestyle intervention program in obese adolescents. Because of the suggested benefits for the treatment of insulin resistance in many clinical conditions, besides type 2 diabetes, the prospective exists that more indications for metformin treatment are becoming a reality.
    Eating and weight disorders: EWD 07/2014; 19(3). DOI:10.1007/s40519-014-0139-y · 0.79 Impact Factor
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    • "Two RCTs (n ¼ 144) evaluated the effect of metformin on radiological and biochemical indices of NAFLD alone [Nar and Gedik, 2009; Bugianesi et al. 2005] Bugianesi and colleagues showed that metformin normalized aminotransferases in 69% versus 31% in the dietary therapy group (p ¼ 0.0003) [Bugianesi et al. 2005]. However, in the trial by Nar and Gedik, biochemical and radiological improvement was nonsignificant compared with diet plus exercise [Nar and Gedik, 2009]. Overall, when added to lifestyle intervention, metformin enhanced weight loss (mean weight loss 4.3—7.9%) "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, which includes dyslipidemia, central obesity, hypertension, and insulin resistance. These diseases collectively and individually increase the risk of cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is a subset of NAFLD that can progress to cirrhosis in up to 30% of patients and lead to decompensated liver disease requiring liver transplantation in many patients. Insulin resistance is the pathophysiological hallmark of NASH and addressing insulin resistance is an important aspect of NASH management. Lifestyle modifications with diet and exercise improve insulin sensitivity and are the cornerstone of therapy, but are often difficult to maintain long term. Not surprisingly, insulin-sensitizing agents have been a focus of pharmacologic investigation in NASH. Insulin sensitizers such as the thiazolidinediones, biguanides, glucagon-like peptide-1 receptor agonists, and the dipeptidyl peptidase IV inhibitors, also known as incretins, will be discussed with respect to their mechanism of action and how these drugs might target aspects of NASH pathophysiology. Finally, we will summarize the available clinical data and review both the risks and benefits of insulin sensitizers in the treatment of NASH.
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