Efficacy Study of Pioglitazone and Metformin and Association Between Pioglitazone Response and Peroxisome Proliferator-activated Receptor Gamma Gene Variants in Bangladeshi Type 2 Diabetes Mellitus Subjects

Summary

* The present study was undertaken to assess the efficacy and safety of two different insulin sensitizers (namely Pioglitazone and Metformin) among subjects with type 2 diabetes mellitus (T2DM) in Bangladesh. * A prospective, double-blind, single group, 'within-subject' designed clinical trial of 77 diagnosed T2DM patients out of 130 patients with glycosylated haemoglobin (HbA1c) ≥7.2±1.5%, aged 46±6.4 years and registered for diabetes treatment in Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM) was carried out. * The study was conducted between November 2008 and September 2010. * Baseline data, included case history of the patients,anthropometric measurement, biomedical parameters psychosocial factors, were collected from each subject and then enrolled to receive treatment with 001 drug once daily for three months, then the patients were left for wash out with metformin 850mg once daily for one month; then they received 002 drug once daily for further three months. * Dietary chart was remained as before. * DNA was isolated by Chelex method using the primers and control DNA,restriction Digestion Enzyme Endonuclease Hae 111 for genotyping PPARγ-(Peroxisome Proliferator Activated Receptor gamma)Pro12Pro * (Proline12Proline)/Pro12Ala-(Proline12 Alanine))/Ala12Ala-(Alanine12Alanine). * The blinded drugs were decoded after analyzing results, 001 tablet was pioglitazone (30 mg once daily) and 002 tablets was metformin (850mg once daily). Bio-medical outcomes were measured to assess the efficacy of both the drugs each month. After finishing the treatment period the effects of two drugs were compared using SPSS.And the association between the pioglitazone drug effects and genetic polymorphism was also assessed. * The metformin effects was assessed also using the response rate of HbA1c \<7.0% after 3 months treatment to the patients.

Timeline

Start

2008-11

Primary completion

2009-12

Completion

2010-06

Publications

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• Background Perriello G, Misericordia P, Volpi E, Santucci A, Santucci C, Ferrannini E, Ventura MM, Santeusanio F, Brunetti P, Bolli GB. Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production. Diabetes. 1994 Jul;43(7):920-8. doi: 10.2337/diab.43.7.920.
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• Background O'Moore-Sullivan TM, Prins JB. Thiazolidinediones and type 2 diabetes: new drugs for an old disease. Med J Aust. 2002 Apr 15;176(8):381-6. doi: 10.5694/j.1326-5377.2002.tb04461.x.
• Background Shihara N, Kitaoka M, Inagaki N, Kadowaki T, Koumoto S, Satoh J, Terauchi Y, Nunoi K, Yamada Y, Sakamaki H, Seino Y. Randomized controlled trial of single-agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes: A comparative study. J Diabetes Investig. 2011 Oct 7;2(5):391-8. doi: 10.1111/j.2040-1124.2011.00115.x.
• Background Kang ES, Park SY, Kim HJ, Kim CS, Ahn CW, Cha BS, Lim SK, Nam CM, Lee HC. Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes. Clin Pharmacol Ther. 2005 Aug;78(2):202-8. doi: 10.1016/j.clpt.2005.04.013.
• Background Beamer BA, Yen CJ, Andersen RE, Muller D, Elahi D, Cheskin LJ, Andres R, Roth J, Shuldiner AR. Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes. 1998 Nov;47(11):1806-8. doi: 10.2337/diabetes.47.11.1806. No abstract available.
• Background Ek J, Urhammer SA, Sorensen TI, Andersen T, Auwerx J, Pedersen O. Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men. Diabetologia. 1999 Jul;42(7):892-5. doi: 10.1007/s001250051243.
• Background Nicklas BJ, van Rossum EF, Berman DM, Ryan AS, Dennis KE, Shuldiner AR. Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene (Pro12Ala) affects metabolic responses to weight loss and subsequent weight regain. Diabetes. 2001 Sep;50(9):2172-6. doi: 10.2337/diabetes.50.9.2172.
• Background Iwata E, Matsuda H, Fukuda T, Fukuen S, Motomura T, Igarashi T, Yamamoto I, Azuma J. Mutations of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene in a Japanese population : the Pro12Ala mutation in PPAR gamma 2 is associated with lower concentrations of serum total and non-HDL cholesterol. Diabetologia. 2001 Oct;44(10):1354-5. doi: 10.1007/s001250100647. No abstract available.
• Background Oh EY, Min KM, Chung JH, Min YK, Lee MS, Kim KW, Lee MK. Significance of Pro12Ala mutation in peroxisome proliferator-activated receptor-gamma2 in Korean diabetic and obese subjects. J Clin Endocrinol Metab. 2000 May;85(5):1801-4. doi: 10.1210/jcem.85.5.6499.
• Background Snitker S, Watanabe RM, Ani I, Xiang AH, Marroquin A, Ochoa C, Goico J, Shuldiner AR, Buchanan TA; Troglitazone in Prevention of Diabetes (TRIPOD) study. Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study. Diabetes Care. 2004 Jun;27(6):1365-8. doi: 10.2337/diacare.27.6.1365.

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