A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications.
Molavi B, Rassouli N, Bagwe S, Rasouli N.
Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
Vasc Health Risk Manag. 2007;3(6):967-73. PMID: 18200815


The rising incidence of obesity and insulin resistance to epidemic proportions has closely paralleled the surge in the prevalence of diabetes and outpaced therapeutic advances in diabetes prevention and treatment. Current evidence points to obesity induced oxidative stress and chronic inflammation as the common denominators in the evolution of insulin resistance and diabetes. Of all the hypoglycemic agents in the pharmacological arsenal against diabetes, thiazolidinediones, in particular pioglitazone, as well as metformin appear to have additional effects in ameliorating oxidative stress and inflammation; rendering them attractive tools for prevention of insulin resistance and diabetes. In addition to their hypoglycemic and lipid modifying properties, pioglitazone and metformin have been shown to exert anti-oxidative and anti-inflammatory effects in vascular beds, potentially slowing the accelerated atherosclerosis in diabetes, which is the major cause of morbidity and mortality in the affected population. The combination of pioglitazone and metformin would thus appear to be an effective pharmacological intervention in prevention and treatment of diabetes. Finally, this review will address the currently available evidence on diabetic cardiomyopathy and the potential role of combination therapy with pioglitazone and metformin.


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  • Pharmacologic agents for type 2 diabetes therapy and regulation of adipogenesis. Cignarelli A, Giorgino F, Vettor R. Arch Physiol Biochem. 2013 May 31. PMID: 23724947
  • Thiazolidinediones Promote Axonal Growth through the Activation of the JNK Pathway. Quintanilla RA, Godoy JA, Alfaro I et al. PLoS One. 2013. PMID: 23741474
  • Circadian-clock system in mouse liver affected by insulin resistance. Yang SC, Tseng HL, Shieh KR. Chronobiol Int. 2013 Jun 5. PMID: 23738904
  • Clinical experience with exenatide in obese North Indian patients with type 2 diabetes mellitus. Bawa T, Dhingra V, Malhotra N et al. Indian J Endocrinol Metab. 2013 Jan. PMID: 23776858
  • Beyond glycemic control in diabetes mellitus: effects of incretin-based therapies on bone metabolism. Ceccarelli E, Guarino EG, Merlotti D et al. Front Endocrinol (Lausanne). 2013. PMID: 23785355
  • Complementing Insulin Therapy to Achieve Glycemic Control. Barnett AH. Adv Ther. 2013 Jun 25. PMID: 23797471
  • Complementing Insulin Therapy to Achieve Glycemic Control. Barnett AH. Adv Ther. 2013 Jun 25. PMID: 23797471
  • [The role of adiponectin in the pathogenesis of the metabolic syndrome and approach to therapy]. . Patol Fiziol Eksp Ter. 2013 Jan-Mar. PMID: 23805709
  • Does drug therapy reverse endothelial progenitor cell dysfunction in diabetes? Desouza CV. J Diabetes Complications. 2013 Jun 25. PMID: 23809765
  • Case-control analysis on metformin and cancer of the esophagus. Becker C, Meier CR, Jick SS et al. Cancer Causes Control. 2013 Jul 3. PMID: 23820930
  • [Diabetes and osteoporosis]. Ferrari S. Rev Med Suisse. 2013 Jun 12. PMID: 23821843
  • Function of Seipin: new insights from Bscl2/seipin knockout mouse models. Dollet L, Magré J, Cariou B et al. Biochimie. 2013 Jul 2. PMID: 23831461
  • The Influence of Diabetes in the Pathogenesis and the Clinical Course of Hepatocellular Carcinoma: Recent Findings and New Perspectives. Facciorusso A. Curr Diabetes Rev. 2013 Jun 27. PMID: 23845075
  • Thiazolidinediones and cancer: results of a meta-analysis of randomized clinical trials. Monami M, Dicembrini I, Mannucci E. Acta Diabetol. 2013 Jul 14. PMID: 23851465
  • Hippocampal calcium dysregulation at the nexus of diabetes and brain aging. Thibault O, Anderson KL, Demoll C et al. Eur J Pharmacol. 2013 Jul 17. PMID: 23872402
  • Fenofibrate suppresses melanogenesis in B16-F10 melanoma cells via activation of the p38 mitogen-activated protein kinase pathway. Huang YC, Liu KC, Chiou YL et al. Chem Biol Interact. 2013 Jul 18. PMID: 23872139
  • History of current non-insulin medications for diabetes mellitus. Quianzon CC, Cheikh IE. J Community Hosp Intern Med Perspect. 2012. PMID: 23882374
  • Comparing Pioglitazone to Insulin with Respect to Cancer, Cardiovascular and Bone Fracture Endpoints, Using Propensity Score Weights. Vallarino C, Perez A, Fusco G et al. Clin Drug Investig. 2013 Jul 24. PMID: 23881565
  • Diabetes and bone fragility: a dangerous liaison. Conti F, Wolosinska DT, Pugliese G. Aging Clin Exp Res. 2013 Aug 2. PMID: 23907773
  • Incretin-Based Therapy Compared with Non-Insulin Alternatives in Elderly Patients with Type 2 Diabetes. Zhao Q, Marcy TR. Consult Pharm. 2013 Aug 1. PMID: 23906896
  • Labisia pumila Upregulates Peroxisome Proliferator-Activated Receptor Gamma Expression in Rat Adipose Tissues and 3T3-L1 Adipocytes. Mansor F, Gu HF, Ostenson CG et al. Adv Pharmacol Sci. 2013. PMID: 23935612
  • Impact of thiazolidinediones on macular thickness and volume in diabetic eyes. Azar S, El-Mollayess GM, Al Shaar L et al. Can J Ophthalmol. 2013 Aug. PMID: 23931472
  • Nonalcoholic Fatty liver disease: diagnosis and management. Wilkins T, Tadkod A, Hepburn I et al. Am Fam Physician. 2013 Jul 1. PMID: 23939604
  • Pioglitazone does not improve insulin signaling in mice with growth hormone over-expression. Gesing A, Bartke A, Masternak M. J Endocrinol. 2013 Aug 14. PMID: 23946430
  • Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: Effects of pioglitazone and metformin treatment. Ciaraldi TP, Aroda V, Mudaliar SR et al. Metabolism. 2013 Aug 16. PMID: 23958241
  • Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: Effects of pioglitazone and metformin treatment. Ciaraldi TP, Aroda V, Mudaliar SR et al. Metabolism. 2013 Aug 16. PMID: 23958241
  • Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: Effects of pioglitazone and metformin treatment. Ciaraldi TP, Aroda V, Mudaliar SR et al. Metabolism. 2013 Aug 16. PMID: 23958241
  • Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in Sprague-Dawley rats: a novel model of endoplasmic reticulum stress. Kang SB, Kim HM, Kim HJ et al. Endocr J. 2013 Aug 20. PMID: 23965360
  • The Cardiovascular Safety of Diabetes Drugs - Insights from the Rosiglitazone Experience. Hiatt WR, Kaul S, Smith RJ. N Engl J Med. 2013 Sep 2. PMID: 23992603
  • Clinical Effect of Addition of Beraprost Sodium to Pioglitazone Treatment on the Blood Glucose Levels in Patients with Type 2 Diabetes Mellitus. Chen T, Kusunoki M, Sato D et al. Exp Clin Endocrinol Diabetes. 2013 Sep 3. PMID: 24002894
  • Insulin sensitizers in polycystic ovary syndrome. Pasquali R, Gambineri A. Front Horm Res. 2013. PMID: 24002407
  • Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome. Bajuk Studen K, Jensterle Sever M, Pfeifer M. Front Horm Res. 2013. PMID: 24002406
  • Thiazolidinediones in the Treatment of HIV/HAART-Associated Lipodystrophy Syndrome. Edgeworth A, Treacy MP, Hurst TP. AIDS Rev. 2013 Jul-Sep. PMID: 24002201
  • Increased Susceptibility of db/db Mice to Rosiglitazone-Induced Plasma Volume Expansion: Role of Dysregulation of Renal Water Transporters. Zhou L, Liu G, Jia Z et al. Am J Physiol Renal Physiol. 2013 Sep 4. PMID: 24005472
    --> -->
 
 
<type 'exceptions.AttributeError'>
Python 2.7.3: /usr/bin/python
Sun Dec 21 10:39:43 2014

A problem occurred in a Python script. Here is the sequence of function calls leading up to the error, in the order they occurred.

 /var/www-mass/thiazolidinediones.com/relatedArticles/relatedArticlesBLTC.py in ()
    360         if(debugMode): print "got keyword:",theKeyword,"<br>\n"
    361         
=>  362         returnArticles(theKeyword)
    363 elif("setupTest" in form):
    364         curPath = os.path.dirname(sys.argv[0])
returnArticles = <function returnArticles>, theKeyword = 'thiazolidinediones'
 /var/www-mass/thiazolidinediones.com/relatedArticles/relatedArticlesBLTC.py in returnArticles(keyword='thiazolidinediones')
    337         exSQL("SELECT `articles`.pmid,`articles`.title,`articles`.authors,`articles`.journal,`articles`.publishDate from `%s` LEFT JOIN `articles` ON `rel_keywords_articles`.articleID=`articles`.id WHERE `rel_keywords_articles`.keywordID=%s" % ((dbTablePrefix+"rel_keywords_articles"),keywordID))
    338         rows=curs.fetchall()
=>  339         printArticles(rows)
    340         
    341         """
global printArticles = <function printArticles>, rows = ({'authors': 'Thareja S, Aggarwal S, Bhardwaj TR, Kumar M', 'journal': 'Med Chem', 'pmid': 20218967L, 'publishDate': '2010 Mar 11', 'title': '3D-QSAR Studies on a Series of 5-Arylidine-2, 4-...elf-Organizing Molecular Field Analysis Approach.'}, {'authors': 'Berlie HD, Garwood CL', 'journal': 'Ann Pharmacother', 'pmid': 20215495L, 'publishDate': '2010 Mar 9', 'title': 'Diabetes Medications Related to an Increased Ris...nd Fall-Related Morbidity in the Elderly (April).'}, {'authors': 'Yoshizaki T, Motomura W, Tanno S, Kumei S, Yoshizaki Y, Tanno S, Okumura T', 'journal': 'J Exp Clin Cancer Res', 'pmid': 20214829L, 'publishDate': '2010 Mar 10', 'title': 'Thiazolidinediones enhance vascular endothelial ...h inhibition in non-small-cell lung cancer cells.'}, {'authors': 'Samtani MN', 'journal': 'Biopharm Drug Dispos', 'pmid': 20213855L, 'publishDate': '2010 Mar 8', 'title': 'Simple pharmacometric tools for oral anti-diabet...or oral non-insulin therapies in type 2 diabetes.'}, {'authors': 'Bruedigam C, Eijken M, Koedam M, van de Peppel J, Drabek K, Chiba H, van Leeuwen JP', 'journal': 'Stem Cells', 'pmid': 20213769L, 'publishDate': '2010 Mar 8', 'title': 'A New Concept Underlying Stem Cell Lineage Skewi...etrimental Effects of Thiazolidinediones on Bone.'}, {'authors': 'Ambrosius WT, Danis RP, Goff DC Jr, Greven CM, G...Felicetta JV, Chew EY, for the ACCORD Study Group', 'journal': 'Arch Ophthalmol', 'pmid': 20212201L, 'publishDate': '2010 Mar', 'title': 'Lack of Association Between Thiazolidinediones a...dema in Type 2 Diabetes: The ACCORD Eye Substudy.'}, {'authors': 'Reilly JB, Berns JS', 'journal': 'Semin Dial', 'pmid': 20210915L, 'publishDate': '2010 Feb 22', 'title': 'Selection and Dosing of Medications for Manageme...iabetes in Patients with Advanced Kidney Disease.'}, {'authors': 'Sim\xc3\xb3 R, Rodriguez A, Caveda E', 'journal': 'Curr Drug Saf', 'pmid': 20210732L, 'publishDate': '2010 Mar 7', 'title': 'Different Effects of Thiazolidinediones on Cardi...etes Mellitus: Pioglitazone versus Rosiglitazone.'}, {'authors': 'Antonelli A, Ferrari SM, Fallahi P, Piaggi S, Paolicchi A, Franceschini SS, Salvi M, Ferrannini E', 'journal': 'Metabolism', 'pmid': 20206950L, 'publishDate': '2010 Mar 5', 'title': 'Cytokines (interferon-gamma and tumor necrosis f...and ophthalmopathy are modulated by pioglitazone.'}, {'authors': 'Chen IC, Chao TH, Tsai WC, Li YH', 'journal': 'J Formos Med Assoc', 'pmid': 20206835L, 'publishDate': '2010 Feb', 'title': 'Rosiglitazone Reduces Plasma Levels of Inflammat... Without Diabetes Mellitus or Metabolic Syndrome.'}, {'authors': 'Thareja S, Aggarwal S, Bhardwaj TR, Kumar M', 'journal': 'Eur J Med Chem', 'pmid': 20236737L, 'publishDate': '2010 Feb 20', 'title': 'Self-organizing molecular field analysis of 2,4-...el for the development of human PTP1B inhibitors.'}, {'authors': 'Barnett AH, Cradock S, Fisher M, Hall G, Hughes E, Middleton A', 'journal': 'Int J Clin Pract', 'pmid': 20236369L, 'publishDate': '2010 Mar 5', 'title': 'Key considerations around the risks and conseque... of hypoglycaemia in people with type 2 diabetes.'}, {'authors': 'Rush WA, Crain AL, Amundson GH, Kerby TJ, Murray AD, Margolis KL', 'journal': 'Clin Med Res', 'pmid': 20305209L, 'publishDate': '2010 Mar', 'title': 'PS2-20: Racial Disparities in A1c Change and Medication Intensification.'}, {'authors': 'Mar\xc3\xadn-G\xc3\xa1mez N, Kessel-Sardi\xc3\xb1as H, Cervantes-B...z-Palmero S, Ant\xc3\xb3n-Molina F, Mart\xc3\xadnez-Garc\xc3\xada L', 'journal': 'Rev Calid Asist', 'pmid': 20304693L, 'publishDate': '2010 Mar 19', 'title': '[Biomedical research, the market, clinicians, sa...sibility post-phase III: Maintaining confidence.]'}, {'authors': 'Monte SV, Schentag JJ, Adelman MH, Paladino JA', 'journal': 'J Diabetes Sci Technol', 'pmid': 20307399L, 'publishDate': '2010 Mar 1', 'title': 'Glucose Supply and Insulin Demand Dynamics of Antidiabetic Agents.'}, {'authors': 'Ademi Z, Liew D, Hollingsworth B, Steg PG, Bhatt...CM, on behalf of the REACH Registry Investigators', 'journal': 'Am J Cardiovasc Drugs', 'pmid': 20334445L, 'publishDate': '2010 Apr 1', 'title': 'Predictors of Annual Pharmaceutical Costs in Aus...lysis of Australian Data from the REACH Registry.'}, {'authors': 'DeAngelis CD, Fontanarosa PB', 'journal': 'JAMA', 'pmid': 20332409L, 'publishDate': '2010 Mar 24', 'title': 'Ensuring integrity in industry-sponsored research: primum non nocere, revisited.'}, {'authors': 'Nissen SE', 'journal': 'JAMA', 'pmid': 20332408L, 'publishDate': '2010 Mar 24', 'title': 'Setting the RECORD Straight.'}, {'authors': 'Wang AT, McCoy CP, Murad MH, Montori VM', 'journal': 'BMJ', 'pmid': 20299696L, 'publishDate': '2010 Mar 18', 'title': 'Association between industry affiliation and pos...rosiglitazone: cross sectional systematic review.'}, {'authors': 'Defronzo RA', 'journal': 'Diabetologia', 'pmid': 20361178L, 'publishDate': '2010 Apr 2', 'title': 'Insulin resistance, lipotoxicity, type 2 diabete...e missing links. The Claude Bernard Lecture 2009.'}, ...)
 /var/www-mass/thiazolidinediones.com/relatedArticles/relatedArticlesBLTC.py in printArticles(rows=({'authors': 'Thareja S, Aggarwal S, Bhardwaj TR, Kumar M', 'journal': 'Med Chem', 'pmid': 20218967L, 'publishDate': '2010 Mar 11', 'title': '3D-QSAR Studies on a Series of 5-Arylidine-2, 4-...elf-Organizing Molecular Field Analysis Approach.'}, {'authors': 'Berlie HD, Garwood CL', 'journal': 'Ann Pharmacother', 'pmid': 20215495L, 'publishDate': '2010 Mar 9', 'title': 'Diabetes Medications Related to an Increased Ris...nd Fall-Related Morbidity in the Elderly (April).'}, {'authors': 'Yoshizaki T, Motomura W, Tanno S, Kumei S, Yoshizaki Y, Tanno S, Okumura T', 'journal': 'J Exp Clin Cancer Res', 'pmid': 20214829L, 'publishDate': '2010 Mar 10', 'title': 'Thiazolidinediones enhance vascular endothelial ...h inhibition in non-small-cell lung cancer cells.'}, {'authors': 'Samtani MN', 'journal': 'Biopharm Drug Dispos', 'pmid': 20213855L, 'publishDate': '2010 Mar 8', 'title': 'Simple pharmacometric tools for oral anti-diabet...or oral non-insulin therapies in type 2 diabetes.'}, {'authors': 'Bruedigam C, Eijken M, Koedam M, van de Peppel J, Drabek K, Chiba H, van Leeuwen JP', 'journal': 'Stem Cells', 'pmid': 20213769L, 'publishDate': '2010 Mar 8', 'title': 'A New Concept Underlying Stem Cell Lineage Skewi...etrimental Effects of Thiazolidinediones on Bone.'}, {'authors': 'Ambrosius WT, Danis RP, Goff DC Jr, Greven CM, G...Felicetta JV, Chew EY, for the ACCORD Study Group', 'journal': 'Arch Ophthalmol', 'pmid': 20212201L, 'publishDate': '2010 Mar', 'title': 'Lack of Association Between Thiazolidinediones a...dema in Type 2 Diabetes: The ACCORD Eye Substudy.'}, {'authors': 'Reilly JB, Berns JS', 'journal': 'Semin Dial', 'pmid': 20210915L, 'publishDate': '2010 Feb 22', 'title': 'Selection and Dosing of Medications for Manageme...iabetes in Patients with Advanced Kidney Disease.'}, {'authors': 'Sim\xc3\xb3 R, Rodriguez A, Caveda E', 'journal': 'Curr Drug Saf', 'pmid': 20210732L, 'publishDate': '2010 Mar 7', 'title': 'Different Effects of Thiazolidinediones on Cardi...etes Mellitus: Pioglitazone versus Rosiglitazone.'}, {'authors': 'Antonelli A, Ferrari SM, Fallahi P, Piaggi S, Paolicchi A, Franceschini SS, Salvi M, Ferrannini E', 'journal': 'Metabolism', 'pmid': 20206950L, 'publishDate': '2010 Mar 5', 'title': 'Cytokines (interferon-gamma and tumor necrosis f...and ophthalmopathy are modulated by pioglitazone.'}, {'authors': 'Chen IC, Chao TH, Tsai WC, Li YH', 'journal': 'J Formos Med Assoc', 'pmid': 20206835L, 'publishDate': '2010 Feb', 'title': 'Rosiglitazone Reduces Plasma Levels of Inflammat... Without Diabetes Mellitus or Metabolic Syndrome.'}, {'authors': 'Thareja S, Aggarwal S, Bhardwaj TR, Kumar M', 'journal': 'Eur J Med Chem', 'pmid': 20236737L, 'publishDate': '2010 Feb 20', 'title': 'Self-organizing molecular field analysis of 2,4-...el for the development of human PTP1B inhibitors.'}, {'authors': 'Barnett AH, Cradock S, Fisher M, Hall G, Hughes E, Middleton A', 'journal': 'Int J Clin Pract', 'pmid': 20236369L, 'publishDate': '2010 Mar 5', 'title': 'Key considerations around the risks and conseque... of hypoglycaemia in people with type 2 diabetes.'}, {'authors': 'Rush WA, Crain AL, Amundson GH, Kerby TJ, Murray AD, Margolis KL', 'journal': 'Clin Med Res', 'pmid': 20305209L, 'publishDate': '2010 Mar', 'title': 'PS2-20: Racial Disparities in A1c Change and Medication Intensification.'}, {'authors': 'Mar\xc3\xadn-G\xc3\xa1mez N, Kessel-Sardi\xc3\xb1as H, Cervantes-B...z-Palmero S, Ant\xc3\xb3n-Molina F, Mart\xc3\xadnez-Garc\xc3\xada L', 'journal': 'Rev Calid Asist', 'pmid': 20304693L, 'publishDate': '2010 Mar 19', 'title': '[Biomedical research, the market, clinicians, sa...sibility post-phase III: Maintaining confidence.]'}, {'authors': 'Monte SV, Schentag JJ, Adelman MH, Paladino JA', 'journal': 'J Diabetes Sci Technol', 'pmid': 20307399L, 'publishDate': '2010 Mar 1', 'title': 'Glucose Supply and Insulin Demand Dynamics of Antidiabetic Agents.'}, {'authors': 'Ademi Z, Liew D, Hollingsworth B, Steg PG, Bhatt...CM, on behalf of the REACH Registry Investigators', 'journal': 'Am J Cardiovasc Drugs', 'pmid': 20334445L, 'publishDate': '2010 Apr 1', 'title': 'Predictors of Annual Pharmaceutical Costs in Aus...lysis of Australian Data from the REACH Registry.'}, {'authors': 'DeAngelis CD, Fontanarosa PB', 'journal': 'JAMA', 'pmid': 20332409L, 'publishDate': '2010 Mar 24', 'title': 'Ensuring integrity in industry-sponsored research: primum non nocere, revisited.'}, {'authors': 'Nissen SE', 'journal': 'JAMA', 'pmid': 20332408L, 'publishDate': '2010 Mar 24', 'title': 'Setting the RECORD Straight.'}, {'authors': 'Wang AT, McCoy CP, Murad MH, Montori VM', 'journal': 'BMJ', 'pmid': 20299696L, 'publishDate': '2010 Mar 18', 'title': 'Association between industry affiliation and pos...rosiglitazone: cross sectional systematic review.'}, {'authors': 'Defronzo RA', 'journal': 'Diabetologia', 'pmid': 20361178L, 'publishDate': '2010 Apr 2', 'title': 'Insulin resistance, lipotoxicity, type 2 diabete...e missing links. The Claude Bernard Lecture 2009.'}, ...))
    315                 pmURL="http://www.ncbi.nlm.nih.gov/pubmed/"+str(row['pmid'])
    316                 if(truncateAuthors):
=>  317                         authorsSplit=row['authors'].split(', ')
    318                         if(len(authorsSplit)>3):
    319                                 authorsString=""
authorsSplit = ['Zhou L', 'Liu G', 'Jia Z', 'Yang KT', 'Sun Y', 'Kakizoe Y', 'Liu M', 'Zhou SF', 'Chen R', 'Yang B', 'Yang T'], row = {'authors': None, 'journal': None, 'pmid': None, 'publishDate': None, 'title': None}, ].split undefined

<type 'exceptions.AttributeError'>: 'NoneType' object has no attribute 'split'
      args = ("'NoneType' object has no attribute 'split'",)
      message = "'NoneType' object has no attribute 'split'"