{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:35:47Z","timestamp":1792632947253,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pioglitazone, the only thiazolidinedione drug in clinical practice is under scrutiny due to reported adverse effects, it\u2019s unique insulin sensitising action provides rationale to remain as a therapeutic option for managing type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis comparing pioglitazone monotherapy with monotherapies of other oral antidiabetic drugs for assessing its efficacy and safety in T2DM patients. Mean changes in glycated haemoglobin (HbA1c), and mean changes in fasting blood sugar (FBS) level, body weight (BW) and homeostasis model assessment-insulin resistance (HOMA-IR) were primary and secondary outcomes, respectively. Safety outcomes were changes in lipid parameters, blood pressure and incidences of adverse events. Metafor package of R software and RevMan software based on random-effects model were used for analyses. We included 16 randomised controlled trials. Pioglitazone monotherapy showed equivalent efficacy as comparators in reducing HbA1c by 0.05% (95% CI: \u22120.21 to 0.11) and greater efficacy in reducing FBS level by 0.24\u2009mmol\/l (95% CI: \u22120.48 to \u22120.01). Pioglitazone showed similar efficacy as comparators in reducing HOMA-IR (WMD: 0.05, 95% CI: \u22120.49 to 0.59) and increasing high-density lipoprotein level (WMD: 0.02\u2009mmol\/l, 95% CI: \u22120.06 to 0.10). Improved blood pressure (WMD: \u22121.05\u2009mmHg, 95% CI: \u22124.29 to 2.19) and triglycerides level (WMD: \u22120.71\u2009mmol\/l, 95% CI: \u22121.70 to 0.28) were also observed with pioglitazone monotherapy. There was a significant association of pioglitazone with increased BW (WMD: 2.06\u2009kg, 95% CI: 1.11 to 3.01) and risk of oedema (RR: 2.21, 95% CI: 1.48 to 3.31), though the risk of hypoglycaemia was absolutely lower (RR: 0.51, 95% CI: 0.33 to 0.80). Meta-analysis supported pioglitazone as an effective treatment option for T2DM patients to ameliorate hyperglycaemia, adverse lipid metabolism and blood pressure. Pioglitazone is suggested to prescribe following individual patient\u2019s needs. It can be a choice of drug for insulin resistant T2DM patients having dyslipidaemia, hypertension or history of cardiovascular disease.<\/jats:p>","DOI":"10.1038\/s41598-019-41854-2","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T07:03:26Z","timestamp":1553843006000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Efficacy and Safety of Pioglitazone Monotherapy in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomised Controlled Trials"],"prefix":"10.1038","volume":"9","author":[{"given":"Fahmida","family":"Alam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5937-6473","authenticated-orcid":false,"given":"Md. Asiful","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafauzy","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Amjad","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Donnelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iskandar","family":"Idris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew Hua","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,29]]},"reference":[{"key":"41854_CR1","doi-asserted-by":"publisher","first-page":"562","DOI":"10.2337\/diacare.22.4.562","volume":"22","author":"SM Haffner","year":"1999","unstructured":"Haffner, S. M. et al. Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study. Diabetes Care 22, 562\u2013568 (1999).","journal-title":"Diabetes Care"},{"key":"41854_CR2","doi-asserted-by":"publisher","first-page":"S135","DOI":"10.1055\/s-2001-18576","volume":"109","author":"H Lebovitz","year":"2001","unstructured":"Lebovitz, H. Insulin resistance: definition and consequences. Exp. Clin. Endocrinol. Diabetes 109, S135\u2013S148 (2001).","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"41854_CR3","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1056\/NEJMoa072761","volume":"356","author":"SE Nissen","year":"2007","unstructured":"Nissen, S. E. & Wolski, K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356, 2457\u20132471 (2007).","journal-title":"N. Engl. J. Med."},{"key":"41854_CR4","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1016\/S0140-6736(09)60953-3","volume":"373","author":"PD Home","year":"2009","unstructured":"Home, P. D. et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 373, 2125\u20132135 (2009).","journal-title":"Lancet"},{"key":"41854_CR5","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1210\/jc.2002-021786","volume":"88","author":"I Pavo","year":"2003","unstructured":"Pavo, I. et al. Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 88, 1637\u20131645 (2003).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"41854_CR6","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1210\/er.2005-0007","volume":"27","author":"J Nigro","year":"2006","unstructured":"Nigro, J., Osman, N., Dart, A. M. & Little, P. J. Insulin resistance and atherosclerosis. Endocr. Rev. 27, 242\u2013259 (2006).","journal-title":"Endocr. Rev."},{"key":"41854_CR7","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.2337\/diacare.28.7.1547","volume":"28","author":"RB Goldberg","year":"2005","unstructured":"Goldberg, R. B. et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 28, 1547\u20131554 (2005).","journal-title":"Diabetes Care"},{"key":"41854_CR8","doi-asserted-by":"publisher","first-page":"4312","DOI":"10.1210\/jc.2004-0190","volume":"89","author":"Y Miyazaki","year":"2004","unstructured":"Miyazaki, Y. et al. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J. Clin. Endocrinol. Metab. 89, 4312\u20134319 (2004).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"41854_CR9","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1001\/jama.299.13.1561","volume":"299","author":"SE Nissen","year":"2008","unstructured":"Nissen, S. E. et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 299, 1561\u20131573 (2008).","journal-title":"JAMA"},{"key":"41854_CR10","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/j.biopha.2017.08.083","volume":"95","author":"AI Abushouk","year":"2017","unstructured":"Abushouk, A. I. et al. Peroxisome proliferator-activated receptors as therapeutic targets for heart failure. Biomed. Pharmacother. 95, 692\u2013700 (2017).","journal-title":"Biomed. Pharmacother."},{"key":"41854_CR11","doi-asserted-by":"publisher","first-page":"124","DOI":"10.2174\/187152512800388948","volume":"10","author":"A Abbas","year":"2012","unstructured":"Abbas, A., Blandon, J., Rude, J., Elfar, A. & Mukherjee, D. PPAR-\u03b3 agonist in treatment of diabetes: cardiovascular safety considerations. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents) 10, 124\u2013134 (2012).","journal-title":"Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents)"},{"key":"41854_CR12","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1592\/phco.26.10.1388","volume":"26","author":"R Jain","year":"2006","unstructured":"Jain, R. et al. Long-term Safety of Pioglitazone versus Glyburide in Patients with Recently Diagnosed Type 2 Diabetes Mellitus. Pharmacotherapy 26, 1388\u20131395 (2006).","journal-title":"Pharmacotherapy"},{"key":"41854_CR13","doi-asserted-by":"publisher","first-page":"305","DOI":"10.7326\/M15-1774","volume":"165","author":"K Cusi","year":"2016","unstructured":"Cusi, K. et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann. Intern. Med. 165, 305\u2013315 (2016).","journal-title":"Ann. Intern. Med."},{"key":"41854_CR14","doi-asserted-by":"publisher","first-page":"140","DOI":"10.2337\/dc14-2441","volume":"38","author":"SE Inzucchi","year":"2015","unstructured":"Inzucchi, S. E. et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38, 140\u2013149 (2015).","journal-title":"Diabetes Care"},{"key":"41854_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pmed.1000097","volume":"6","author":"D Moher","year":"2009","unstructured":"Moher, D., Liberati, A., Tetzlaff, J. & Altman, D. G. & PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6, 1\u20136 (2009).","journal-title":"PLoS Med."},{"key":"41854_CR16","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/S2213-8587(16)00052-8","volume":"4","author":"JH Wu","year":"2016","unstructured":"Wu, J. H. et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 4, 411\u2013419 (2016).","journal-title":"Lancet Diabetes Endocrinol"},{"key":"41854_CR17","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","volume":"343","author":"JP Higgins","year":"2011","unstructured":"Higgins, J. P. et al. The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ 343, d5928 (2011).","journal-title":"BMJ"},{"key":"41854_CR18","doi-asserted-by":"publisher","first-page":"e82880","DOI":"10.1371\/journal.pone.0082880","volume":"9","author":"GW Landman","year":"2014","unstructured":"Landman, G. W. et al. Safety and efficacy of gliclazide as treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials. PLoS ONE 9, e82880 (2014).","journal-title":"PLoS ONE"},{"key":"41854_CR19","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/S1473-3099(17)30615-1","volume":"18","author":"KZ Vardakas","year":"2018","unstructured":"Vardakas, K. Z., Voulgaris, G. L., Maliaros, A., Samonis, G. & Falagas, M. E. Prolonged versus short-term intravenous infusion of antipseudomonal \u03b2-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect. Dis. 18, 108\u2013120 (2018).","journal-title":"Lancet Infect. Dis."},{"key":"41854_CR20","unstructured":"Review manager (RevMan)[computer program] Version 5.3.5. Copenhagen: The Nordic Cochrane Centre. The Cochrane Collaboration (2014)."},{"key":"41854_CR21","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.diabres.2008.07.021","volume":"82","author":"G Erdem","year":"2008","unstructured":"Erdem, G. et al. The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus. Diabetes Res. Clin. Pract. 82, 214\u2013218 (2008).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"41854_CR22","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/jdi.12157","volume":"5","author":"A Esteghamati","year":"2014","unstructured":"Esteghamati, A., Ghasemiesfe, M., Mousavizadeh, M., Noshad, S. & Nakhjavani, M. Pioglitazone and metformin are equally effective in reduction of chemerin in patients with type 2 diabetes. J Diabetes Investig 5, 327\u2013332 (2014a).","journal-title":"J Diabetes Investig"},{"key":"41854_CR23","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1007\/s40618-014-0154-x","volume":"37","author":"A Esteghamati","year":"2014","unstructured":"Esteghamati, A. et al. Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial. J. Endocrinol. Invest. 37, 1211\u20131218 (2014b).","journal-title":"J. Endocrinol. Invest."},{"key":"41854_CR24","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.dsx.2014.09.009","volume":"9","author":"A Esteghamati","year":"2015","unstructured":"Esteghamati, A., Afarideh, M., Feyzi, S., Noshad, S. & Nakhjavani, M. Comparative effects of metformin and pioglitazone on fetuin-A and osteoprotegerin concentrations in patients with newly diagnosed diabetes: A randomized clinical trial. Diabetes Metab Syndr 9, 258\u2013265 (2015).","journal-title":"Diabetes Metab Syndr"},{"key":"41854_CR25","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/j.1365-2265.2010.03878.x","volume":"73","author":"YY Hu","year":"2010","unstructured":"Hu, Y. Y. et al. Hydrochloride pioglitazone decreases urinary cytokines excretion in type 2 diabetes. Clin. Endocrinol. (Oxf.) 73, 739\u2013743 (2010).","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"41854_CR26","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.2169\/internalmedicine.56.8096","volume":"56","author":"H Mori","year":"2017","unstructured":"Mori, H., Okada, Y. & Tanaka, Y. The Effects of Pioglitazone on Bone Formation and Resorption Markers in Type 2 Diabetes Mellitus. Intern. Med. 56, 1301\u20131306 (2017).","journal-title":"Intern. Med."},{"key":"41854_CR27","first-page":"459","volume":"52","author":"A Ramachandran","year":"2004","unstructured":"Ramachandran, A., Snehalatha, C., Salini, J. & Vijay, V. Use of glimepiride and insulin sensitizers in the treatment of type 2 diabetes\u2014a study in Indians. JAPI 52, 459 (2004).","journal-title":"JAPI"},{"key":"41854_CR28","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1111\/j.1365-2265.2007.03113.x","volume":"68","author":"MB Cooper","year":"2008","unstructured":"Cooper, M. B., Al Majali, K., Bailey, C. J. & Betteridge, D. J. Reduced postprandial proinsulinaemia and 32\u201333 split proinsulinaemia after a mixed meal in type 2 diabetic patients following sensitization to insulin with pioglitazone. Clin. Endocrinol. (Oxf.) 68, 738\u2013746 (2008).","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"41854_CR29","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2165\/00024677-200201050-00005","volume":"1","author":"B G\u00f6ke","year":"2002","unstructured":"G\u00f6ke, B. & Group, G. P. S. Improved glycemic control and lipid profile in a randomized study of pioglitazone compared with acarbose in patients with type 2 diabetes mellitus. Treat. Endocrinol. 1, 329\u2013336 (2002).","journal-title":"Treat. Endocrinol."},{"key":"41854_CR30","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.diabres.2003.09.004","volume":"63","author":"L Jovanovic","year":"2004","unstructured":"Jovanovic, L. et al. Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone. Diabetes Res. Clin. Pract. 63, 127\u2013134 (2004).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"41854_CR31","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1111\/j.1464-5491.2006.01801.x","volume":"23","author":"G Perriello","year":"2006","unstructured":"Perriello, G., Pampanelli, S., Pietro, C. & Brunetti, P. Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes. Diabet. Med. 23, 246\u2013252 (2006).","journal-title":"Diabet. Med."},{"key":"41854_CR32","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1463-1326.2006.00698.x","volume":"9","author":"J Rosenstock","year":"2007","unstructured":"Rosenstock, J. et al. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes. Diabetes Obes. Metab. 9, 175\u2013185 (2007).","journal-title":"Diabetes Obes. Metab."},{"key":"41854_CR33","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.2337\/dc10-0159","volume":"33","author":"J Rosenstock","year":"2010","unstructured":"Rosenstock, J. et al. Initial combination therapy with alogliptin and pioglitazone in drug-naive patients with type 2 diabetes. Diabetes Care 33, 2406\u20132408 (2010).","journal-title":"Diabetes Care"},{"key":"41854_CR34","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/S0149-2918(04)90068-9","volume":"26","author":"M Tan","year":"2004","unstructured":"Tan, M. et al. Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: a multicenter, randomized, double-blind, parallel-group trial. Clin. Ther. 26, 680\u2013693 (2004).","journal-title":"Clin. Ther."},{"key":"41854_CR35","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1111\/j.1742-1241.2011.02749.x","volume":"65","author":"A P\u00e9rez-Monteverde","year":"2011","unstructured":"P\u00e9rez-Monteverde, A. et al. Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-na\u00efve patients with type 2 diabetes. Int. J. Clin. Pract. 65, 930\u2013938 (2011).","journal-title":"Int. J. Clin. Pract."},{"key":"41854_CR36","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1111\/dom.12145","volume":"15","author":"M Alba","year":"2013","unstructured":"Alba, M. et al. Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function. Diabetes Obes. Metab. 15, 1101\u20131110 (2013).","journal-title":"Diabetes Obes. Metab."},{"key":"41854_CR37","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1210\/jc.2002-021786","volume":"88","author":"I Pavo","year":"2003","unstructured":"Pavo, I. et al. Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism 88, 1637\u20131645 (2003).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"41854_CR38","doi-asserted-by":"publisher","first-page":"544","DOI":"10.2337\/diacare.28.3.544","volume":"28","author":"MH Tan","year":"2005","unstructured":"Tan, M. H. et al. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care 28, 544\u2013550 (2005).","journal-title":"Diabetes Care"},{"key":"41854_CR39","doi-asserted-by":"publisher","first-page":"6068","DOI":"10.1210\/jc.2003-030861","volume":"89","author":"G Schernthaner","year":"2004","unstructured":"Schernthaner, G. et al. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J. Clin. Endocrinol. Metab. 89, 6068\u20136076 (2004).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"41854_CR40","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1111\/j.1464-5491.2005.01656.x","volume":"22","author":"T Yamanouchi","year":"2005","unstructured":"Yamanouchi, T. et al. Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes. Diabet. Med. 22, 980\u2013985 (2005).","journal-title":"Diabet. Med."},{"key":"41854_CR41","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1055\/s-0034-1370989","volume":"122","author":"C Erem","year":"2014","unstructured":"Erem, C. et al. Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Exp. Clin. Endocrinol. Diabetes 122, 295\u2013302 (2014).","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"41854_CR42","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3803\/EnM.2017.32.2.241","volume":"32","author":"NH Kim","year":"2017","unstructured":"Kim, N. H. et al. Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study. Endocrinol Metab 32, 241\u2013247 (2017).","journal-title":"Endocrinol Metab"},{"key":"41854_CR43","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1007\/s12325-013-0003-x","volume":"30","author":"S Genovese","year":"2013","unstructured":"Genovese, S. et al. Effect of pioglitazone versus metformin on cardiovascular risk markers in type 2 diabetes. Adv. Ther. 30, 190\u2013202 (2013).","journal-title":"Adv. Ther."},{"key":"41854_CR44","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/j.1464-5491.2004.01426.x","volume":"22","author":"B Charbonnel","year":"2005","unstructured":"Charbonnel, B., Matthews, D., Schernthaner, G., Hanefeld, M. & Brunetti, P. A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial. Diabet. Med. 22, 399\u2013405 (2005).","journal-title":"Diabet. Med."},{"key":"41854_CR45","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1089\/dia.2007.0248","volume":"9","author":"R Izumi","year":"2007","unstructured":"Izumi, R. et al. Clinical predictors of glycosylated hemoglobin response to thiazolidinedione therapy. Diabetes Technol. Ther. 9, 553\u2013562 (2007).","journal-title":"Diabetes Technol. Ther."},{"key":"41854_CR46","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1111\/j.1751-7176.2010.00389.x","volume":"12","author":"A Perez","year":"2010","unstructured":"Perez, A., Jacks, R., Arora, V. & Spanheimer, R. Effects of Pioglitazone and Metformin Fixed-Dose Combination Therapy on Cardiovascular Risk Markers of Inflammation and Lipid Profile Compared With Pioglitazone and Metformin Monotherapy in Patients With Type 2 Diabetes. J. Clin. Hypertens. 12, 973\u2013982 (2010).","journal-title":"J. Clin. Hypertens."},{"key":"41854_CR47","doi-asserted-by":"publisher","first-page":"625","DOI":"10.4070\/kcj.2010.40.12.625","volume":"40","author":"SH You","year":"2010","unstructured":"You, S. H., Kim, B. S., Hong, S. J., Ahn, C.-M. & Lim, D.-S. The effects of pioglitazone in reducing atherosclerosis progression and neointima volume in type 2 diabetic patients: prospective randomized study with volumetric intravascular ultrasonography analysis. Korean Circ J 40, 625\u2013631 (2010).","journal-title":"Korean Circ J"},{"key":"41854_CR48","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.amjmed.2003.09.005","volume":"115","author":"V Fonseca","year":"2003","unstructured":"Fonseca, V. Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am. J. Med. 115, 42\u201348 (2003).","journal-title":"Am. J. Med."},{"key":"41854_CR49","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/oby.2008.651","volume":"17","author":"RF Kushner","year":"2009","unstructured":"Kushner, R. F. & Sujak, M. Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone. Obesity 17, 1017\u20131022 (2009).","journal-title":"Obesity"},{"key":"41854_CR50","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1185\/030079903125002306","volume":"19","author":"S Asnani","year":"2003","unstructured":"Asnani, S., Richard, B. C., Desouza, C. & Fonseca, V. Is weight loss possible in patients treated with thiazolidinediones? Experience with a low-calorie diet. Curr. Med. Res. Opin. 19, 609\u2013613 (2003).","journal-title":"Curr. Med. Res. Opin."},{"key":"41854_CR51","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/s00125-005-0092-4","volume":"49","author":"K Al Majali","year":"2006","unstructured":"Al Majali, K. et al. The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia 49, 527\u2013537 (2006).","journal-title":"Diabetologia"},{"key":"41854_CR52","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/S0149-2918(02)85040-8","volume":"24","author":"PJ Boyle","year":"2002","unstructured":"Boyle, P. J. et al. Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records. Clin. Ther. 24, 378\u2013396 (2002).","journal-title":"Clin. Ther."},{"key":"41854_CR53","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1161\/01.CIR.0000165072.01672.21","volume":"111","author":"M Langenfeld","year":"2005","unstructured":"Langenfeld, M. et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 111, 2525\u20132531 (2005).","journal-title":"Circulation"},{"key":"41854_CR54","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1001\/jama.296.21.joc60158","volume":"296","author":"T Mazzone","year":"2006","unstructured":"Mazzone, T. et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 296, 2572\u20132581 (2006).","journal-title":"JAMA"},{"key":"41854_CR55","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1161\/CIRCULATIONAHA.107.746610","volume":"117","author":"M Davidson","year":"2008","unstructured":"Davidson, M. et al. Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation 117, 2123\u20132130 (2008).","journal-title":"Circulation"},{"key":"41854_CR56","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1056\/NEJMoa1003795","volume":"363","author":"S Zoungas","year":"2010","unstructured":"Zoungas, S. et al. Severe hypoglycemia and risks of vascular events and death. N. Engl. J. Med. 363, 1410\u20131418 (2010).","journal-title":"N. Engl. J. Med."},{"key":"41854_CR57","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1001\/jama.298.10.1180","volume":"298","author":"AM Lincoff","year":"2007","unstructured":"Lincoff, A. M., Wolski, K., Nicholls, S. J. & Nissen, S. E. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 298, 1180\u20131188 (2007).","journal-title":"JAMA"},{"key":"41854_CR58","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1111\/j.1463-1326.2007.00724.x","volume":"10","author":"E Mannucci","year":"2008","unstructured":"Mannucci, E., Monami, M., Lamanna, C., Gensini, G. & Marchionni, N. Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials. Diabetes Obes. Metab. 10, 1221\u20131238 (2008).","journal-title":"Diabetes Obes. Metab."},{"key":"41854_CR59","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1007\/s13300-017-0273-4","volume":"8","author":"E Filipova","year":"2017","unstructured":"Filipova, E., Uzunova, K., Kalinov, K. & Vekov, T. Pioglitazone and the risk of bladder cancer: a meta-analysis. Diabetes Ther 8, 705\u2013726 (2017).","journal-title":"Diabetes Ther"},{"key":"41854_CR60","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1172\/JCI31669","volume":"117","author":"PE Cryer","year":"2007","unstructured":"Cryer, P. E. Hypoglycemia, functional brain failure, and brain death. J. Clin. Invest. 117, 868\u2013870 (2007).","journal-title":"J. Clin. Invest."},{"key":"41854_CR61","doi-asserted-by":"publisher","first-page":"821","DOI":"10.14740\/jocmr3144w","volume":"9","author":"H Yanai","year":"2017","unstructured":"Yanai, H. & Adachi, H. The Low-Dose (7.5 mg\/day) Pioglitazone Therapy. J Clin Med Res 9, 821 (2017).","journal-title":"J Clin Med Res"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-41854-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-41854-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-41854-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T03:17:01Z","timestamp":1671247021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-41854-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,29]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["41854"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-41854-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,29]]},"assertion":[{"value":"8 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"5389"}}