Effect of pioglitazone on nonalcoholic fatty liver disease in morbid obese patients; a randomized controlled trial


1 Department of General Surgery, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran

3 Isfahan Endocrine and Metabolism-Research Center, Isfahan University of Medical Science, Isfahan, Iran

4 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Nonalcoholic fatty liver disease (NAFLD) is a common obesity-related disease. In this study, we aimed to investigate the effects of pioglitazone on NAFLD in morbid obese patients.
Materials and Methods: This is a randomized controlled trial study that was performed in 2020–2021 on 44 patients who had grade 3 NAFLD. At the beginning of the study, we collected the following data: age, gender, body mass index (BMI), fasting blood glucose (FBS), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), and the total size and volume of the liver and the left lobe of the liver. Patients in the control group were given a special diet. For patients in the treatment group, pioglitazone 15 mg tablets were administered twice daily for 4 months.
Results: At the beginning of the study, all patients in both groups had grade 3 of NAFLD. After the treatments, 50% of the pioglitazone group had grade 1 NAFLD, and 50% of other patients had grade 2 that showed significant improvements in patients (P < 0.001). We also found significant improvements in the following items in the intervention group: liver size (P < 0.001), size of the left liver lobe (P < 0.001), FBS (P = 0.036), ALT (P = 0.011), and BMI (P < 0.001). No significant improvements were found in the control group (P > 0.05).
Conclusion: The use of pioglitazone for 4 months resulted in improvements in fatty liver stage, liver size, BMI, FBS, and lipid profile. These data show the effectiveness of pioglitazone in NAFLD.


Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018;24:908-22.  Back to cited text no. 1
Rinella ME, Sanyal AJ. Management of NAFLD: A stage-based approach. Nat Rev Gastroenterol Hepatol 2016;13:196-205.  Back to cited text no. 2
Puigvehí M, Hashim D, Haber PK, Dinani A, Schiano TD, Asgharpour A, et al. Liver transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades. Am J Transplant 2020;20:220-30.  Back to cited text no. 3
Haddad S, Ghadimi K, Abrishamkar R, Asl NS. Comparing laparoscopy and laparotomy procedures in the radical hysterectomy surgery for endometrial cancer: A basic review. Am J Transl Res 2021;13:2456-61.  Back to cited text no. 4
Gadiparthi C, Spatz M, Greenberg S, Iqbal U, Kanna S, Satapathy SK, et al. NAFLD epidemiology, emerging pharmacotherapy, liver transplantation implications and the trends in the United States. J Clin Transl Hepatol 2020;8:215-21.  Back to cited text no. 5
Rogha M, Abtahi H, Asadpour L, Ghazavi H, Pourmohammadi R, Maleki M, et al. Therapeutic effect of intratympanic injection of dexamethasone plus hyaluronic acid on patients with Meniere's disease. Iran J Otorhinolaryngol 2019;31:217-23.  Back to cited text no. 6
Xian YX, Weng JP, Xu F. MAFLD vs. NAFLD: Shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy. Chin Med J (Engl) 2020;134:8-19.  Back to cited text no. 7
Lazo M, Bilal U, Perez-Escamilla R. Epidemiology of NAFLD and type 2 diabetes: Health disparities among persons of Hispanic origin. Curr Diab Rep 2015;15:116.  Back to cited text no. 8
Moradi Farsani D, Ghadimi K, Abrishamkar R, Montazeri K, Peyman A. Evaluating sedative effects of dexmedetomidine and morphine in the patients with opioid use disorder undergoing cataract surgery. Am J Clin Exp Immunol 2021;10:30-6.  Back to cited text no. 9
Lu FB, Hu ED, Xu LM, Chen L, Wu JL, Li H, et al. The relationship between obesity and the severity of non-alcoholic fatty liver disease: Systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2018;12:491-502.  Back to cited text no. 10
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. Obes Facts 2016;9:65-90.  Back to cited text no. 11
Alavi A, Izadpanahi MH, Haghshenas L, Faridizad R, Eslami MJ, Ghadimi K. Comparing urine levels of BLCA-4 nuclear matrix protein in patients with bladder cancer and non-bladder cancer. Int J Physiol Pathophysiol Pharmacol 2019;11:289-92.  Back to cited text no. 12
Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol 2017;67:829-46.  Back to cited text no. 13
Al-Majed A, Bakheit AH, Abdel Aziz HA, Alharbi H, Al-Jenoobi FI. Pioglitazone. Profiles Drug Subst Excip Relat Methodol 2016;41:379-438.  Back to cited text no. 14
Ali Kiaei B, Moradi Farsani D, Ghadimi K, Shahali M. Evaluation of the relationship between serum sodium concentration and mortality rate in ICU patients with traumatic brain injury. Arch Neurosci 2018;5.  Back to cited text no. 15
Selby LV, Ejaz A, Brethauer SA, Pawlik TM. Fatty liver disease and primary liver cancer: Disease mechanisms, emerging therapies and the role of bariatric surgery. Expert Opin Investig Drugs 2020;29:107-10.  Back to cited text no. 16
Fahim M, Rafiee Zadeh A, Shoureshi P, Ghadimi K, Cheshmavar M, Sheikhinia N, et al. Alcohol and multiple sclerosis: An immune system-based review. Int J Physiol Pathophysiol Pharmacol 2020;12:58-69.  Back to cited text no. 17
Lee DH. Imaging evaluation of non-alcoholic fatty liver disease: Focused on quantification. Clin Mol Hepatol 2017;23:290-301.  Back to cited text no. 18
Lian J, Fu J. Pioglitazone for NAFLD patients with prediabetes or type 2 diabetes mellitus: A meta-analysis. Front Endocrinol (Lausanne) 2021;12:615409.  Back to cited text no. 19
Ito D, Shimizu S, Inoue K, Saito D, Yanagisawa M, Inukai K, et al. Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: A randomized, 24-week, open-label, active-controlled trial. Diabetes Care 2017;40:1364-72.  Back to cited text no. 20