IOSR Journal Of Pharmacywww.iosrphr.org (e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219 Volume 7, Issue 5 Version. 1 (May 2017), PP. 01-08 1 Pioglitazone versus metformin in Egyptian non diabetic patients with Non Alcholic Fatty Liver Disease: A randomized controlled trial. Sahar K. Hgazy a , Mamdouh A. Gabr b , Nahla E. El-Ashmawy c , Maha A. Younis a * a Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Egypt b Internal Medicine Department, Faculty of Medicine, Tanta University, Egypt c Biochemistry Department, Faculty of Pharmacy, Tanta University, Egypt E-mail: mahayounis2013@yahoo.com Corresponding author* Abstract:- NAFLD is estimated to be the most common cause of chronic liver disease and there are increasing rates of NASH-related liver transplantation. This study evaluates the effect of two different insulin sensitizers, pioglitazone and metformin, on liver fat content, lipolysis and insulin sensitivity in Egyptian patients with non alcoholic fatty liver disease. Forty Egyptian patients with fatty liver were enrolled in a six-month prospective study. The patients were recruited from outpatient clinics of Department of Internal Medicine, Tanta University Hospitals with ultrasonographic diagnosis of fatty liver. The patients were randomly divided into two groups; Group I (pioglitazone group) was treated by 45 mg pioglitazone/day and Group II (metformin group) was treated by metformin 20mg/kg/day. A third group of healthy subjects served as control group. The study indicated that both antihyperglycemic drugs decreased homeostatic model assessment-insulin resistance (p<0.01), plasma free fatty acids (p<0.01) and liver fat content (p<0.01) associated with improvement of hyperechogenicity in liver ultrasound in both the pioglitazone group (p<0.001) and the metformin group (p=0.47). Both treatments also improved serum levels of alanine aminotransferase (p<0.01), aspartate aminotransferase (p<0.01), high density lipoprotein–cholesterol (p<0.01) and adiponectin (p<0.01). The insulin sensitizers pioglitazone and metformin exhibited a beneficial role in management of NAFLD. Meanwhile, pioglitazone was superior to metformin in improving liver stestosis and could provide a therapeutic option to guard against disease complications. Key words:-Egyptian; Fatty liver; insulin resistance; pioglitazone; metformin. I. INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) occurs among all ages and ethnicities and is recognized to occur in 20%– 30% of the general population [1]. NAFLD is defined as the accumulation of excessive fat in the liver without a history of excessive drinking of alcohol and any secondary cause [2]. Primary NAFLD is related to insulin resistance and strictly associated with metabolic risk factors especially obesity, diabetes and dyslipidemia [3]. NAFLD can progress slowly from simple steatosis that presents without inflammation and hepatocellular damage to non-alcoholic steatohepatitis (NASH) that demonstrates inflammation and hepatocellular damage and subsequently leads to hepatic fibrosis. NAFLD may be progressive resulting in cirrhosis and hepatocellular carcinoma [4]. Accumulation of hepatic fat is closely linked to insulin resistance, which increases lipolysis of peripheral adipose tissue resulting in increased free fatty acids influx to the liver. Moreover, insulin resistance encourages de novo triglyceride synthesis within the liver, decreased triglyceride export through very-low density lipoprotein (VLDL) and inhibits oxidation of fatty acid thereby, promoting triglyceride accumulation [5]. So, improving insulin sensitivity is one of the targets in the treatment of NAFLD. At present, insulin sensitizing drugs (like pioglitazone and metformin) have come to interest as a source to decrease insulin resistance in NAFLD patients. Pioglitazone, a thiazolidinedione derivative, is a peroxisome proliferator–activated receptor γ (PPAR-γ) agonist that improves insulin sensitivity and glucose and lipid metabolism in type II diabetes [6]. Treatment with thiazolidinediones results in consistent decrease in Free Fatty Acids (FFAs) [7], thereby decreasing FFA delivery to the liver. They also increase adiponectin levels which may help to increase lipid oxidation of fatty acids in the liver [6]. Metformin is a member of the biguanide class of drugs. It appears to improve insulin sensitivity by reducing the fat content of liver and muscle through activation of adenine monophosphate (AMP)-dependent protein kinase that results in increased mitochondrial FFA oxidation and decreased FFA and VLDL synthesis [8]. Metformin also improves sensitivity to insulin by