pioglitazone and Myocardial Infarction studies

Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.
pioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity.

Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).

Research Excerpts

Excerpt	Relevance	Reference
"Pioglitazone may be effective for secondary prevention in patients with stroke/transient ischemic attack and with prediabetes, particularly in those with good adherence."	9.30	Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial. ( Dearborn-Tomazos, J; Ford, GA; Furie, KL; Gorman, M; Inzucchi, SE; Kernan, WN; Lovejoy, AM; Spence, JD; Viscoli, CM; Young, LH, 2019)
"After an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or MI derive a greater absolute benefit from pioglitazone compared with patients at lower risk."	9.24	Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. ( Conwit, R; Dearborn, JL; Fayad, P; Furie, KL; Gorman, M; Guarino, PD; Inzucchi, SE; Kent, DM; Kernan, WN; Stuart, A; Viscoli, CM; Young, LH, 2017)
"Efficacy [myocardial infarction (MI) or recurrent stroke] new-onset diabetes) and adverse outcomes (oedema, weight gain, heart failure and bone fracture) were examined for subjects assigned to pioglitazone or placebo within strata defined by mode dose of study drug taken (i."	9.22	Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. ( Abdul-Ghani, M; Dandona, P; DeFronzo, R; Furie, K; Inzucchi, SE; Kernan, WN; Spence, JD; Viscoli, C; Young, LH, 2022)
"In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo."	9.22	Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. ( Adams, HP; Berger, L; Brass, LM; Carolei, A; Clark, W; Conwit, R; Coull, B; Ford, GA; Furie, KL; Gorman, M; Guarino, PD; Inzucchi, SE; Kernan, WN; Kleindorfer, D; Lovejoy, AM; O'Leary, JR; Parsons, MW; Peduzzi, PN; Ringleb, P; Schwartz, GG; Sen, S; Spence, JD; Tanne, D; Viscoli, CM; Wang, D; Winder, TR; Young, LH, 2016)
"Among patients with insulin resistance but without diabetes who had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events."	9.22	Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. ( Dagogo-Jack, S; Furie, KL; Gorman, M; Inzucchi, SE; Ismail-Beigi, F; Kernan, WN; Korytkowski, MT; Lovejoy, AM; Pratley, RE; Schwartz, GG; Viscoli, CM; Young, LH, 2016)
" Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, nondiabetic patients with a recent ischemic stroke or TIA."	9.19	Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. ( Brass, LM; Carolei, A; Conwit, R; Ford, GA; Furie, KL; Gorman, M; Guarino, PD; Inzucchi, SE; Kernan, WN; Lovejoy, AM; Parsons, MW; Peduzzi, PN; Ringleb, PA; Schwartz, GG; Spence, JD; Tanne, D; Viscoli, CM; Young, LH, 2014)
"Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM)."	9.16	Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus. ( Iwasaka, T; Miyasaka, Y; Murakawa, K; Sugiura, T; Tsujimoto, S; Yokoe, H; Yoshida, S; Yuasa, F; Yuyama, R, 2012)
"To examine the safety and efficacy of pioglitazone in patients with ST elevation myocardial infarction (STEMI) treated with primary BMS implantation."	9.14	Efficacy and safety of pioglitazone in patients with ST elevation myocardial infarction treated with primary stent implantation. ( Domae, H; Kaneda, H; Matsumi, J; Minami, Y; Miyashita, Y; Mizuno, S; Saito, S; Shiono, T; Sugitatsu, K; Takahashi, S; Taketani, Y, 2009)
"This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI)."	9.12	The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study. ( Charbonnel, B; Dormandy, JA; Erdmann, E; Massi-Benedetti, M; Moules, IK; Skene, AM, 2007)
"Although the incidence of serious heart failure was increased with pioglitazone versus placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in patients with serious heart failure."	9.12	Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). ( Charbonnel, B; Dormandy, JA; Erdmann, E; Massi-Benedetti, M; Skene, AM; Spanheimer, R; Standl, E; Tan, M; Wilcox, RG; Yates, J, 2007)
" This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery."	7.83	Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis. ( Farag, NE; Khodeer, DM; Moustafa, YM; Zaitone, SA, 2016)
"Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference."	7.76	Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. ( Ali, F; Graham, DJ; Kelman, JA; MaCurdy, TE; Ouellet-Hellstrom, R; Sholley, C; Worrall, C, 2010)
"The insulin-sensitizing drug pioglitazone has been reported to be protective against myocardial infarction."	7.75	Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction. ( Fujiwara, H; Fujiwara, T; Iwasa, M; Kawamura, I; Kobayashi, H; Minatoguchi, S; Nagashima, K; Narentuoya, B; Nishigaki, K; Sumi, S; Takemura, G; Ushikoshi, H; Yamaki, T; Yasuda, S, 2009)
"Rosiglitazone was found associated with approximately a 43% increase in risk of acute myocardial infarction (AMI) in a two meta-analyses of clinical trials."	7.75	Rosiglitazone and myocardial infarction in patients previously prescribed metformin. ( Bassett, K; Carney, G; Dormuth, CR; Maclure, M; Schneeweiss, S; Wright, JM, 2009)
" This study aimed to investigate the efficacy and safety of low-dose pioglitazone (15 mg per day) in patients with acute myocardial infarction (AMI) and type 2 DM or impaired glucose tolerance (IGT) treated with coronary angioplasty using bare metal stent (BMS)."	7.74	Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty with the use of bare metal stent in patients with acute myocardial infarction and with type 2 diabetes mellitus or impaired glucose tolerance. ( Echizen, T; Hanada, H; Higuma, T; Horiuchi, D; Katoh, C; Okumura, K; Osanai, T; Sasaki, S; Sutoh, N; Yokota, T; Yokoyama, J, 2007)
" Because proinflammatory cytokines play a critical role in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of pioglitazone treatment in an experimental model of chronic heart failure."	7.71	Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction. ( Egashira, K; Hayashidani, S; Ikeuchi, M; Ishibashi, M; Kubota, T; Shiomi, T; Suematsu, N; Takeshita, A; Tsutsui, H; Wen, J, 2002)
"Pioglitazone (PIO) is a new class of anti-diabetic agent with an anti-inflammatory effect."	6.76	Effect of pretreatment with pioglitazone on reperfusion injury in diabetic patients with acute myocardial infarction. ( Abe, M; Kasahara, Y; Kataoka, Y; Kokubu, N; Otsuka, Y; Yagi, N, 2011)
" IRIS was a randomized, placebo controlled, double-blind trial testing pioglitazone to prevent stroke or myocardial infarction in patients with a recent ischemic stroke or transient ischemic attack."	5.34	Adherence to study drug in a stroke prevention trial"?>. ( Furie, KL; Gorman, M; Kernan, WN; Kiran, A; Viscoli, CM, 2020)
"Pioglitazone may be effective for secondary prevention in patients with stroke/transient ischemic attack and with prediabetes, particularly in those with good adherence."	5.30	Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial. ( Dearborn-Tomazos, J; Ford, GA; Furie, KL; Gorman, M; Inzucchi, SE; Kernan, WN; Lovejoy, AM; Spence, JD; Viscoli, CM; Young, LH, 2019)
"After an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or MI derive a greater absolute benefit from pioglitazone compared with patients at lower risk."	5.24	Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. ( Conwit, R; Dearborn, JL; Fayad, P; Furie, KL; Gorman, M; Guarino, PD; Inzucchi, SE; Kent, DM; Kernan, WN; Stuart, A; Viscoli, CM; Young, LH, 2017)
"Efficacy [myocardial infarction (MI) or recurrent stroke] new-onset diabetes) and adverse outcomes (oedema, weight gain, heart failure and bone fracture) were examined for subjects assigned to pioglitazone or placebo within strata defined by mode dose of study drug taken (i."	5.22	Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. ( Abdul-Ghani, M; Dandona, P; DeFronzo, R; Furie, K; Inzucchi, SE; Kernan, WN; Spence, JD; Viscoli, C; Young, LH, 2022)
"In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo."	5.22	Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. ( Adams, HP; Berger, L; Brass, LM; Carolei, A; Clark, W; Conwit, R; Coull, B; Ford, GA; Furie, KL; Gorman, M; Guarino, PD; Inzucchi, SE; Kernan, WN; Kleindorfer, D; Lovejoy, AM; O'Leary, JR; Parsons, MW; Peduzzi, PN; Ringleb, P; Schwartz, GG; Sen, S; Spence, JD; Tanne, D; Viscoli, CM; Wang, D; Winder, TR; Young, LH, 2016)
"Among patients with insulin resistance but without diabetes who had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events."	5.22	Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. ( Dagogo-Jack, S; Furie, KL; Gorman, M; Inzucchi, SE; Ismail-Beigi, F; Kernan, WN; Korytkowski, MT; Lovejoy, AM; Pratley, RE; Schwartz, GG; Viscoli, CM; Young, LH, 2016)
" Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, nondiabetic patients with a recent ischemic stroke or TIA."	5.19	Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. ( Brass, LM; Carolei, A; Conwit, R; Ford, GA; Furie, KL; Gorman, M; Guarino, PD; Inzucchi, SE; Kernan, WN; Lovejoy, AM; Parsons, MW; Peduzzi, PN; Ringleb, PA; Schwartz, GG; Spence, JD; Tanne, D; Viscoli, CM; Young, LH, 2014)
"To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes (hospitalisation, myocardial infarction and stroke) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality."	5.16	Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study population. ( Anker, SD; Cairns, R; Clark, AL; Doehner, W; Dormandy, JA; Erdmann, E; Ferrannini, E, 2012)
"Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM)."	5.16	Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus. ( Iwasaka, T; Miyasaka, Y; Murakawa, K; Sugiura, T; Tsujimoto, S; Yokoe, H; Yoshida, S; Yuasa, F; Yuyama, R, 2012)
"To examine the safety and efficacy of pioglitazone in patients with ST elevation myocardial infarction (STEMI) treated with primary BMS implantation."	5.14	Efficacy and safety of pioglitazone in patients with ST elevation myocardial infarction treated with primary stent implantation. ( Domae, H; Kaneda, H; Matsumi, J; Minami, Y; Miyashita, Y; Mizuno, S; Saito, S; Shiono, T; Sugitatsu, K; Takahashi, S; Taketani, Y, 2009)
" This analysis from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) evaluated the effects of pioglitazone on the prespecified MACE end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE1) and on 6 post hoc MACE composites (various combinations of all-cause, cardiovascular, or cardiac mortality; plus nonfatal myocardial infarction; plus nonfatal stroke; and/or acute coronary syndrome) in patients with type 2 diabetes."	5.13	Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10). ( Erdmann, E; Kupfer, S; Wilcox, R, 2008)
"This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI)."	5.12	The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study. ( Charbonnel, B; Dormandy, JA; Erdmann, E; Massi-Benedetti, M; Moules, IK; Skene, AM, 2007)
"Although the incidence of serious heart failure was increased with pioglitazone versus placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in patients with serious heart failure."	5.12	Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). ( Charbonnel, B; Dormandy, JA; Erdmann, E; Massi-Benedetti, M; Skene, AM; Spanheimer, R; Standl, E; Tan, M; Wilcox, RG; Yates, J, 2007)
"Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events."	5.11	Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. ( Betteridge, J; Birkeland, K; Charbonnel, B; Dormandy, JA; Eckland, DJ; Erdmann, E; Golay, A; Heine, RJ; Korányi, L; Laakso, M; Lefèbvre, PJ; Massi-Benedetti, M; Mokán, M; Moules, IK; Murray, GD; Norkus, A; Pirags, V; Podar, T; Scheen, A; Scherbaum, W; Schernthaner, G; Schmitz, O; Skene, AM; Skrha, J; Smith, U; Standl, E; Tan, MH; Taton, J; Wilcox, RG; Wilhelmsen, L, 2005)
" Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n = 15 studies; odds ratio 1."	4.87	Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies. ( Kwok, CS; Loke, YK; Singh, S, 2011)
"A meta-analysis of 42 clinical trials suggested that rosiglitazone, a widely used thiazolidinedione, was associated with a 43% greater risk of myocardial infarction (P = 0."	4.84	Rosiglitazone and cardiovascular risk. ( Diamond, GA; Kaul, S, 2008)
" Pioglitazone use was determined in 6-month study intervals, with outcome events of myocardial infarction (MI), ischemic stroke, and heart failure."	3.91	Detecting pioglitazone use and risk of cardiovascular events using electronic health record data in a large cohort of Chinese patients with type 2 diabetes. ( Dong, X; Du, X; Jing, S; Liu, Y; Miao, S; Wang, L; Xu, H; Xu, T; Zhang, X, 2019)
"To describe trends over time in the initiation of rosiglitazone and pioglitazone-both in the thiazolidinedione (TZD) class-and medications from the dipeptidyl peptidase-4 (DPP-4) inhibitor class before and after the FDA removed a black box warning and restricted access program for rosiglitazone regarding an increased risk of myocardial infarction."	3.91	Implications of Removing Rosiglitazone's Black Box Warning and Restricted Access Program on the Uptake of Thiazolidinediones and Dipeptidyl Peptidase-4 Inhibitors Among Patients with Type 2 Diabetes. ( Cole, AL; Dusetzina, SB; Hickson, RP, 2019)
" This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery."	3.83	Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis. ( Farag, NE; Khodeer, DM; Moustafa, YM; Zaitone, SA, 2016)
"Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without."	3.82	PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study. ( Charbonnel, B; Dormandy, J; Erdmann, E; Massi-Benedetti, M; Wilcox, R, 2007)
" Treatment with pioglitazone improved heart function by decreasing the expression of AGEs and OX-62 in the rats with myocardial infarction (MI) plus diabetes."	3.80	Advanced glycation end products promote heart failure through inducing the immune maturation of dendritic cells. ( Cao, W; Chen, J; Chen, X; Chen, Y; Liu, P, 2014)
"Examine feasibility of a new strategy to perform Electronic Medical Record database valid Comparative Effectiveness Research (CER), using determination of whether rosiglitazone (ROS) treatment increases Acute myocardial infarction (MI) in comparison to pioglitazone (PIO) as a model question."	3.79	A new "Comparative Effectiveness" assessment strategy using the THIN database: comparison of the cardiac complications of pioglitazone and rosiglitazone. ( Tannen, R; Wang, X; Weiner, MG; Xie, D; Yu, M, 2013)
"Compared with insulin, pioglitazone was associated with a significant reduction in the risk of MI and stroke requiring hospitalization, and a significant reduction in the risk of other selected cancers."	3.79	Comparing pioglitazone to insulin with respect to cancer, cardiovascular and bone fracture endpoints, using propensity score weights. ( Bron, M; Fusco, G; Joseph, G; Liang, H; Manne, S; Perez, A; Vallarino, C; Yu, S, 2013)
"The aim of this study was to conduct a direct comparison of TZDs (pioglitazone and rosiglitazone) and their relationship to cardiovascular events (myocardial infarction [MI], angina, congestive heart failure [CHF], and cerebral vascular accident [CVA]) in Taiwanese patients with type 2 diabetes mellitus (DM)."	3.77	Incidence of cardiovascular events in which 2 thiazolidinediones are used as add-on treatments for type 2 diabetes mellitus in a Taiwanese population. ( Chang, YW; Chen, WL; Chou, CC; Kao, TW; Loh, CH; Wang, CC, 2011)
"Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference."	3.76	Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. ( Ali, F; Graham, DJ; Kelman, JA; MaCurdy, TE; Ouellet-Hellstrom, R; Sholley, C; Worrall, C, 2010)
"This study directly compares risk of acute myocardial infarction (AMI), acute heart failure (AHF), or all-cause death among pioglitazone- and rosiglitazone-treated patients in a managed-care population."	3.76	Risk of cardiovascular events and all-cause mortality in patients treated with thiazolidinediones in a managed-care population. ( Bohn, RL; Chang, CL; Cziraky, MJ; Sarawate, CA; Wertz, DA; Willey, VJ, 2010)
"Among older patients with diabetes, pioglitazone is associated with a significantly lower risk of heart failure and death than is rosiglitazone."	3.75	Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. ( Austin, PC; Gomes, T; Hux, JE; Juurlink, DN; Lipscombe, LL; Mamdani, MM, 2009)
"Rosiglitazone was found associated with approximately a 43% increase in risk of acute myocardial infarction (AMI) in a two meta-analyses of clinical trials."	3.75	Rosiglitazone and myocardial infarction in patients previously prescribed metformin. ( Bassett, K; Carney, G; Dormuth, CR; Maclure, M; Schneeweiss, S; Wright, JM, 2009)
"To determine if an association exists between thiazolidinedione (rosiglitazone or pioglitazone) exposure and acute myocardial infarction, and if the timing of drug initiation relative to the onset of myocardial infarction affected the frequency of the event."	3.75	Association between extent of thiazolidinedione exposure and risk of acute myocardial infarction. ( Dore, DD; Lapane, KL; Mor, V; Trivedi, AN, 2009)
"The insulin-sensitizing drug pioglitazone has been reported to be protective against myocardial infarction."	3.75	Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction. ( Fujiwara, H; Fujiwara, T; Iwasa, M; Kawamura, I; Kobayashi, H; Minatoguchi, S; Nagashima, K; Narentuoya, B; Nishigaki, K; Sumi, S; Takemura, G; Ushikoshi, H; Yamaki, T; Yasuda, S, 2009)
" This study aimed to investigate the efficacy and safety of low-dose pioglitazone (15 mg per day) in patients with acute myocardial infarction (AMI) and type 2 DM or impaired glucose tolerance (IGT) treated with coronary angioplasty using bare metal stent (BMS)."	3.74	Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty with the use of bare metal stent in patients with acute myocardial infarction and with type 2 diabetes mellitus or impaired glucose tolerance. ( Echizen, T; Hanada, H; Higuma, T; Horiuchi, D; Katoh, C; Okumura, K; Osanai, T; Sasaki, S; Sutoh, N; Yokota, T; Yokoyama, J, 2007)
"Our findings from a large population-based cohort of US seniors are compatible with an increased risk of all-cause mortality and congestive heart failure in patients initiating therapy with rosiglitazone compared with similar patients initiating therapy with pioglitazone."	3.74	Comparison of cardiovascular outcomes in elderly patients with diabetes who initiated rosiglitazone vs pioglitazone therapy. ( Levin, R; Setoguchi, S; Solomon, DH; Winkelmayer, WC, 2008)
"In this population-based study of older patients with diabetes, TZD treatment, primarily with rosiglitazone, was associated with an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments."	3.74	Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. ( Alter, DA; Gomes, T; Hux, JE; Juurlink, DN; Lévesque, LE; Lipscombe, LL, 2007)
"To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas."	3.74	Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000-2007. ( Koro, CE; Landon, J; Walker, AM, 2008)
" Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice."	3.72	Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction. ( Bauersachs, J; Bayer, B; Ertl, G; Frantz, S; Galuppo, P; Hu, K; Schmidt, I; Strotmann, J; Widder, J; Witzel, CC, 2004)
" Because proinflammatory cytokines play a critical role in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of pioglitazone treatment in an experimental model of chronic heart failure."	3.71	Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction. ( Egashira, K; Hayashidani, S; Ikeuchi, M; Ishibashi, M; Kubota, T; Shiomi, T; Suematsu, N; Takeshita, A; Tsutsui, H; Wen, J, 2002)
"Pioglitazone (PIO) is a new class of anti-diabetic agent with an anti-inflammatory effect."	2.76	Effect of pretreatment with pioglitazone on reperfusion injury in diabetic patients with acute myocardial infarction. ( Abe, M; Kasahara, Y; Kataoka, Y; Kokubu, N; Otsuka, Y; Yagi, N, 2011)
"The incidence of congestive cardiac failure was similar with pioglitazone (12/1857) and non-pioglitazone (10/1856) treatments."	2.42	Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide. ( Belcher, G; Edwards, G; Goh, KL; Lambert, C; Valbuena, M, 2004)
"Pioglitazone (3 mg/kg/day) was given to the combined therapy and pioglitazone groups by oral gavage at the same time for another 2 weeks."	1.42	Peroxisome Proliferator-Activated Receptor Gamma Promotes Mesenchymal Stem Cells to Express Connexin43 via the Inhibition of TGF-β1/Smads Signaling in a Rat Model of Myocardial Infarction. ( Guo, T; Hou, J; Huang, H; Long, H; Wang, J; Wang, L; Wang, T; Wu, Q; Xing, Y; Zheng, S; Zhong, T; Zhou, C, 2015)
": The aim of the study was to verify if the analysis of a large spontaneous reporting database could generate early signals on these adverse drug reactions (ADRs) associated with TZDs."	1.38	Cardiovascular, ocular and bone adverse reactions associated with thiazolidinediones: a disproportionality analysis of the US FDA adverse event reporting system database. ( Biagi, C; Marchesini, G; Marra, A; Motola, D; Piccinni, C; Poluzzi, E; Raschi, E, 2012)
"Telmisartan is an angiotensin II receptor blocker, which acts as a partial agonist of peroxisome proliferator activator receptor-γ (PPAR-γ)."	1.38	Different roles of PPAR-γ activity on physiological and pathological alteration after myocardial ischemia. ( Hirata, Y; Hishikari, K; Isobe, M; Masumura, M; Nagai, R; Nagashima, A; Ogawa, M; Shimizu, T; Suzuki, J; Takayama, K; Watanabe, R, 2012)
"The frequency of edema and cardiac failure was significantly higher with TZDs than in other patients (18% and 7."	1.37	Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database. ( Berthet, S; Lapeyre-Mestre, M; Montastruc, JL; Olivier, P, 2011)
"Pretreatment with pioglitazone significantly increased the CTE in vitro (1."	1.37	Pretreatment of human mesenchymal stem cells with pioglitazone improved efficiency of cardiomyogenic transdifferentiation and cardiac function. ( Hida, N; Miyoshi, S; Nishiyama, N; Ogawa, S; Segawa, K; Shinmura, D; Togashi, I; Tsuji, H; Tsukada, Y; Tsuruta, H; Umezawa, A, 2011)
"Pioglitazone was associated with reduced all cause mortality compared with metformin."	1.35	Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. ( Curcin, V; Elliott, P; Hughes, RI; Khunti, K; Little, MP; Majeed, A; Millett, CJ; Molokhia, M; Ng, A; Tzoulaki, I; Wilkins, MR, 2009)
"Pioglitazone did inhibit the increase in expressions vs I/R (P < 0."	1.35	Antiapoptosis and mitochondrial effect of pioglitazone preconditioning in the ischemic/reperfused heart of rat. ( Feng, YB; Lang, MJ; Li, J; Mao, XB; Tian, L, 2008)
"The use of PPAR-gamma agonists in the treatment of heart failure is, however, controversial."	1.32	Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure. ( Thiemermann, C, 2004)

Research

Studies (95)

Authors

Clinical Trials (9)

Trial Overview

Trial Outcomes

Acute Coronary Syndrome

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	48 (50.53)	29.6817
2010's	44 (46.32)	24.3611
2020's	3 (3.16)	2.80

Authors	Studies
Spence, JD	4
Viscoli, C	1
Kernan, WN	7
Young, LH	6
Furie, K	1
DeFronzo, R	1
Abdul-Ghani, M	1
Dandona, P	1
Inzucchi, SE	7
Konegawa, Y	1
Kuwahara, T	1
Jo, JI	1
Murata, K	1
Takeda, T	1
Ikeda, T	1
Minatoya, K	1
Masumoto, H	1
Tabata, Y	1
Kiran, A	1
Viscoli, CM	6
Furie, KL	7
Gorman, M	6
Hankey, GJ	1
Dearborn, JL	1
Kent, DM	1
Conwit, R	3
Fayad, P	1
Guarino, PD	3
Stuart, A	1
Toh, S	1
Reichman, ME	1
Graham, DJ	2
Hampp, C	1
Zhang, R	1
Butler, MG	1
Iyer, A	1
Rucker, M	1
Pimentel, M	1
Hamilton, J	1
Lendle, S	1
Fireman, BH	1
Liu, J	3
Wang, LN	3
Tokutome, M	1
Matoba, T	1
Nakano, Y	1
Okahara, A	1
Fujiwara, M	1
Koga, JI	1
Nakano, K	1
Tsutsui, H	2
Egashira, K	2
Hickson, RP	1
Cole, AL	1
Dusetzina, SB	1
Miao, S	1
Dong, X	1
Zhang, X	2
Jing, S	1
Xu, T	1
Wang, L	2
Du, X	1
Xu, H	1
Liu, Y	1
Dearborn-Tomazos, J	1
Ford, GA	3
Lovejoy, AM	4
Mori, D	1
Miyagawa, S	1
Matsuura, R	1
Sougawa, N	1
Fukushima, S	1
Ueno, T	1
Toda, K	1
Kuratani, T	1
Tomita, K	1
Maeda, N	1
Shimomura, I	1
Sawa, Y	1
Zhao, N	1
Yu, H	2
Sun, M	1
Zhang, Y	1
Xu, M	1
Gao, W	1
Vallarino, C	1
Perez, A	1
Fusco, G	1
Liang, H	1
Bron, M	1
Manne, S	1
Joseph, G	1
Yu, S	1
Green, JB	1
Bethel, MA	1
Paul, SK	1
Ring, A	1
Kaufman, KD	1
Shapiro, DR	1
Califf, RM	1
Holman, RR	1
Cao, W	1
Chen, J	1
Chen, Y	1
Chen, X	1
Liu, P	1
Lee, EJ	1
Marcy, TR	1
Brass, LM	2
Carolei, A	2
Parsons, MW	2
Peduzzi, PN	2
Ringleb, PA	1
Schwartz, GG	3
Tanne, D	2
Dangi-Garimella, S	1
Seong, JM	1
Choi, NK	1
Shin, JY	1
Chang, Y	1
Kim, YJ	1
Lee, J	1
Kim, JY	1
Park, BJ	1
Hou, J	2
Guo, T	1
Xing, Y	1
Zheng, S	1
Zhou, C	1
Huang, H	1
Long, H	1
Zhong, T	1
Wu, Q	1
Wang, J	1
Wang, T	1
Pladevall, M	2
Riera-Guardia, N	1
Margulis, AV	1
Varas-Lorenzo, C	1
Calingaert, B	1
Perez-Gutthann, S	1
Adams, HP	1
Berger, L	1
Clark, W	1
Coull, B	1
Kleindorfer, D	1
O'Leary, JR	1
Ringleb, P	1
Sen, S	1
Wang, D	1
Winder, TR	1
Mayor, S	1
Khodeer, DM	1
Zaitone, SA	1
Farag, NE	1
Moustafa, YM	1
Dagogo-Jack, S	1
Ismail-Beigi, F	1
Korytkowski, MT	1
Pratley, RE	1
Buse, JB	1
Kaul, S	1
Diamond, GA	1
Odom, J	1
Williamson, B	1
Carter, L	1
Ye, Y	6
Lin, Y	5
Perez-Polo, JR	6
Birnbaum, Y	6
Manickavasagam, S	1
Tieu, BC	1
Winkelmayer, WC	1
Setoguchi, S	1
Levin, R	1
Solomon, DH	1
Habib, ZA	1
Tzogias, L	1
Havstad, SL	1
Wells, K	1
Divine, G	1
Lanfear, DE	1
Tang, J	2
Krajenta, R	1
Williams, LK	1
Yasuda, S	1
Kobayashi, H	1
Iwasa, M	1
Kawamura, I	1
Sumi, S	1
Narentuoya, B	1
Yamaki, T	1
Ushikoshi, H	1
Nishigaki, K	1
Nagashima, K	1
Takemura, G	1
Fujiwara, T	1
Fujiwara, H	1
Minatoguchi, S	1
Kaneda, H	1
Shiono, T	1
Miyashita, Y	1
Takahashi, S	1
Taketani, Y	1
Domae, H	1
Matsumi, J	1
Mizuno, S	1
Minami, Y	1
Sugitatsu, K	1
Saito, S	1
Retnakaran, R	1
Zinman, B	1
Dore, DD	1
Trivedi, AN	1
Mor, V	1
Lapane, KL	1
Dormuth, CR	1
Maclure, M	1
Carney, G	1
Schneeweiss, S	1
Bassett, K	1
Wright, JM	1
Juurlink, DN	3
Gomes, T	2
Lipscombe, LL	2
Austin, PC	1
Hux, JE	2
Mamdani, MM	1
de Vries, CS	1
Russell-Jones, DL	1
Tzoulaki, I	1
Molokhia, M	1
Curcin, V	1
Little, MP	1
Millett, CJ	1
Ng, A	1
Hughes, RI	1
Khunti, K	1
Wilkins, MR	1
Majeed, A	1
Elliott, P	1
Ziyadeh, N	1
McAfee, AT	2
Koro, C	2
Landon, J	2
Arnold Chan, K	1
Keyes, KT	2
Zhang, C	1
Zhang, CF	1
Wadman, M	1
Ouellet-Hellstrom, R	1
MaCurdy, TE	1
Ali, F	1
Sholley, C	1
Worrall, C	1
Kelman, JA	1
Wertz, DA	1
Chang, CL	1
Sarawate, CA	1
Willey, VJ	1
Cziraky, MJ	1
Bohn, RL	1
Long, B	1
Qian, J	1
Loke, YK	1
Kwok, CS	1
Singh, S	1
Berthet, S	1
Olivier, P	1
Montastruc, JL	1
Lapeyre-Mestre, M	1
Kataoka, Y	1
Yagi, N	1
Kokubu, N	1
Kasahara, Y	1
Abe, M	1
Otsuka, Y	1
Shinmura, D	1
Togashi, I	1
Miyoshi, S	1
Nishiyama, N	1
Hida, N	1
Tsuji, H	1
Tsuruta, H	1
Segawa, K	1
Tsukada, Y	1
Ogawa, S	1
Umezawa, A	1
Doehner, W	1
Erdmann, E	7
Cairns, R	1
Clark, AL	1
Dormandy, JA	4
Ferrannini, E	1
Anker, SD	1
Wang, CC	1
Chen, WL	1
Kao, TW	1
Chang, YW	1
Loh, CH	1
Chou, CC	2
He, B	1
Ding, Y	1
Wang, H	1
Sun, Y	1
Shin, JH	1
Chen, B	1
Moorthy, G	1
Qiu, J	1
Desai, P	1
Wild, DJ	1
Yokoe, H	1
Yuasa, F	1
Yuyama, R	1
Murakawa, K	1
Miyasaka, Y	1
Yoshida, S	1
Tsujimoto, S	1
Sugiura, T	1
Iwasaka, T	1
Motola, D	1
Piccinni, C	1
Biagi, C	1
Raschi, E	1
Marra, A	1
Marchesini, G	1
Poluzzi, E	1
Nagashima, A	1
Watanabe, R	1
Ogawa, M	1
Suzuki, J	1
Masumura, M	1
Hishikari, K	1
Shimizu, T	1
Takayama, K	1
Hirata, Y	1
Nagai, R	1
Isobe, M	1
Tannen, R	1
Xie, D	1
Wang, X	1
Yu, M	1
Weiner, MG	1
Shiomi, T	1
Hayashidani, S	1
Suematsu, N	1
Ikeuchi, M	1
Wen, J	1
Ishibashi, M	1
Kubota, T	1
Takeshita, A	1
Thiemermann, C	3
Frantz, S	1
Hu, K	1
Widder, J	1
Bayer, B	1
Witzel, CC	1
Schmidt, I	1
Galuppo, P	1
Strotmann, J	1
Ertl, G	1
Bauersachs, J	1
Ito, H	1
Nakano, A	1
Kinoshita, M	1
Matsumori, A	1
Belcher, G	1
Lambert, C	1
Goh, KL	1
Edwards, G	1
Valbuena, M	1
Cho, L	1
Lewis, BE	1
Steen, LH	1
Leya, FS	1
Yki-Järvinen, H	1
Charbonnel, B	4
Eckland, DJ	1
Massi-Benedetti, M	4
Moules, IK	2
Skene, AM	3
Tan, MH	1
Lefèbvre, PJ	1
Murray, GD	1
Standl, E	2
Wilcox, RG	2
Wilhelmsen, L	1
Betteridge, J	1
Birkeland, K	1
Golay, A	1
Heine, RJ	1
Korányi, L	1
Laakso, M	1
Mokán, M	1
Norkus, A	1
Pirags, V	1
Podar, T	1
Scheen, A	1
Scherbaum, W	1
Schernthaner, G	1
Schmitz, O	1
Skrha, J	1
Smith, U	1
Taton, J	1
Fonseca, V	1
Jawa, A	1
Asnani, S	1
Wynne, AM	1
Mocanu, MM	1
Yellon, DM	1
Atar, S	1
Huang, MH	1
Uretsky, BF	1
Westerbacka, J	1
Yokoyama, J	1
Sutoh, N	1
Higuma, T	1
Horiuchi, D	1
Katoh, C	1
Yokota, T	1
Echizen, T	1
Sasaki, S	1
Hanada, H	1
Osanai, T	1
Okumura, K	1
Yates, J	1
Tan, M	1
Spanheimer, R	1
Strom, BL	1
Lewis, JD	1
Riche, DM	1
Dale, KM	1
Dormandy, J	1
Wilcox, R	2
Walker, AM	2
Lévesque, LE	1
Alter, DA	1
Scherbaum, WA	1
Kupfer, S	1
Koro, CE	1
Bourassa, MG	1
Berry, C	1
Li, J	1
Lang, MJ	1
Mao, XB	1
Tian, L	1
Feng, YB	1
Wayman, NS	1
Hattori, Y	1
McDonald, MC	1
Mota-Filipe, H	1
Cuzzocrea, S	1
Pisano, B	1
Chatterjee, PK	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Insulin Resistance Intervention After Stroke (IRIS) Trial[NCT00091949]	Phase 3	3,876 participants (Actual)	Interventional	2005-02-28	Completed
TECOS: A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Sitagliptin in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control[NCT00790205]	Phase 3	14,671 participants (Actual)	Interventional	2008-12-10	Completed
Preventive Effects of Ginseng Against Atherosclerosis and Subsequent Ischemic Stroke: A Randomized Controlled Trial[NCT02796664]		58 participants (Actual)	Interventional	2016-06-23	Completed
A Randomized,Placebo-controlled,Double-blind Trial of Phyllanthus Urinaria (Hepaguard®) in Adults With Nonalcoholic Steatohepatitis[NCT01210989]		60 participants (Actual)	Interventional	2010-05-31	Completed
Efficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes[NCT04943692]	Phase 3	500 participants (Anticipated)	Interventional	2021-08-31	Suspended (stopped due to Administrative decision of the investigation direction)
Safety and Efficacy of Metformin Glycinate vs Metformin Hydrochloride on Metabolic Control and Inflammatory Mediators in Type 2 Diabetes Patients[NCT01386671]	Phase 3	203 participants (Actual)	Interventional	2014-06-30	Completed
The Effect of Acupuncture on Insulin Sensitivity of Women With Polycystic Ovary Syndrome and Insulin Resistance: a Randomized Controlled Trial[NCT02491333]	Phase 3	342 participants (Actual)	Interventional	2015-08-31	Completed
PROspective PioglitAzone Clinical Trial In MacroVascular Events: A Macrovascular Outcome Study in Type 2 Diabetic Patients Comparing Pioglitazone With Placebo in Addition to Existing Therapy[NCT00174993]	Phase 3	4,373 participants (Actual)	Interventional	2001-05-31	Completed
A Prospective, Randomized, Parallel-group, Adaptive Design Phase IIb/III, Multicenter Study, to Assess the Efficacy of Polychemotherapy for Inducing Remission of Newly Diagnosed Type 2 Diabetes.[NCT04271189]	Phase 2/Phase 3	180 participants (Anticipated)	Interventional	2020-09-01	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Fatal or non-fatal acute myocardial infarction or unstable angina (NCT00091949)
Timeframe: 5 years

All Cause Mortality

Composite Outcome of Fatal or Non-fatal Stroke, Fatal or Non-fatal MI or Episode of Serious Congestive Heart Failure

Decline in Cognitive Status

Intervention	participants (Number)
Pioglitazone	206
Placebo	249

Intervention	participants (Number)
Pioglitazone	136
Placebo	146

Intervention	participants (Number)
Pioglitazone	206
Placebo	249

Change in modified mental status examination (3MS) score from baseline to exit. Theoretical range of 3MS scores is 0-100. Baseline scores ranged from 22-100. (NCT00091949)
Timeframe: Annual measures from baseline to exit (up to 5 years)

Development of Overt Diabetes

Fatal or Non-fatal Stroke Alone

Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction

Percent Incidence of All-cause Mortality (Intent to Treat Population)

Intervention	units on a scale (Mean)
Pioglitazone	0.27
Placebo	0.29

Intervention	participants (Number)
Pioglitazone	73
Placebo	149

Intervention	participants (Number)
Pioglitazone	127
Placebo	154

Intervention	participants (Number)
Pioglitazone	175
Placebo	228

Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause. (NCT00790205)
Timeframe: Up to 5 years

Percent Incidence of All-cause Mortality (Per Protocol Population)

Intervention	Percentage of participants (Number)
Sitagliptin	7.5
Placebo	7.3

Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause. (NCT00790205)
Timeframe: Up to 5 years

Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)

Intervention	Percentage of participants (Number)
Sitagliptin	4.7
Placebo	4.3

Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF. (NCT00790205)
Timeframe: Up to 5 years

Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)

Intervention	Percentage of participants (Number)
Sitagliptin	3.1
Placebo	3.1

Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)

Intervention	Percentage of participants (Number)
Sitagliptin	2.8
Placebo	2.8

Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)

Intervention	Percentage of participants (Number)
Sitagliptin	9.7
Placebo	13.2

Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)

Intervention	Percentage of participants (Number)
Sitagliptin	8.6
Placebo	11.9

Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)

Intervention	Percentage of participants (Number)
Sitagliptin	9.6
Placebo	9.6

CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)

Intervention	Percentage of participants (Number)
Sitagliptin	10.2
Placebo	10.2

CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)

Intervention	Percentage of participants (Number)
Sitagliptin	8.4
Placebo	8.3

Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)

Intervention	Percentage of participants (Number)
Sitagliptin	11.4
Placebo	11.6

In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.) (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)

Intervention	Percentage of participants (Number)
Sitagliptin	21.7
Placebo	27.9

In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent [AHA] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.) (NCT00790205)
Timeframe: Up to 5 years

Change From Baseline in HbA1c Over Time (Intent to Treat Population)

Intervention	Percentage of participants (Number)
Sitagliptin	18.9
Placebo	24.5

HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region. (NCT00790205)
Timeframe: Baseline and up to 4 years

Change From Baseline in HbA1c Over Time (Per Protocol Population)

Intervention	Percentage of HbA1c (Mean)
	Month 4: Sitagliptin, n= 6772; Placebo, n= 6738	Month 8: Sitagliptin, n= 6478; Placebo, n= 6414	Month 12: Sitagliptin, n= 6448; Placebo, n= 6384	Month 24: Sitagliptin, n= 6105; Placebo, n= 5975	Month 36: Sitagliptin, n= 3521; Placebo, n= 3439	Month 48: Sitagliptin, n= 1432; Placebo, n= 1383	Month 60: Sitagliptin, n= 123; Placebo, n= 128
Placebo	0.1	0.1	0.1	0.1	0.1	0.1	0.0
Sitagliptin	-0.3	-0.2	-0.2	-0.1	-0.1	0.0	0.0

Change From Baseline in Renal Function Over Time (Intent to Treat Population)

Intervention	Percentage of HbA1c (Mean)
	Month 4; Sitagliptin, n=6632, Placebo, n=6588	Month 8; Sitagliptin, n=6294, Placebo, n=6197	Month 12; Sitagliptin, n=6217, Placebo, n=6092	Month 24; Sitagliptin, n=5668, Placebo, n=5475	Month 36; Sitagliptin, n=3227, Placebo, n=3083	Month 48; Sitagliptin, n=1271, Placebo, n=1224	Month 60; Sitagliptin, n=106, Placebo, n=108
Placebo	0.1	0.1	0.1	0.2	0.1	0.1	0.0
Sitagliptin	-0.3	-0.3	-0.2	-0.1	-0.1	0.0	-0.1

Change in renal function based on eGFR using the MDRD method. (NCT00790205)
Timeframe: Baseline and up to 5 years

Change From Baseline in Renal Function Over Time (Per Protocol Population)

Intervention	mL/min/1.73 m^2 (Mean)
	Month 4; Sitagliptin, n=3949; Placebo, n=3977	Month 8; Sitagliptin, n=3687; Placebo, n=3648	Month 12; Sitagliptin, n=5082; Placebo, n=5015	Month 24; Sitagliptin, n=5157; Placebo, n=5071	Month 36; Sitagliptin, n=3037; Placebo, n=2942	Month 48; Sitagliptin, n=1237; Placebo, n=1210	Month 60; Sitagliptin, n=93; Placebo, n=106
Placebo	-0.8	-0.9	-0.5	-1.7	-1.6	-2.8	-5.7
Sitagliptin	-1.8	-2.4	-1.8	-3.2	-3.8	-4.0	-4.2

Change in renal function based on estimated glomerular filtration rate [eGFR] using the Modification of Diet in Renal Disease [MDRD] method. (NCT00790205)
Timeframe: Baseline and up to 5 years

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population)

Intervention	mL/min/1.73 m^2 (Mean)
	Month 4; Sitagliptin, n= 3859; Placebo, n= 3864	Month 8; Sitagliptin, n= 3562; Placebo, n= 3501	Month 12; Sitagliptin, n=4912, Placebo, n=4778	Month 24; Sitagliptin, n=4782, Placebo, n=4637	Month 36; Sitagliptin, n=2776, Placebo, n=2614	Month 48; Sitagliptin, n=1096, Placebo, n=1056	Month 60; Sitagliptin, n=79, Placebo, n=88
Placebo	-0.8	-0.9	-0.5	-1.7	-1.6	-2.8	-6.4
Sitagliptin	-1.9	-2.5	-1.8	-3.1	-3.7	-3.7	-3.5

Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value. (NCT00790205)
Timeframe: Baseline and up to 5 years

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population)

Intervention	g/mol Creatinine (Mean)
	Month 4; n=677, n=713	Month 8; n=658, n=624	Month 12; n=1167, n=1115	Month 24; n=1011, n=964	Month 36; n=537, n=553	Month 48; n=265, n=256	Month 60; n=14, n=18
Placebo	-1.4	0.5	1.2	3.1	3.9	1.6	6.4
Sitagliptin	-2.1	2.1	1.3	0.5	2.6	1.9	-2.5

Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value. (NCT00790205)
Timeframe: Baseline and up to 5 years

Drug Compliance

Intervention	g/mol Creatinine (Mean)
	Month 4; Sitagliptin, n=664; Placebo, n=688	Month 8; Sitagliptin, n=635; Placebo, n=597	Month 12; Sitagliptin, n=1126; Placebo, n=1059	Month 24; Sitagliptin, n=930; Placebo, n=892	Month 36; Sitagliptin, n=488; Placebo, n=513	Month 48; Sitagliptin, n=238; Placebo, n=233	Month 60; Sitagliptin, n=13; Placebo, n=17
Placebo	-1.4	0.2	1.2	3.2	4.0	1.5	4.8
Sitagliptin	-2.2	1.7	0.8	0.7	2.5	1.3	-2.7

We calculated average drug compliance based on the number of remained drugs at each follow-up. (NCT02796664)
Timeframe: At twelve months after randomization.

Modified Rankin Scale

Intervention	percentage of drug compliance (Mean)
Ginseng	97.4
Placebo	97.8

Presence of other cerebro-cardiovascular morbidity or mortality assessed by aggravation of patient status (modified Rankin Scale). The modified Rankin Scale is ranging from 0 to 5. The higher scale indicates the worse outcome. (NCT02796664)
Timeframe: Twelve months after randomization.

The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack

Intervention	Participants (Count of Participants)
	mRS 0	mRS 1	mRS 2	mRS 3	mRS 4	mRS 5
Ginseng	21	5	0	2	0	0
Placebo	22	1	0	1	0	0

The 1-year composite of cerebral ischemic stroke and transient ischemic attack downstream to an atherosclerotic lesion (NCT02796664)
Timeframe: Twelve months after randomization.

The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels.

Intervention	Participants (Count of Participants)
	Ischemic stroke	Transient ischemic attack
Ginseng	0	0
Placebo	0	1

The changes in volumetric blood flow (ml/sec) in intracranial vessels assessed by quantitative magnetic resonance angiography with noninvasive optimal vessel analysis. (NCT02796664)
Timeframe: At randomization and twelve months after randomization.

The Changes of White Matter Hyperintensities.

Intervention	Participants (Count of Participants)
	The flow change in steno-occlusive lesion72501839	The flow change in steno-occlusive lesion72501838	The flow change in collateral vessel72501838	The flow change in collateral vessel72501839
	Improved	No change	Aggravated
Ginseng	4
Placebo	5
Ginseng	17
Placebo	18
Placebo	1
Ginseng	7
Placebo	7
Placebo	9
Placebo	8

The changes of white matter hyperintensities, assessed by the Fazekas scale using brain magnetic resonance imaging. The Fazekas scale is a 4 point white matter disease severity scale with values ranging from 0 to 3. It quantifies the amount of white matter T2 hyperintense lesions each in periventricular white matter and deep white matter. Higher scales mean a worse white matter status. In the region of the periventricular white matter, 0 means absence of the lesion; 1, caps or pencil-thin lining lesion; 2, smooth halo lesion; 3, irregular high intense signal extending into the deep shite matter. In the region of the deep white matter, 0 means absence of the lesion; 1, punctate foci lesions; 2, beginning confluence; 3, large confluent hyperintense areas. (NCT02796664)
Timeframe: At randomization and twelve months after randomization.

Article	Year
Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. Diabetes, obesity & metabolism, 2022, Volume: 24, Issue:6 Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Insulin Re	2022
Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in people with stroke or transient ischaemic attack. The Cochrane database of systematic reviews, 2017, 12-02, Volume: 12 Topics: Cardiovascular Diseases; Carotid Artery Diseases; Humans; Hypoglycemic Agents; Insulin Resistance; I	2017
Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack. The Cochrane database of systematic reviews, 2014, Jan-08, Issue:1 Topics: Cardiovascular Diseases; Humans; Hypoglycemic Agents; Ischemic Attack, Transient; Myocardial Infarct	2014
Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack. The Cochrane database of systematic reviews, 2015, Oct-29, Issue:10 Topics: Cardiovascular Diseases; Humans; Hypoglycemic Agents; Ischemic Attack, Transient; Myocardial Infarct	2015
Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies. BMC cardiovascular disorders, 2016, Jan-15, Volume: 16 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Myocardi	2016
Rosiglitazone and cardiovascular risk. Current atherosclerosis reports, 2008, Volume: 10, Issue:5 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Meta-Analysis as To	2008
Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies. BMJ (Clinical research ed.), 2011, Mar-17, Volume: 342 Topics: Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Infarction; Piogli	2011
Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide. International journal of clinical practice, 2004, Volume: 58, Issue:9 Topics: Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Female; Glicl	2004
PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study. Vascular health and risk management, 2007, Volume: 3, Issue:4 Topics: Anticholesteremic Agents; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic An	2007

Article	Year
Adherence to study drug in a stroke prevention trial"?>. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2020, Volume: 29, Issue:10 Topics: Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Resi	2020
Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. JAMA neurology, 2017, 11-01, Volume: 74, Issue:11 Topics: Aged; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Resistanc	2017
Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial. JAMA neurology, 2019, 05-01, Volume: 76, Issue:5 Topics: Acute Coronary Syndrome; Aged; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hemo	2019
Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. American heart journal, 2013, Volume: 166, Issue:6 Topics: Aged; Aged, 80 and over; Angina, Unstable; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Doubl	2013
Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. American heart journal, 2014, Volume: 168, Issue:6 Topics: Adult; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; H	2014
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. The New England journal of medicine, 2016, Apr-07, Volume: 374, Issue:14 Topics: Aged; Brain Ischemia; Double-Blind Method; Female; Fractures, Bone; Humans; Hypoglycemic Agents; Ins	2016
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. The New England journal of medicine, 2016, Apr-07, Volume: 374, Issue:14 Topics: Aged; Brain Ischemia; Double-Blind Method; Female; Fractures, Bone; Humans; Hypoglycemic Agents; Ins	2016
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. The New England journal of medicine, 2016, Apr-07, Volume: 374, Issue:14 Topics: Aged; Brain Ischemia; Double-Blind Method; Female; Fractures, Bone; Humans; Hypoglycemic Agents; Ins	2016
Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. The New England journal of medicine, 2016, Apr-07, Volume: 374, Issue:14 Topics: Aged; Brain Ischemia; Double-Blind Method; Female; Fractures, Bone; Humans; Hypoglycemic Agents; Ins	2016
Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes care, 2016, Volume: 39, Issue:10 Topics: Aged; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agen	2016
Efficacy and safety of pioglitazone in patients with ST elevation myocardial infarction treated with primary stent implantation. Heart (British Cardiac Society), 2009, Volume: 95, Issue:13 Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis;	2009
Effect of pretreatment with pioglitazone on reperfusion injury in diabetic patients with acute myocardial infarction. Circulation journal : official journal of the Japanese Circulation Society, 2011, Volume: 75, Issue:8 Topics: Aged; Creatine Kinase; Diabetes Complications; Female; Follow-Up Studies; Humans; Hypoglycemic Agent	2011
Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study population. International journal of cardiology, 2012, Dec-15, Volume: 162, Issue:1 Topics: Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Hospitalization; Humans; Hypogl	2012
Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus. Journal of cardiovascular pharmacology, 2012, Volume: 59, Issue:6 Topics: Adiponectin; Aged; Baroreflex; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insul	2012
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet (London, England), 2005, Oct-08, Volume: 366, Issue:9493 Topics: Adult; Aged; Coronary Disease; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male;	2005
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet (London, England), 2005, Oct-08, Volume: 366, Issue:9493 Topics: Adult; Aged; Coronary Disease; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male;	2005
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet (London, England), 2005, Oct-08, Volume: 366, Issue:9493 Topics: Adult; Aged; Coronary Disease; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male;	2005
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet (London, England), 2005, Oct-08, Volume: 366, Issue:9493 Topics: Adult; Aged; Coronary Disease; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male;	2005
The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study. Journal of the American College of Cardiology, 2007, May-01, Volume: 49, Issue:17 Topics: Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypo	2007
Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). Diabetes care, 2007, Volume: 30, Issue:11 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Hear	2007
PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study. Vascular health and risk management, 2007, Volume: 3, Issue:4 Topics: Anticholesteremic Agents; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic An	2007
Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10). American heart journal, 2008, Volume: 155, Issue:4 Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents	2008

Article	Year
Pioglitazone-incorporated microspheres targeting macrophage polarization alleviates cardiac dysfunction after myocardial infarction. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2022, 10-04, Volume: 62, Issue:5 Topics: Animals; Delayed-Action Preparations; Macrophages; Microspheres; Myocardial Infarction; Myocardium;	2022
Which Patients With Ischemic Stroke and Insulin Resistance May Benefit From Pioglitazone Hydrochloride? JAMA neurology, 2017, 11-01, Volume: 74, Issue:11 Topics: Brain Ischemia; Humans; Insulin Resistance; Ischemic Attack, Transient; Myocardial Infarction; Piogl	2017
Prospective Postmarketing Surveillance of Acute Myocardial Infarction in New Users of Saxagliptin: A Population-Based Study. Diabetes care, 2018, Volume: 41, Issue:1 Topics: Acute Disease; Adamantane; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Female; Follow-Up Studies	2018
Peroxisome proliferator-activated receptor-gamma targeting nanomedicine promotes cardiac healing after acute myocardial infarction by skewing monocyte/macrophage polarization in preclinical animal models. Cardiovascular research, 2019, 02-01, Volume: 115, Issue:2 Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Drug Carriers; Injections, Intravenous; M	2019
Implications of Removing Rosiglitazone's Black Box Warning and Restricted Access Program on the Uptake of Thiazolidinediones and Dipeptidyl Peptidase-4 Inhibitors Among Patients with Type 2 Diabetes. Journal of managed care & specialty pharmacy, 2019, Volume: 25, Issue:1 Topics: Adult; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Labeling; Humans; Middle	2019
Detecting pioglitazone use and risk of cardiovascular events using electronic health record data in a large cohort of Chinese patients with type 2 diabetes. Journal of diabetes, 2019, Volume: 11, Issue:8 Topics: Case-Control Studies; China; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Follow-Up	2019
Pioglitazone strengthen therapeutic effect of adipose-derived regenerative cells against ischemic cardiomyopathy through enhanced expression of adiponectin and modulation of macrophage phenotype. Cardiovascular diabetology, 2019, 03-22, Volume: 18, Issue:1 Topics: Adiponectin; Adipose Tissue; Animals; Cadherins; Cardiomyopathies; Cell Transplantation; Cells, Cult	2019
MiRNA-711-SP1-collagen-I pathway is involved in the anti-fibrotic effect of pioglitazone in myocardial infarction. Science China. Life sciences, 2013, Volume: 56, Issue:5 Topics: Animals; Blotting, Western; Cells, Cultured; Collagen Type I; Fibrosis; Gene Expression; Gene Knockd	2013
Comparing pioglitazone to insulin with respect to cancer, cardiovascular and bone fracture endpoints, using propensity score weights. Clinical drug investigation, 2013, Volume: 33, Issue:9 Topics: Aged; Aged, 80 and over; Cohort Studies; Female; Fractures, Bone; Humans; Hypoglycemic Agents; Insul	2013
Advanced glycation end products promote heart failure through inducing the immune maturation of dendritic cells. Applied biochemistry and biotechnology, 2014, Volume: 172, Issue:8 Topics: Animals; Coculture Techniques; Dendritic Cells; Diabetes Complications; Dose-Response Relationship,	2014
The impact of pioglitazone on bladder cancer and cardiovascular events. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists, 2014, Volume: 29, Issue:8 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglitazone; Risk; U	2014
The Yin and the Yang of CV risks in patients with diabetes. The American journal of managed care, 2014, Volume: 20, Issue:8 Spec No. Topics: Adamantane; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptides	2014
Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study. PloS one, 2015, Volume: 10, Issue:5 Topics: Adult; Aged; Cardiovascular Diseases; Cardiovascular System; Cohort Studies; Diabetes Mellitus, Type	2015
Peroxisome Proliferator-Activated Receptor Gamma Promotes Mesenchymal Stem Cells to Express Connexin43 via the Inhibition of TGF-β1/Smads Signaling in a Rat Model of Myocardial Infarction. Stem cell reviews and reports, 2015, Volume: 11, Issue:6 Topics: Animals; Cell- and Tissue-Based Therapy; Connexin 43; Disease Models, Animal; Enzyme Activation; Mal	2015
Pioglitazone may reduce cardiovascular events in high risk patients with prediabetes. BMJ (Clinical research ed.), 2016, Feb-18, Volume: 352 Topics: Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglitazone; Prediabetic State; Stroke; Thiazol	2016
Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis. Canadian journal of physiology and pharmacology, 2016, Volume: 94, Issue:5 Topics: Adrenergic beta-Agonists; Animals; Apoptosis; Cardiotonic Agents; Diabetes Mellitus, Type 2; Diabeti	2016
The IRIS (Insulin Resistance Intervention after Stroke) trial: A new perspective on pioglitazone. Journal of diabetes, 2016, Volume: 8, Issue:5 Topics: Humans; Hypoglycemic Agents; Insulin Resistance; Ischemic Attack, Transient; Multicenter Studies as	2016
Are prescribing patterns of antidiabetic medications influenced by fears of litigation? Nature clinical practice. Endocrinology & metabolism, 2008, Volume: 4, Issue:8 Topics: Drug Prescriptions; Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglitazone; Rosiglitazone;	2008
Rosiglitazone and pioglitazone in the treatment of diabetes mellitus. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2008, Oct-01, Volume: 65, Issue:19 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglitazone; PPAR ga	2008
Oral glyburide, but not glimepiride, blocks the infarct-size limiting effects of pioglitazone. Cardiovascular drugs and therapy, 2008, Volume: 22, Issue:6 Topics: Administration, Oral; Animals; Body Weight; Coronary Vessels; Data Interpretation, Statistical; Deca	2008
Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice. American journal of physiology. Heart and circulatory physiology, 2008, Volume: 295, Issue:6 Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cardiovascular Agents; Cyclooxygenase 2; Cytochrome P-450 Enz	2008
Comparison of cardiovascular outcomes in elderly patients with diabetes who initiated rosiglitazone vs pioglitazone therapy. Archives of internal medicine, 2008, Nov-24, Volume: 168, Issue:21 Topics: Aged; Diabetes Complications; Diabetes Mellitus; Female; Heart Failure; Humans; Hypoglycemic Agents;	2008
Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis. Pharmacoepidemiology and drug safety, 2009, Volume: 18, Issue:6 Topics: Acute Disease; Cardiovascular Diseases; Cohort Studies; Data Interpretation, Statistical; Diabetes M	2009
Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction. American journal of physiology. Heart and circulatory physiology, 2009, Volume: 296, Issue:5 Topics: Androstadienes; Anilides; Animals; Blood Glucose; Blotting, Western; Decanoic Acids; Disease Models,	2009
Thiazolidinediones and clinical outcomes in type 2 diabetes. Lancet (London, England), 2009, Jun-20, Volume: 373, Issue:9681 Topics: Cholesterol, LDL; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Hospitalization; Humans; Hyd	2009
Association between extent of thiazolidinedione exposure and risk of acute myocardial infarction. Pharmacotherapy, 2009, Volume: 29, Issue:7 Topics: Aged; Aged, 80 and over; Case-Control Studies; Databases, Factual; Female; Humans; Hypoglycemic Agen	2009
Rosiglitazone and myocardial infarction in patients previously prescribed metformin. PloS one, 2009, Jun-27, Volume: 4, Issue:6 Topics: Aged; Case-Control Studies; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Femal	2009
Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ (Clinical research ed.), 2009, Aug-18, Volume: 339 Topics: Aged; Cohort Studies; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Hypoglycemic Agents;	2009
Rosiglitazone or pioglitazone in type 2 diabetes? BMJ (Clinical research ed.), 2009, Aug-18, Volume: 339 Topics: Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Infarction; Piogli	2009
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ (Clinical research ed.), 2009, Dec-03, Volume: 339 Topics: Administration, Oral; Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fractures, Bon	2009
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ (Clinical research ed.), 2009, Dec-03, Volume: 339 Topics: Administration, Oral; Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fractures, Bon	2009
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ (Clinical research ed.), 2009, Dec-03, Volume: 339 Topics: Administration, Oral; Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fractures, Bon	2009
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ (Clinical research ed.), 2009, Dec-03, Volume: 339 Topics: Administration, Oral; Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fractures, Bon	2009
The thiazolidinediones rosiglitazone and pioglitazone and the risk of coronary heart disease: a retrospective cohort study using a US health insurance database. Clinical therapeutics, 2009, Volume: 31, Issue:11 Topics: Adult; Aged; Cohort Studies; Coronary Disease; Death, Sudden; Female; Follow-Up Studies; Heart Rate;	2009
The myocardial infarct size-limiting effect of sitagliptin is PKA-dependent, whereas the protective effect of pioglitazone is partially dependent on PKA. American journal of physiology. Heart and circulatory physiology, 2010, Volume: 298, Issue:5 Topics: Animals; Blood Glucose; Blotting, Western; Body Weight; Culture Media; Cyclic AMP; Cyclic AMP-Depend	2010
Additive effect of TAK-491, a new angiotensin receptor blocker, and pioglitazone, in reducing myocardial infarct size. Cardiovascular drugs and therapy, 2010, Volume: 24, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Apoptosis; bcl-2-Associated X Protein; Blood Press	2010
Avandia outcome may signal change in epidemiologists' sway. Nature medicine, 2010, Volume: 16, Issue:6 Topics: Clinical Trials as Topic; Drug Approval; Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglit	2010
Rosiglitazone and the case for safety over certainty. JAMA, 2010, Jul-28, Volume: 304, Issue:4 Topics: Decision Making; Diabetes Mellitus, Type 2; Heart Failure; Hypoglycemic Agents; Meta-Analysis as Top	2010
Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA, 2010, Jul-28, Volume: 304, Issue:4 Topics: Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; H	2010
Risk of cardiovascular events and all-cause mortality in patients treated with thiazolidinediones in a managed-care population. Circulation. Cardiovascular quality and outcomes, 2010, Volume: 3, Issue:5 Topics: Female; Heart Failure; Humans; Male; Managed Care Programs; Middle Aged; Myocardial Infarction; Piog	2010
Pioglitazone limits myocardial infarct size, activates Akt, and upregulates cPLA2 and COX-2 in a PPAR-γ-independent manner. Basic research in cardiology, 2011, Volume: 106, Issue:3 Topics: Animals; Cyclooxygenase 2; Enzyme Activation; Gene Expression; Hypoglycemic Agents; Immunoblotting;	2011
Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database. BMC clinical pharmacology, 2011, May-24, Volume: 11 Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; Databases, Factual; Diabetes Mellitus, Type 2;	2011
Pretreatment of human mesenchymal stem cells with pioglitazone improved efficiency of cardiomyogenic transdifferentiation and cardiac function. Stem cells (Dayton, Ohio), 2011, Volume: 29, Issue:2 Topics: Adult; Animals; Bone Marrow Cells; Cell Differentiation; Cell Transdifferentiation; Cells, Cultured;	2011
Incidence of cardiovascular events in which 2 thiazolidinediones are used as add-on treatments for type 2 diabetes mellitus in a Taiwanese population. Clinical therapeutics, 2011, Volume: 33, Issue:12 Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Antihypertensive Agents; Cardiovascular Diseases; C	2011
Mining relational paths in integrated biomedical data. PloS one, 2011, Volume: 6, Issue:12 Topics: Algorithms; Computers; Data Collection; Data Mining; Databases, Factual; Humans; Hypoglycemic Agents	2011
Cardiovascular, ocular and bone adverse reactions associated with thiazolidinediones: a disproportionality analysis of the US FDA adverse event reporting system database. Drug safety, 2012, Apr-01, Volume: 35, Issue:4 Topics: Adverse Drug Reaction Reporting Systems; Bone and Bones; Cardiovascular System; Clinical Trials as T	2012
Different roles of PPAR-γ activity on physiological and pathological alteration after myocardial ischemia. Journal of cardiovascular pharmacology, 2012, Volume: 60, Issue:2 Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Anilides; Animals; Antihypertensive Agents; Ben	2012
A new "Comparative Effectiveness" assessment strategy using the THIN database: comparison of the cardiac complications of pioglitazone and rosiglitazone. Pharmacoepidemiology and drug safety, 2013, Volume: 22, Issue:1 Topics: Adult; Aged; Cohort Studies; Comparative Effectiveness Research; Databases, Factual; Diabetes Mellit	2013
Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation, 2002, Dec-10, Volume: 106, Issue:24 Topics: Administration, Oral; Animals; Aspartate Aminotransferases; Blood Glucose; Cytokines; Disease Models	2002
[Insulin sensitizer improves lipid profile. Infarct prevention for type 2 diabetic patients?]. MMW Fortschritte der Medizin, 2002, Dec-12, Volume: 144, Issue:50 Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agent	2002
Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure. British journal of pharmacology, 2004, Volume: 141, Issue:1 Topics: Animals; Disease Models, Animal; Heart Failure; Humans; Ligands; Mice; Myocardial Infarction; Piogli	2004
Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction. British journal of pharmacology, 2004, Volume: 141, Issue:1 Topics: Animals; Aorta; Blood Glucose; Body Weight; Chronic Disease; Collagen; Coronary Vessels; Cytokines;	2004
Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia/reperfusion injury in a rat model. Laboratory investigation; a journal of technical methods and pathology, 2003, Volume: 83, Issue:12 Topics: Animals; Chemokine CCL2; Disease Models, Animal; Hypoglycemic Agents; Intercellular Adhesion Molecul	2003
Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure. British journal of pharmacology, 2004, Volume: 142, Issue:6 Topics: Animals; Chemokine CCL2; Diabetes Mellitus, Type 2; Disease Models, Animal; Heart Diseases; Humans;	2004
Thiazolidinediones do not reduce target vessel revascularization in diabetic patients undergoing percutaneous coronary intervention. Cardiology, 2005, Volume: 104, Issue:2 Topics: Aged; Angioplasty, Balloon, Coronary; Cause of Death; Coronary Circulation; Coronary Stenosis; Diabe	2005
The PROactive study: some answers, many questions. Lancet (London, England), 2005, Oct-08, Volume: 366, Issue:9493 Topics: Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Myocardial Infarction; Pio	2005
Commentary: the PROactive study--the glass is half full. The Journal of clinical endocrinology and metabolism, 2006, Volume: 91, Issue:1 Topics: Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Disease Progression; Hum	2006
Pioglitazone mimics preconditioning in the isolated perfused rat heart: a role for the prosurvival kinases PI3K and P42/44MAPK. Journal of cardiovascular pharmacology, 2005, Volume: 46, Issue:6 Topics: Animals; Dose-Response Relationship, Drug; Hypoglycemic Agents; Ischemic Preconditioning, Myocardial	2005
PROactive study. Lancet (London, England), 2006, Mar-25, Volume: 367, Issue:9515 Topics: Clinical Trials as Topic; Endpoint Determination; Humans; Hypoglycemic Agents; Myocardial Infarction	2006
Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions. American journal of physiology. Heart and circulatory physiology, 2006, Volume: 291, Issue:3 Topics: Animals; Anticholesteremic Agents; Atorvastatin; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Drug S	2006
PROactive in patients with type 2 diabetes and previous myocardial infarction: swinging the sword of Damocles? Journal of the American College of Cardiology, 2007, May-01, Volume: 49, Issue:17 Topics: Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Infarction; Piogli	2007
Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty with the use of bare metal stent in patients with acute myocardial infarction and with type 2 diabetes mellitus or impaired glucose tolerance. Heart and vessels, 2007, Volume: 22, Issue:3 Topics: Angioplasty, Balloon, Coronary; Chi-Square Distribution; Coronary Angiography; Diabetes Mellitus, Ty	2007
Thiazolidinediones and cardiovascular disease. The Medical letter on drugs and therapeutics, 2007, Jul-16, Volume: 49, Issue:1265 Topics: Animals; Heart Failure; Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglitazone; Rosiglitaz	2007
In clarification. Pharmacoepidemiology and drug safety, 2007, Volume: 16, Issue:10 Topics: Humans; Hypoglycemic Agents; Myocardial Infarction; Pioglitazone; Rosiglitazone; Thiazolidinediones	2007
[Pioglitazone protects the type-2-diabetes patient from myocardial infarction and stroke]. MMW Fortschritte der Medizin, 2007, Aug-02, Volume: 149, Issue:31-32 Topics: Cholesterol, HDL; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Th	2007
A perspective on coronary revascularization in the PROactive 05 study. Journal of the American College of Cardiology, 2007, Oct-23, Volume: 50, Issue:17 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Myocardial Infarction; Myocardial Revascular	2007
Studies of diabetes, thiazolidinediones, and coronary heart disease. Pharmacoepidemiology and drug safety, 2007, Volume: 16, Issue:12 Topics: Coronary Disease; Diabetes Mellitus, Type 2; Hospitalization; Humans; Hypoglycemic Agents; Myocardia	2007
Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA, 2007, Dec-12, Volume: 298, Issue:22 Topics: Aged; Aged, 80 and over; Cause of Death; Diabetes Mellitus; Female; Heart Failure; Humans; Hypoglyce	2007
[Uncertainly after publications on glitazones. Elevated myocardial infarction risk is not a class effect]. MMW Fortschritte der Medizin, 2007, Dec-06, Volume: 149, Issue:49-50 Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Meta-Analysis as T	2007
Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000-2007. Pharmacoepidemiology and drug safety, 2008, Volume: 17, Issue:8 Topics: Cohort Studies; Coronary Disease; Databases, Factual; Diabetes Mellitus, Type 2; Humans; Hypoglycemi	2008
Prevention and noninvasive management of coronary atherosclerosis in patients with diabetes. Current atherosclerosis reports, 2008, Volume: 10, Issue:2 Topics: Antihypertensive Agents; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Melli	2008
Antiapoptosis and mitochondrial effect of pioglitazone preconditioning in the ischemic/reperfused heart of rat. Cardiovascular drugs and therapy, 2008, Volume: 22, Issue:4 Topics: Animals; Animals, Newborn; Apoptosis; bcl-2-Associated X Protein; Cardiovascular Agents; Caspase 3;	2008
[Type 2 diabetes. How can the infarction risk be reduced?]. MMW Fortschritte der Medizin, 2002, Feb-28, Volume: 144, Issue:9 Topics: Acarbose; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combinat	2002
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2002, Volume: 16, Issue:9 Topics: Adult; Animals; Cardiotonic Agents; Cell Adhesion Molecules; Cell Line; Cells, Cultured; Chemokine C	2002

Intervention	Participants (Count of Participants)
	Periventricular white matter72501836				Periventricular white matter72501837	Deep white matter72501837	Deep white matter72501836
	Fazekas scale 3	Fazekas scale 0	Fazekas scale 1	Fazekas scale 2
Placebo	11
Placebo	10
Ginseng	2
Ginseng	9
Placebo	6
Ginseng	15
Placebo	15
Ginseng	3
Placebo	2
Ginseng	1
Placebo	1

pioglitazone and Myocardial Infarction

Research Excerpts

Research

Studies (95)

Authors

Clinical Trials (9)

Trial Overview

Trial Outcomes

Acute Coronary Syndrome

All Cause Mortality

Composite Outcome of Fatal or Non-fatal Stroke, Fatal or Non-fatal MI or Episode of Serious Congestive Heart Failure

Decline in Cognitive Status

Development of Overt Diabetes

Fatal or Non-fatal Stroke Alone

Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction

Percent Incidence of All-cause Mortality (Intent to Treat Population)

Percent Incidence of All-cause Mortality (Per Protocol Population)

Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)

Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)

Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)

Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)

Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)

Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)

Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)

Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)

Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)

Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)

Change From Baseline in HbA1c Over Time (Intent to Treat Population)

Change From Baseline in HbA1c Over Time (Per Protocol Population)

Change From Baseline in Renal Function Over Time (Intent to Treat Population)

Change From Baseline in Renal Function Over Time (Per Protocol Population)

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population)

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population)

Drug Compliance

Modified Rankin Scale

The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack

The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels.

The Changes of White Matter Hyperintensities.

Reviews

Trials

Other Studies