pioglitazone and Weight Gain 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.

Research Excerpts

Excerpt	Relevance	Reference
"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)
" The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease."	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)
"The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone."	9.22	Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial. ( Bril, F; Cusi, K; Darland, C; Hardies, J; Hecht, J; Lomonaco, R; Musi, N; Orsak, B; Ortiz-Lopez, C; Portillo-Sanchez, P; Tio, F; Webb, A, 2016)
"This pilot study suggests limited efficacy for pioglitazone in the treatment of poorly controlled asthma in obesity, and also the potential for harm, given the weight gain in those assigned to active treatment, and the association between increased weight and worse outcomes in asthma."	9.20	A pilot randomized controlled trial of pioglitazone for the treatment of poorly controlled asthma in obesity. ( Black, K; DeSarno, M; Dixon, AE; Holguin, F; Lane, L; Subramanian, M, 2015)
"Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinically meaningful improvements in glycaemic control, without an additional risk of hypoglycaemia or weight gain (Clinical Trials Registry No: NCT 00996658)."	9.19	Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study. ( Bajaj, M; Gilman, R; Kempthorne-Rawson, J; Lewis-D'Agostino, D; Patel, S; Woerle, HJ, 2014)
"As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema."	9.15	Pioglitazone for diabetes prevention in impaired glucose tolerance. ( Banerji, M; Bray, GA; Buchanan, TA; Clement, SC; DeFronzo, RA; Henry, RR; Hodis, HN; Kitabchi, AE; Mack, WJ; Mudaliar, S; Musi, N; Ratner, RE; Reaven, PD; Schwenke, DC; Stentz, FB; Tripathy, D; Williams, K, 2011)
"To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM)."	9.14	Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome. ( Bray, GA; Greenway, FL; Gupta, AK; Smith, SR, 2009)
"Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes, is associated with weight gain."	9.14	Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone. ( Kushner, RF; Sujak, M, 2009)
"We investigated whether or not "low dose" metformin could prevent weight gain induced by pioglitazone."	9.13	Effects of pretreatment with low-dose metformin on metabolic parameters and weight gain by pioglitazone in Japanese patients with type 2 diabetes. ( Atsumi, Y; Funae, O; Hirata, T; Itoh, H; Kawai, T; Shimada, A; Tabata, M, 2008)
" Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH, but also leads to weight gain."	9.12	Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. ( Balas, B; Belfort, R; Cusi, K; Darland, C; Finch, J; Gastaldelli, A; Harrison, SA; Schenker, S, 2007)
"To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes."	8.95	Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis. ( Chen, TH; Lee, M; Liao, HW; Ovbiagele, B; Saver, JL; Wu, YL, 2017)
"Pioglitazone monotherapy and combinations were assessed in patients with type 2 diabetes and metabolic syndrome (Adult Treatment Panel III criteria) from four worldwide randomised, multicentre, double-blind studies."	8.82	Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria for metabolic syndrome. ( Fernandes, AW; Lester, JW, 2005)
"After 4-week pioglitazone treatment, the fasting blood glucose levels, glucose tolerance, and insulin sensitivity were significantly improved, but the body weight gain and fat mass were increased in DIO mice."	8.31	Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice. ( Cheng, L; Cheng, Y; Guo, W; Shen, Y; Wan, Z; Wang, W; Xu, F; Yu, P, 2023)
"The glycemic effect of pioglitazone is preserved even at lower doses, while the propensity to cause weight gain increases with dose."	7.81	Effect of Low (7.5 mg/day), Standard (15 mg/ day) and High (30 mg/day) Dose Pioglitazone Therapy on Glycemic Control and Weight Gain in Recently-Diagnosed Type 2 Diabetes Patients. ( Deogaonkar, N; Hoskote, SS; Joshi, SR; Kale, NJ; Panikar, V, 2015)
"Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10."	6.71	Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. ( Ezaki, O; Fujiwara, D; Ikeshima, E; Kanaya, T; Kondo, K; Odai, H; Oikawa, S; Shiraki, M; Tsuboyama-Kasaoka, N; Yajima, H, 2004)
"The combined treatment with INS 18 U/kg + PIO 5 mg/kg was more effective in preventing advanced cachexia in TB rats than each treatment alone, emerging as the best approach, considering the lower dosage and higher efficacy."	5.91	Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity. ( Bazotte, RB; Bertolini, GL; Biazi, GR; Cassolla, P; de Souza Galia, WB; de Souza, HM; Diaz, BF; Ferraz, LS; Frasson, IG; Kurauti, MA; Mareze-Costa, CE; Marmentini, C; Miksza, DR; Peres, SB, 2023)
"Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective."	5.36	Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice. ( Hirasawa, Y; Ito, M; Kyuki, K; Matsui, Y; Sugiura, T; Toyoshi, T, 2010)
"Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-gamma agonistic properties."	5.36	Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain. ( Aubert, G; Burnier, M; Dulloo, A; Mazzolai, L; Perregaux, C; Pralong, F; Zanchi, A, 2010)
"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)
" The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease."	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)
"The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone."	5.22	Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial. ( Bril, F; Cusi, K; Darland, C; Hardies, J; Hecht, J; Lomonaco, R; Musi, N; Orsak, B; Ortiz-Lopez, C; Portillo-Sanchez, P; Tio, F; Webb, A, 2016)
"This pilot study suggests limited efficacy for pioglitazone in the treatment of poorly controlled asthma in obesity, and also the potential for harm, given the weight gain in those assigned to active treatment, and the association between increased weight and worse outcomes in asthma."	5.20	A pilot randomized controlled trial of pioglitazone for the treatment of poorly controlled asthma in obesity. ( Black, K; DeSarno, M; Dixon, AE; Holguin, F; Lane, L; Subramanian, M, 2015)
"INT131 demonstrated dose-dependent reductions in HbA1c, equivalent to 45 mg pioglitazone, but with less fluid accumulation and weight gain, consistent with its SPPARM design."	5.19	Can a selective PPARγ modulator improve glycemic control in patients with type 2 diabetes with fewer side effects compared with pioglitazone? ( DePaoli, AM; Dunn, FL; Henry, RR; Higgins, LS; Mantzoros, C, 2014)
"Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinically meaningful improvements in glycaemic control, without an additional risk of hypoglycaemia or weight gain (Clinical Trials Registry No: NCT 00996658)."	5.19	Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study. ( Bajaj, M; Gilman, R; Kempthorne-Rawson, J; Lewis-D'Agostino, D; Patel, S; Woerle, HJ, 2014)
"As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema."	5.15	Pioglitazone for diabetes prevention in impaired glucose tolerance. ( Banerji, M; Bray, GA; Buchanan, TA; Clement, SC; DeFronzo, RA; Henry, RR; Hodis, HN; Kitabchi, AE; Mack, WJ; Mudaliar, S; Musi, N; Ratner, RE; Reaven, PD; Schwenke, DC; Stentz, FB; Tripathy, D; Williams, K, 2011)
" Vildagliptin provided additional HbA(1c) lowering to that achieved with metformin alone and comparable to that achieved with pioglitazone, with only pioglitazone causing weight gain."	5.14	Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. ( Bolli, G; Colin, L; Dotta, F; Goodman, M; Minic, B, 2009)
"To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM)."	5.14	Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome. ( Bray, GA; Greenway, FL; Gupta, AK; Smith, SR, 2009)
"Pioglitazone (PIO), a thiazolidinedione (TZD), is reported to be highly effective in the treatment of type 2 diabetes mellitus, but is associated with edema, heart failure, and weight gain."	5.14	Tolerability outcomes of a multicenter, observational, open-label, drug-surveillance study in patients with type 2 diabetes mellitus treated with pioglitazone for 2 years. ( Bailey, AL; Chan, JY; Grossman, LD; Parlan, G; Yee, G; Yu, M, 2009)
"Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes, is associated with weight gain."	5.14	Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone. ( Kushner, RF; Sujak, M, 2009)
"We investigated whether or not "low dose" metformin could prevent weight gain induced by pioglitazone."	5.13	Effects of pretreatment with low-dose metformin on metabolic parameters and weight gain by pioglitazone in Japanese patients with type 2 diabetes. ( Atsumi, Y; Funae, O; Hirata, T; Itoh, H; Kawai, T; Shimada, A; Tabata, M, 2008)
" Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH, but also leads to weight gain."	5.12	Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. ( Balas, B; Belfort, R; Cusi, K; Darland, C; Finch, J; Gastaldelli, A; Harrison, SA; Schenker, S, 2007)
"To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes."	4.95	Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis. ( Chen, TH; Lee, M; Liao, HW; Ovbiagele, B; Saver, JL; Wu, YL, 2017)
" The use of pioglitazone has been associated with an increased risk of bladder cancer, edema, heart failure, weight gain, and distal bone fractures in postmenopausal women."	4.89	[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus]. ( de Pablos-Velasco, PL; Valerón, PF, 2013)
"Pioglitazone monotherapy and combinations were assessed in patients with type 2 diabetes and metabolic syndrome (Adult Treatment Panel III criteria) from four worldwide randomised, multicentre, double-blind studies."	4.82	Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria for metabolic syndrome. ( Fernandes, AW; Lester, JW, 2005)
"After 4-week pioglitazone treatment, the fasting blood glucose levels, glucose tolerance, and insulin sensitivity were significantly improved, but the body weight gain and fat mass were increased in DIO mice."	4.31	Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice. ( Cheng, L; Cheng, Y; Guo, W; Shen, Y; Wan, Z; Wang, W; Xu, F; Yu, P, 2023)
"To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone."	3.81	The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes. ( Backus, C; Brosius, FC; Dauch, JR; Feldman, EL; Hayes, JM; Hinder, LM; Hur, J; Kretzler, M; Pennathur, S, 2015)
"The glycemic effect of pioglitazone is preserved even at lower doses, while the propensity to cause weight gain increases with dose."	3.81	Effect of Low (7.5 mg/day), Standard (15 mg/ day) and High (30 mg/day) Dose Pioglitazone Therapy on Glycemic Control and Weight Gain in Recently-Diagnosed Type 2 Diabetes Patients. ( Deogaonkar, N; Hoskote, SS; Joshi, SR; Kale, NJ; Panikar, V, 2015)
"To investigate the recovery of thiazolidinedione-induced body weight gain and haematopoietic changes after stopping pioglitazone treatment in patients with Type 2 diabetes."	3.80	Residual effect of reductions in red blood cell count and haematocrit and haemoglobin levels after 10-month withdrawal of pioglitazone in patients with Type 2 diabetes. ( Chen, BK; Feng, CC; Lee, MY; Lin, KD; Shin, SJ; Yu, ML, 2014)
"Pioglitazone was associated with a significant increase in body weight and edema."	3.75	Adverse effect of pioglitazone in military personnel and their families: a preliminary report. ( Benjasuratwong, Y; Patarakitvanit, S; Satyapan, N; Temboonkiat, S; Vudhironarit, T, 2009)
"The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes."	3.74	The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats. ( Ahn, CW; Cha, BS; Choi, SH; Kim, DJ; Kim, SK; Lee, HC; Lee, YJ; Lim, SK; Zhao, ZS, 2007)
"These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects."	3.74	The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. ( Borg, B; Ghany, M; Heller, T; Hoofnagle, JH; Kleiner, DE; Liang, TJ; Loomba, R; Lutchman, G; Modi, A; Premkumar, A; Promrat, K, 2007)
"The highest doses of rosiglitazone (10 mg/kg/day) or pioglitazone (30 mg/kg/day) were required to reduce fever peaks associated with acute or chronic inflammation, respectively, and to decrease arthritis severity."	3.74	Anti-inflammatory effect of antidiabetic thiazolidinediones prevents bone resorption rather than cartilage changes in experimental polyarthritis. ( Bianchi, A; Jouzeau, JY; Koufany, M; Moulin, D; Muresan, M; Netter, P; Sebillaud, S; Weryha, G, 2008)
" In a chronic-dosing study, equiefficacious antihyperglycemic doses of the PPAR gamma agonist pioglitazone and PPAR alpha/gamma dual activator ragaglitazar were administered to obesity-prone male rats."	3.72	Differential influences of peroxisome proliferator-activated receptors gamma and -alpha on food intake and energy homeostasis. ( Jensen, PB; Larsen, LK; Larsen, PJ; Sørensen, RV; Vrang, N; Wassermann, K; Wulff, EM, 2003)
"To determine the relationship between hypoglycemic activity and body weight gain induced by insulin sensitizers, we compared the effects of thiazolidinedione analogs (troglitazone and pioglitazone) and the oxadiazolidinedione analog (Z)-1,4-bis4[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phen oxy¿but-2-ene (YM440) in diabetic db/db mice."	3.70	The novel hypoglycemic agent YM440 normalizes hyperglycemia without changing body fat weight in diabetic db/db mice. ( Hirayama, R; Kurosaki, E; Nakano, R; Shibasaki, M; Shikama, H; Shimaya, A, 2000)
"Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis."	2.75	Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. ( Bass, NM; Brunt, EM; Chalasani, N; Clark, J; Diehl, AM; Hoofnagle, JH; Kleiner, DE; Kowdley, KV; Lavine, JE; McCullough, A; Neuschwander-Tetri, BA; Robuck, PR; Sanyal, AJ; Tonascia, J; Unalp, A; Van Natta, M, 2010)
"Muraglitazar is a dual (alpha/gamma) PPAR activator."	2.74	Efficacy and safety of muraglitazar: a double-blind, 24-week, dose-ranging study in patients with type 2 diabetes. ( Fiedorek, FT; Rubin, CJ; Viraswami-Appanna, K, 2009)
"Weight gain was probably not due to an increase in food intake, while REE per lean body mass decreased, suggesting a role for increased efficiency in fuel usage due to improved glycaemic control."	2.73	Weight gain in type 2 diabetes mellitus. ( Adams-Huet, B; Jacob, AN; Raskin, P; Salinas, K, 2007)
" Fasting and mean 7- and 8-point blood glucose profiles, blood lipid levels, plasminogen activator inhibitor levels, adverse events, and hypoglycemia frequency were also compared."	2.71	Efficacy and safety of biphasic insulin aspart 30 combined with pioglitazone in type 2 diabetes poorly controlled on glibenclamide (glyburide) monotherapy or combination therapy: an 18-week, randomized, open-label study. ( Chow, CC; Filipczak, R; Joshi, P; Lertoft, B; Rastam, J; Raz, I; Shaban, J; Stranks, S, 2005)
"Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10."	2.71	Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. ( Ezaki, O; Fujiwara, D; Ikeshima, E; Kanaya, T; Kondo, K; Odai, H; Oikawa, S; Shiraki, M; Tsuboyama-Kasaoka, N; Yajima, H, 2004)
" In these trials, adverse events were recorded, as were details of laboratory blood values, urine analysis, vital signs and electrocardiograms."	2.41	Safety profile of pioglitazone. ( Belcher, G; Hanefeld, M, 2001)
"The combined treatment with INS 18 U/kg + PIO 5 mg/kg was more effective in preventing advanced cachexia in TB rats than each treatment alone, emerging as the best approach, considering the lower dosage and higher efficacy."	1.91	Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity. ( Bazotte, RB; Bertolini, GL; Biazi, GR; Cassolla, P; de Souza Galia, WB; de Souza, HM; Diaz, BF; Ferraz, LS; Frasson, IG; Kurauti, MA; Mareze-Costa, CE; Marmentini, C; Miksza, DR; Peres, SB, 2023)
"Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective."	1.36	Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice. ( Hirasawa, Y; Ito, M; Kyuki, K; Matsui, Y; Sugiura, T; Toyoshi, T, 2010)
"Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-gamma agonistic properties."	1.36	Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain. ( Aubert, G; Burnier, M; Dulloo, A; Mazzolai, L; Perregaux, C; Pralong, F; Zanchi, A, 2010)

Research

Studies (59)

Authors

Clinical Trials (27)

Trial Overview

Trial Outcomes

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	32 (54.24)	29.6817
2010's	23 (38.98)	24.3611
2020's	4 (6.78)	2.80

Authors	Studies
Spence, JD	2
Viscoli, C	1
Kernan, WN	2
Young, LH	2
Furie, K	1
DeFronzo, R	1
Abdul-Ghani, M	1
Dandona, P	1
Inzucchi, SE	3
Yu, P	1
Wang, W	1
Guo, W	1
Cheng, L	1
Wan, Z	1
Cheng, Y	1
Shen, Y	1
Xu, F	1
Miksza, DR	1
Biazi, GR	1
Frasson, IG	1
de Souza Galia, WB	1
Ferraz, LS	1
Diaz, BF	1
Kurauti, MA	1
Marmentini, C	1
Mareze-Costa, CE	1
Peres, SB	1
Cassolla, P	1
Bertolini, GL	1
Bazotte, RB	1
de Souza, HM	1
Ito, Y	1
Yamamoto, M	1
Furukawa, S	1
Fukui, M	1
Morishita, K	1
Kitao, T	1
Shirahase, H	1
Mao, H	1
Lockyer, P	1
Li, L	1
Ballantyne, CM	1
Patterson, C	1
Xie, L	1
Pi, X	1
Panikar, V	1
Kale, NJ	1
Hoskote, SS	1
Deogaonkar, N	1
Joshi, SR	1
Valerón, PF	1
de Pablos-Velasco, PL	1
DePaoli, AM	1
Higgins, LS	1
Henry, RR	2
Mantzoros, C	1
Dunn, FL	1
Lin, KD	1
Lee, MY	1
Feng, CC	1
Chen, BK	1
Yu, ML	1
Shin, SJ	1
Bajaj, M	2
Gilman, R	1
Patel, S	1
Kempthorne-Rawson, J	1
Lewis-D'Agostino, D	1
Woerle, HJ	1
Abdul-Ghani, MA	1
Puckett, C	1
Triplitt, C	1
Maggs, D	1
Adams, J	1
Cersosimo, E	1
DeFronzo, RA	3
Liu, HJ	1
Zhang, CY	1
Song, F	1
Xiao, T	1
Meng, J	1
Zhang, Q	1
Liang, CL	1
Li, S	1
Wang, J	1
Zhang, B	1
Liu, YR	1
Sun, T	1
Zhou, HG	1
Hur, J	1
Dauch, JR	1
Hinder, LM	1
Hayes, JM	1
Backus, C	1
Pennathur, S	1
Kretzler, M	1
Brosius, FC	1
Feldman, EL	1
Boullu-Ciocca, S	1
Tassistro, V	1
Dutour, A	1
Grino, M	1
Dixon, AE	1
Subramanian, M	1
DeSarno, M	1
Black, K	1
Lane, L	1
Holguin, F	1
Viscoli, CM	1
Furie, KL	2
Gorman, M	1
Guarino, PD	1
Lovejoy, AM	1
Peduzzi, PN	1
Conwit, R	1
Brass, LM	1
Schwartz, GG	1
Adams, HP	1
Berger, L	1
Carolei, A	1
Clark, W	1
Coull, B	1
Ford, GA	1
Kleindorfer, D	1
O'Leary, JR	1
Parsons, MW	1
Ringleb, P	1
Sen, S	1
Tanne, D	1
Wang, D	1
Winder, TR	1
Cusi, K	2
Orsak, B	1
Bril, F	1
Lomonaco, R	1
Hecht, J	1
Ortiz-Lopez, C	1
Tio, F	1
Hardies, J	1
Darland, C	2
Musi, N	2
Webb, A	1
Portillo-Sanchez, P	1
Chen, YH	1
Tarng, DC	1
Chen, HS	1
Adachi, H	1
Katsuyama, H	1
Yanai, H	1
Liao, HW	1
Saver, JL	1
Wu, YL	1
Chen, TH	1
Lee, M	1
Ovbiagele, B	1
Negishi, M	1
Shimomura, K	1
Proks, P	1
Shimomura, Y	1
Mori, M	1
Kawai, T	1
Funae, O	1
Shimada, A	1
Tabata, M	1
Hirata, T	1
Atsumi, Y	1
Itoh, H	1
Vallon, V	1
Hummler, E	1
Rieg, T	1
Pochynyuk, O	1
Bugaj, V	1
Schroth, J	1
Dechenes, G	1
Rossier, B	1
Cunard, R	1
Stockand, J	1
Kushner, RF	1
Sujak, M	1
Grossman, LD	1
Parlan, G	1
Bailey, AL	1
Yee, G	1
Yu, M	1
Chan, JY	1
Gupta, AK	1
Smith, SR	2
Greenway, FL	1
Bray, GA	3
Kaku, K	1
Tanaka, S	1
Origasa, H	1
Kikuchi, M	1
Akanuma, Y	1
Bolli, G	1
Dotta, F	1
Colin, L	1
Minic, B	1
Goodman, M	1
Aubert, G	1
Burnier, M	1
Dulloo, A	1
Perregaux, C	1
Mazzolai, L	1
Pralong, F	1
Zanchi, A	1
Pasarica, M	1
Gowronska-Kozak, B	1
Burk, D	1
Remedios, I	1
Hymel, D	1
Gimble, J	1
Ravussin, E	1
Rubin, CJ	1
Viraswami-Appanna, K	1
Fiedorek, FT	1
Sanyal, AJ	1
Chalasani, N	1
Kowdley, KV	1
McCullough, A	1
Diehl, AM	1
Bass, NM	1
Neuschwander-Tetri, BA	1
Lavine, JE	1
Tonascia, J	1
Unalp, A	1
Van Natta, M	1
Clark, J	1
Brunt, EM	1
Kleiner, DE	2
Hoofnagle, JH	2
Robuck, PR	1
Matsui, Y	1
Hirasawa, Y	1
Sugiura, T	1
Toyoshi, T	1
Kyuki, K	1
Ito, M	1
Vudhironarit, T	1
Benjasuratwong, Y	1
Patarakitvanit, S	1
Temboonkiat, S	1
Satyapan, N	1
Henriksen, K	1
Byrjalsen, I	1
Qvist, P	1
Beck-Nielsen, H	1
Hansen, G	1
Riis, BJ	1
Perrild, H	1
Svendsen, OL	1
Gram, J	1
Karsdal, MA	1
Christiansen, C	1
Tripathy, D	1
Schwenke, DC	1
Banerji, M	1
Buchanan, TA	1
Clement, SC	1
Hodis, HN	1
Kitabchi, AE	1
Mack, WJ	1
Mudaliar, S	1
Ratner, RE	1
Williams, K	1
Stentz, FB	1
Reaven, PD	1
Derosa, G	1
Maffioli, P	1
Larsen, PJ	2
Jensen, PB	1
Sørensen, RV	1
Larsen, LK	1
Vrang, N	2
Wulff, EM	2
Wassermann, K	1
Papoushek, C	1
Suraamornkul, S	1
Hardies, LJ	1
Pratipanawatr, T	1
Yajima, H	1
Ikeshima, E	1
Shiraki, M	1
Kanaya, T	1
Fujiwara, D	1
Odai, H	1
Tsuboyama-Kasaoka, N	1
Ezaki, O	1
Oikawa, S	1
Kondo, K	1
Lester, JW	1
Fernandes, AW	1
Raz, I	1
Stranks, S	1
Filipczak, R	1
Joshi, P	1
Lertoft, B	1
Rastam, J	1
Chow, CC	1
Shaban, J	1
Majima, T	1
Komatsu, Y	1
Doi, K	1
Shigemoto, M	1
Takagi, C	1
Fukao, A	1
Corners, J	1
Nakao, K	1
Johansen, OE	1
Jørgensen, AP	1
Jacob, AN	1
Salinas, K	1
Adams-Huet, B	1
Raskin, P	1
Choi, SH	1
Zhao, ZS	1
Lee, YJ	1
Kim, SK	1
Kim, DJ	1
Ahn, CW	1
Lim, SK	1
Lee, HC	1
Cha, BS	1
Lutchman, G	1
Modi, A	1
Promrat, K	1
Heller, T	1
Ghany, M	1
Borg, B	1
Loomba, R	1
Liang, TJ	1
Premkumar, A	1
Balas, B	1
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Harrison, SA	1
Finch, J	1
Schenker, S	1
Gastaldelli, A	1
Sheffield, CA	1
Kane, MP	1
Busch, RS	1
Sleilati, GG	1
Leff, T	1
Bonnett, JW	1
Hegele, RA	1
Kanazawa, A	1
Kawamori, R	1
Koufany, M	1
Moulin, D	1
Bianchi, A	1
Muresan, M	1
Sebillaud, S	1
Netter, P	1
Weryha, G	1
Jouzeau, JY	1
Gotfredsen, CF	1
Brand, CL	1
Sturis, J	1
Knudsen, LB	1
Lykkegaard, K	1
Shimaya, A	1
Kurosaki, E	1
Nakano, R	1
Hirayama, R	1
Shibasaki, M	1
Shikama, H	1
Krische, D	1
de Souza, CJ	1
Eckhardt, M	1
Gagen, K	1
Dong, M	1
Chen, W	1
Laurent, D	1
Burkey, BF	1
Hanefeld, M	1
Belcher, G	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Randomized, Double-Blind, Placebo-Controlled, 24-Week Study to Evaluate the Efficacy and Safety of INT131 Besylate Compared to Pioglitazone in Subjects With Type 2 Diabetes[NCT00631007]	Phase 2	367 participants (Actual)	Interventional	2008-02-29	Completed
A Phase III, Randomised, Double Blind, Placebo Controlled Parallel Group Efficacy and Safety Study of Linagliptin 5 mg Administered Orally Once Daily Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metfor[NCT00996658]	Phase 3	278 participants (Actual)	Interventional	2009-10-31	Completed
Effectiveness and Tolerability of Novel, Initial Triple Combination Therapy With Xigduo (Dapagliflozin Plus Metformin) and Saxagliptin vs. Conventional Stepwise add-on Therapy in Drug-naïve Patients With Type 2 Diabetes[NCT02946632]	Phase 3	104 participants (Anticipated)	Interventional	2016-12-31	Not yet recruiting
A 16-wk, Uni-center, Randomized, Double-blind, Parallel, Phase 3b Trial to Evaluate Efficacy of Saxagliptin + Dapagliflozin vs.Dapagliflozin With Regard to EGP in T2DM With Insufficient Glycemic Control on Metformin+/-Sulfonylurea Therapy[NCT02613897]		56 participants (Actual)	Interventional	2016-01-31	Completed
Effect of Dapagliflozin on the Progression From Prediabetes to T2DM in Subjects With Myocardial Infarction[NCT03658031]	Phase 3	576 participants (Anticipated)	Interventional	2019-03-01	Not yet recruiting
A Randomized, Placebo-Controlled Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics[NCT00634036]	Phase 2	23 participants (Actual)	Interventional	2009-10-31	Completed
Preventive Effects of Ginseng Against Atherosclerosis and Subsequent Ischemic Stroke: A Randomized Controlled Trial[NCT02796664]		58 participants (Actual)	Interventional	2016-06-23	Completed
Insulin Resistance Intervention After Stroke (IRIS) Trial[NCT00091949]	Phase 3	3,876 participants (Actual)	Interventional	2005-02-28	Completed
Long-term Role of Pioglitazone in Non-Alcoholic Fatty Liver Disease (NAFLD) in Type 2 Diabetes Mellitus (T2DM).[NCT00994682]	Phase 4	176 participants (Actual)	Interventional	2008-12-31	Completed
Efficacy, Safety and Mechanism of Action of Lanifibranor (IVA337) in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease[NCT03459079]	Phase 2	54 participants (Anticipated)	Interventional	2018-08-14	Recruiting
Effect of Low-Dose Pioglitazone in Patients With Nonalcoholic Steatohepatitis (NASH)[NCT04501406]	Phase 2	166 participants (Anticipated)	Interventional	2020-12-15	Recruiting
The Effects of Thiazolidinedione on the Diabetic Retinopathy and Nephropathy[NCT01175486]	Phase 4	200 participants (Anticipated)	Interventional	2010-07-31	Recruiting
A Portion-controlled Diet Will Prevent Weight Gain in Diabetics Treated With ACTOS[NCT00219440]	Phase 4	60 participants (Anticipated)	Interventional	2003-02-28	Completed
A Randomized, Double-Blind, Dose Ranging, Dose Comparison-Controlled Trial to Determine the Safety and Efficacy of BMS-298585 in Subjects With Type 2 Diabetes[NCT00240383]	Phase 2/Phase 3	1,260 participants	Interventional	2002-05-31	Completed
A Randomised Controlled Trial of Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis[NCT01950884]	Phase 4	45 participants (Anticipated)	Interventional	2013-10-31	Enrolling by invitation
Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis: a Multicentre, Randomised, Placebo-controlled Trial[NCT03198572]	Phase 4	120 participants (Anticipated)	Interventional	2017-08-16	Recruiting
Efficacy of Nutritional Therapy With High Methionine Content in the Treatment of Non-alcoholic Fatty Liver: a Randomized Clinical Trial[NCT04450875]		121 participants (Actual)	Interventional	2015-03-24	Completed
Clinical Research Network in Nonalcoholic Steatohepatitis: Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)[NCT00063622]	Phase 3	247 participants (Actual)	Interventional	2005-01-31	Completed
A Single-arm, Open-label Clinical Study to Evaluate the Effect of SIM01 in Female Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)[NCT05885373]		40 participants (Anticipated)	Interventional	2023-03-01	Recruiting
An Randomized Open Label Trial on the Impact of 24 Weeks of Atorvastatin Therapy on Liver Fat Content and Abdominal Fat Content in Patients With Type 2 Diabetes Combined With High LDL-C and Non-alcoholic Fatty Liver Disease[NCT01720719]	Phase 4	120 participants (Anticipated)	Interventional	2013-05-31	Recruiting
A Randomized, Double-blind, Parallel-group, Placebo and Active Comparator (Pioglitazone)-Controlled Clinical Study to Determine the Efficacy and Safety of Balaglitazone in Patients With Type 2 Diabetes on Stable Insulin Therapy[NCT00515632]	Phase 3	409 participants (Actual)	Interventional	2007-07-31	Completed
Actos Now for Prevention of Diabetes (ACT NOW)[NCT00220961]	Phase 3	602 participants (Actual)	Interventional	2004-01-31	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
The Effect of Real Time Continuous Glucose Monitoring in Subjects With Pre-diabetes[NCT01741467]		110 participants (Actual)	Interventional	2012-05-31	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
[NCT00870012]		20 participants (Actual)	Interventional	2009-02-28	Completed
Role of Pioglitazone in the Treatment of Non-alcoholic Steatohepatitis (NASH)[NCT00227110]	Phase 4	55 participants (Actual)	Interventional	2002-10-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The change from baseline reflects the Week 24 FPG minus the Week 0 FPG with last observation carried forward. (NCT00631007)
Timeframe: Weeks 0-24

Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward

Intervention	mg/dL (Mean)
INT131 Besylate 0.5 mg	-0.3
INT131 Besylate 1 mg	-14.6
INT131 Besylate 2 mg	-28.9
INT131 Besylate 3 mg	-26.9
Pioglitazone HCl 45 mg	-33.2
Placebo	4.6

HbA1c is measured as percent. Thus this change from baseline reflects the week 24 HbA1c percent minus the Week 0 HbA1c percent (NCT00631007)
Timeframe: Weeks 0-24

Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks

Intervention	Percernt (Mean)
INT131 Besylate 0.5 mg	-0.3
INT131 Besylate 1 mg	-0.6
INT131 Besylate 2 mg	-0.9
INT131 Besylate 3 mg	-1.0
Pioglitazone HCl 45 mg	-0.9
Placebo	-0.1

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 12 (NCT00996658)
Timeframe: baseline, 12 weeks

Change From Baseline in Fasting Plasma Glucose (FPG) After 18 Weeks

Intervention	mg/dL (milligrams per deciliter) (Least Squares Mean)
Placebo Tablet	3.8
Linagliptin 5 mg Tablet	-7.1

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 18 (NCT00996658)
Timeframe: baseline, 18 weeks

Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks

Intervention	mg/dL (milligrams per deciliter) (Least Squares Mean)
Placebo Tablet	-2.4
Linagliptin 5 mg Tablet	-8.6

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 24 (NCT00996658)
Timeframe: baseline, 24 weeks

Change From Baseline in Fasting Plasma Glucose (FPG) After 6 Weeks

Intervention	mg/dL (milligrams per deciliter) (Least Squares Mean)
Placebo Tablet	0.1
Linagliptin 5 mg Tablet	-10.3

Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 6 (NCT00996658)
Timeframe: baseline, 6 weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks

Intervention	mg/dL (milligrams per deciliter) (Least Squares Mean)
Placebo Tablet	12.4
Linagliptin 5 mg Tablet	-3.3

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: baseline, 12 weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks

Intervention	Percentage (Least Squares Mean)
Placebo Tablet	-0.28
Linagliptin 5 mg Tablet	-0.82

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: baseline, 18 weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks

Intervention	Percentage (Least Squares Mean)
Placebo Tablet	-0.37
Linagliptin 5 mg Tablet	-0.91

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: baseline, 24 weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks

Intervention	Percentage (Least Squares Mean)
Placebo Tablet	-0.27
Linagliptin 5 mg Tablet	-0.84

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: baseline, 6 weeks

Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks

Intervention	Percentage (Least Squares Mean)
Placebo Tablet	-0.19
Linagliptin 5 mg Tablet	-0.60

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: 24 weeks

Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks

Intervention	Participants (Number)
	Responder (HbA1c < 6.5%)	Non-responder (HbA1c >= 6.5%)	Missing
Linagliptin 5 mg Tablet	34	143	1
Placebo Tablet	5	84	0

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: 24 weeks

Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks

Intervention	Participants (Number)
	Responder (HbA1c < 7.0%)	Non-responder (HbA1c >= 7.0%)	Missing
Linagliptin 5 mg Tablet	57	118	1
Placebo Tablet	12	75	0

Glycosylated hemoglobin is reported as a percentage of the total hemoglobin (NCT00996658)
Timeframe: 24 weeks

Change in BMI

Intervention	Participants (Number)
	Responder (reduction in HbA1c >= 0.5%)	Non-responder (reduction in HbA1c < 0.5%)	Missing
Linagliptin 5 mg Tablet	117	61	1
Placebo Tablet	44	45	0

Change in BMI (body mass index) from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Change in Body Weight

Intervention	Kg/m^2 (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-0.8
DAPA (Dapagliflozin Plus Placebo)	-0.66
PCB (Placebo Plus Placebo)	0.16

Change in body weight from baseline to 16 weeks (NCT02613897)
Timeframe: Baseline to 16 weeks

Change in Fasting Plasma Glucagon (FPG)

Intervention	Kg (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-2.28
DAPA (Dapagliflozin Plus Placebo)	-1.76
PCB (Placebo Plus Placebo)	0.26

A measure of the change in fasting plasma glucagon from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Change in Free Fatty Acids (FFA)

Intervention	mg/dl (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-28.52
DAPA (Dapagliflozin Plus Placebo)	26.89
PCB (Placebo Plus Placebo)	6.88

Measure of change in Free Fatty Acids from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Change in Glucose Oxidation

Intervention	mEq/L (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-0.06
DAPA (Dapagliflozin Plus Placebo)	-0.01
PCB (Placebo Plus Placebo)	0.00

Change in percentage of glucose oxidation from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Change in Lipid Oxidation

Intervention	percentage of oxidation (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-22.07
DAPA (Dapagliflozin Plus Placebo)	-46.54
PCB (Placebo Plus Placebo)	4.65

Change in lipid oxidation percentage from baseline to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

HBA1c

Intervention	percentage of oxidation (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-11.87
DAPA (Dapagliflozin Plus Placebo)	22.02
PCB (Placebo Plus Placebo)	-6.69

Change in blood glucose level measured over a 3 month period from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Mean Oral Glucose Tolerance Test (OGTT)

Intervention	percentage change in blood glucose level (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-1.67
DAPA (Dapagliflozin Plus Placebo)	-1.46
PCB (Placebo Plus Placebo)	0.44

Measure of change in OGTT from study start to 16 weeks (NCT02613897)
Timeframe: Change from baseline to 16 weeks

Change in Endogenous Glucose Production (EGP)

Intervention	mg/dl (Mean)
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	-49.62
DAPA (Dapagliflozin Plus Placebo)	-44.24
PCB (Placebo Plus Placebo)	20.26

All subjects received a Double-Tracer Oral Glucose Tolerance Test (OGTT) with 75g of glucose containing 14C-glucose together with intravenous primed-continuous infusion of 3(3H)-glucose for 240 minutes, at baseline (prior to) and after 16 weeks of therapy. Blood and urine samples were obtained during the OGTT to determine EGP. (NCT02613897)
Timeframe: Baseline and 16 weeks

Airway Reactivity

Intervention	mg/kg*min (Mean)
	Baseline Measurement	16 weeks
DAPA (Dapagliflozin Plus Placebo)	2.56	2.8
DAPA/SAXA (Dapagliflozin Plus Saxagliptin)	2.45	2.4
PCB (Placebo Plus Placebo)	1.95	2.15

Presence and degree of airway hyperresponsiveness assessed by methacholine challenge test. PC20= Methacholine dose at wich the FEV1 deops by > 20% from pre-methacholine baseline values. (NCT00634036)
Timeframe: 12 weeks

Exhaled Nitric Oxide Ppb

FEV1 % Predicted

Juniper Asthma Control Questionnaire

Intervention	mg/ml (Median)
Pioglitazone	5.08
Placebo	2.37

Intervention	ppb (Mean)
Pioglitazone	27.6
Placebo	30.8

Intervention	% predicted (Mean)
Pioglitazone	80.3
Placebo	85.2

The Juniper Asthma Control Questionnaire is a validated scale ranging from 0 to 6. Higher scores represent poorer asthma control. Values > 1.5 are compatible with poorly controlled asthma (NCT00634036)
Timeframe: 12 weeks

Drug Compliance

Intervention	Scores on a scale (Mean)
Pioglitazone	1.62
Placebo	1.82

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.

Acute Coronary Syndrome

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

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

Adipose Tissue Insulin Sensitivity

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

Suppression of free fatty acids by low dose insulin (i.e., percentage of reduction of plasma FFA with low dose insulin infusion compared to the baseline state). This was calculated as: 100*((plasma FFA without insulin - plasma FFA with insulin infusion)/plasma FFA without insulin). All measurements are obtained at the same time point during an euglycemic insulin clamp. (NCT00994682)
Timeframe: 18 months

Hepatic Insulin Sensitivity

Intervention	% of suppression of FFA (Mean)
Placebo	46.1
Pioglitazone	65.9

Suppression of endogenous glucose production (Supp EGP) by low dose insulin (i.e., percentage of reduction of EGP with low dose insulin infusion compared to the baseline state). This was calculated as: 100*((EGP without insulin - EGP with insulin infusion)/EGP without insulin). All measurements are obtained at the same time point during an euglycemic insulin clamp. (NCT00994682)
Timeframe: 18 months

Liver Fat by Magnetic Resonance and Spectroscopy (MRS).

Intervention	% of suppression of EGP (Mean)
Placebo	37.7
Pioglitazone	55.3

Liver fat content was calculated as the fat fraction: 100*(area under the curve [AUC] of fat peak / [AUC of fat peak + AUC of water peak]). (NCT00994682)
Timeframe: 18 months

Liver Histology (Using Kleiner et al Criteria, Hepatology 2005)

Intervention	percentage of fat in liver (Mean)
Placebo	11
Pioglitazone	7

"Number of patients with reduction of at least 2 points in the nonalcoholic fatty liver disease activity score (NAS) (with reduction in at least 2 different histological categories) without worsening of fibrosis. NAS is the sum of the separate scores for steatosis (0-3), hepatocellular ballooning (0-2) and lobular inflammation (0-3), and ranges from 0-8 .~The scoring system is based on the following grading:~Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis." (NCT00994682)
Timeframe: At 18 months

Number of Participants With Resolution of NASH

Intervention	Participants (Count of Participants)
Placebo	9
Pioglitazone	29

Resolution of NASH was defined as absence of NASH after 18 months of therapy in patients with definite NASH (presence of zone 3 accentuation of macrovesicular steatosis of any grade, hepatocellular ballooning of any degree, and lobular inflammatory infiltrates of any amount) at baseline. (NCT00994682)
Timeframe: Month 18

Osteoporotic Fractures

Intervention	Participants (Count of Participants)
Placebo	10
Pioglitazone	26

Number of patients with osteoporotic fractures (NCT00994682)
Timeframe: 18 and 36 months

Skeletal Muscle Insulin Sensitivity

Intervention	Participants (Count of Participants)
Pioglitazone	0
Placebo	0

Rate of glucose disappearance (Rd) during high-dose insulin infusion. The rate of plasma glucose disappearance was calculated using Steele's non-steady-state equation. (NCT00994682)
Timeframe: 18 months

Total Body Fat

Intervention	mg/kgLBM/min (Mean)
Placebo	5.4
Pioglitazone	9.6

Total body fat measured by dual-energy x-ray absorptiometry (DXA) (NCT00994682)
Timeframe: Months 18

Body Mass Index (BMI)

Bone Mineral Density

Intervention	Percentage of body weight that is fat (Mean)
Placebo	36
Pioglitazone	36

Bone mineral density measured at the levels of spine, femoral neck, hip, and wrist by DXA. (NCT00994682)
Timeframe: 18 and 36 months

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Homeostatic model assessment of insulin resistance (HOMA-IR) is a method for assessing insulin resistance (IR) from basal fasting plasma glucose (FPG) and fasting plasma insulin (FPI). It is calculated as (FPG x FPI)/405. (NCT00994682)
Timeframe: 18 and 36 months

Individual Histological Scores

"Number of patients with improvement of at least 1 grade in each of the histological parameters.~Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal, 1A = Mild, zone 3, perisinusoidal delicate fibrosis; 1B = Moderate, zone 3, perisinusoidal dense fibrosis; 1C = Portal/periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis" (NCT00994682)
Timeframe: Month 18

Liver Transaminases (AST and ALT).

Mean Individual Histological Scores

Mean change in individual scores compared to baseline. Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis (NCT00994682)
Timeframe: Baseline and Month 18

Mean Individual Histological Scores

Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis (NCT00994682)
Timeframe: Month 36

Plasma Biomarkers Relevant to Hepatic Inflammation, Apoptosis and Fibrosis (Adiponectin).

Plasma Biomarkers Relevant to Hepatic Inflammation, Apoptosis and Fibrosis (CK-18).

Prevention of the Onset of T2DM and/or Reversal From IFG/IGT to NGT in Non-diabetics.

Number of patients developing T2DM and number of patients regressing to NGT among patients with prediabetes (IFG/IGT). (NCT00994682)
Timeframe: 18 months

Number of Participants With Improvement in Fibrosis

Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. This secondary outcome measure is the number of participants that experienced a decrease in fibrosis score, which indicates improvement in fibrosis. (NCT00063622)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Hepatocellular Ballooning

Hepatocellular ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe hepatocellular ballooning. This secondary outcome measure is the number of participants that experienced a decrease in hepatocellular ballooning score, which indicates improvement in hepatocellular ballooning. (NCT00063622)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Lobular Inflammation

Lobular inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe lobular inflammation. This secondary outcome measure is the number of participants that experienced a decrease in lobular inflammation score, which indicates improvement in lobular inflammation. (NCT00063622)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Non-alcoholic Fatty Liver Disease (NAFLD) Activity Defined by Change in Standardized Scoring of Liver Biopsies at Baseline and After 96 Weeks of Treatment.

Total nonalcoholic fatty liver disease (NAFLD) activity was assessed on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (assessed on a scale of 0 to 3), lobular inflammation (assessed on a scale of 0 to 3), and hepatocellular ballooning (assessed on a scale of 0 to 2). The primary outcome was an improvement in histological findings from baseline to 96 weeks, which required an improvement by 1 or more points in the hepatocellular ballooning score; no increase in the fibrosis score; and either a decrease in the activity score for nonalcoholic fatty liver disease to a score of 3 or less or a decrease in the activity score of at least 2 points, with at least a 1-point decrease in either the lobular inflammation or steatosis score. (NCT00063622)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Steatosis

Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. This secondary outcome measure is the number of participants that experienced a decrease in steatosis score, which indicates improvement in steatosis. (NCT00063622)
Timeframe: baseline and 96 weeks

Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis

The criteria for nonalcoholic steatohepatitis was definite or possible steatohepatitis (assessed by a pathologist) with an activity score of 5 or more, or definite steatohepatitis (confirmed by two pathologists) with an activity score of 4. This secondary outcome measure is the number of participants who met this definition at baseline and did not meet this definition after 96 weeks of treatment and thus had a resolution of steatohepatitis. (NCT00063622)
Timeframe: baseline and 96 weeks

Change From Baseline in Fasting Plasma Glucose of 2.4 Years

Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)

Insulin sensitivity The Matsuda index was calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin), with higher numbers indicating better the insulin sensitivity. (NCT00220961)
Timeframe: Baseline versus 2.4 years

Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test

Change in Atherosclerosis

Prevention of Type 2 Diabetes

Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization (NCT00220961)
Timeframe: 2.4 years

Intervention	kg/m^2 (Mean)
	BMI Month 18	BMI Month 36
Pioglitazone	34.6	35.2
Placebo	34.6	36.7

Intervention	g/cm^2 (Mean)
	Spine BMD at month 18	Femoral Neck BMD at month 18	Hip BMD at month 18	Wrist BMD at month 18	Spine BMD at month 36	Femoral Neck BMD at month 36	Hip BMD at month 36	Wrist BMD at month 36
Pioglitazone	1.04	0.84	1.05	0.76	1.06	0.84	1.02	0.75
Placebo	1.10	0.86	1.05	0.78	1.10	0.84	1.06	0.77

Intervention	Arbitrary units (Mean)
	HOMA-IR month 18	HOMA-IR month 36
Pioglitazone	1.4	1.6
Placebo	4.3	2.3

Intervention	Participants (Count of Participants)
	Steatosis	Inflammation	Ballooning	Fibrosis
Pioglitazone	35	25	25	20
Placebo	13	11	12	13

Intervention	U/L (Mean)
	ALT at month 18	AST at month 18	ALT at month 36	AST at month 36
Pioglitazone	27	29	27	27
Placebo	44	38	32	30

Intervention	μg/ml (Mean)
	Adiponectin month 18	Adiponectin month 36
Pioglitazone	22.8	24.2
Placebo	9.1	24.0

Intervention	Participants (Count of Participants)
	Patients developing T2DM	Patients regressing to NGT
Pioglitazone	1	10
Placebo	2	1

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
[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus]. Medicina clinica, 2013, Volume: 141 Suppl 2 Topics: Contraindications; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Comb	2013
Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis. BMJ open, 2017, 01-05, Volume: 7, Issue:1 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Edema; Fractures, Bone; Humans; Hypoglycemic Age	2017
Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists on glycemic control, lipid profile and cardiovascular risk. Current molecular pharmacology, 2012, Volume: 5, Issue:2 Topics: Atherosclerosis; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Ins	2012
The "glitazones": rosiglitazone and pioglitazone. Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2003, Volume: 25, Issue:10 Topics: Contraindications; Diabetes Mellitus, Type 2; Drug Interactions; Female; Heart Failure; Humans; Hypo	2003
Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria for metabolic syndrome. International journal of clinical practice, 2005, Volume: 59, Issue:2 Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combinatio	2005
[Adverse effects of insulin sensitisers and biguanides]. Nihon rinsho. Japanese journal of clinical medicine, 2007, Oct-28, Volume: 65 Suppl 8 Topics: Acidosis, Lactic; Animals; Biguanides; Capillary Permeability; Chemical and Drug Induced Liver Injur	2007
The glitazones: proceed with caution. The Western journal of medicine, 2000, Volume: 173, Issue:1 Topics: Chromans; Diabetes Mellitus, Type 2; Drug Evaluation; Humans; Hypoglycemic Agents; Liver; Pioglitazo	2000
Safety profile of pioglitazone. International journal of clinical practice. Supplement, 2001, Issue:121 Topics: Cardiovascular System; Edema; Humans; Hypoglycemic Agents; Pioglitazone; Randomized Controlled Trial	2001

Article	Year
Pioglitazone-Enhanced Brown Fat Whitening Contributes to Weight Gain in Diet-Induced Obese Mice. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2023, Volume: 131, Issue:11 Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Diabetes Mellitus, Type 2; Diet, High-Fat; Gl	2023
Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity. Pharmacological reports : PR, 2023, Volume: 75, Issue:6 Topics: Animals; Cachexia; Hypoglycemic Agents; Insulin; Insulin Resistance; Neoplasms; Pioglitazone; Rats;	2023
Effects of KY-903, a Novel Tetrazole-Based Peroxisome Proliferator-Activated Receptor γ Modulator, in Male Diabetic Mice and Female Ovariectomized Rats. Biological & pharmaceutical bulletin, 2021, Volume: 44, Issue:5 Topics: 3T3-L1 Cells; Adipogenesis; Adiponectin; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diet, Hi	2021
Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ. Nature communications, 2017, 04-10, Volume: 8 Topics: Adipokines; Animals; CD36 Antigens; Cholesterol; Diet, High-Fat; Endocytosis; Endothelial Cells; Gen	2017
Effect of Low (7.5 mg/day), Standard (15 mg/ day) and High (30 mg/day) Dose Pioglitazone Therapy on Glycemic Control and Weight Gain in Recently-Diagnosed Type 2 Diabetes Patients. The Journal of the Association of Physicians of India, 2015, Volume: 63, Issue:11 Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; F	2015
Residual effect of reductions in red blood cell count and haematocrit and haemoglobin levels after 10-month withdrawal of pioglitazone in patients with Type 2 diabetes. Diabetic medicine : a journal of the British Diabetic Association, 2014, Volume: 31, Issue:11 Topics: Aged; Anemia; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Drug Monitoring; Erythrocy	2014
A Novel Partial Agonist of Peroxisome Proliferator-Activated Receptor γ with Excellent Effect on Insulin Resistance and Type 2 Diabetes. The Journal of pharmacology and experimental therapeutics, 2015, Volume: 353, Issue:3 Topics: 3-Mercaptopropionic Acid; Animals; Blood Glucose; Cell Line; Cell Survival; Diabetes Mellitus, Exper	2015
The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes. Diabetes, 2015, Volume: 64, Issue:9 Topics: Animals; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Models, Animal; Hypo	2015
Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations. Endocrine, 2015, Volume: 50, Issue:3 Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adiponectin; Adipose Tissue; Animals; Drug Evaluation,	2015
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
The low dose (7.5mg/day) pioglitazone is beneficial to the improvement in metabolic parameters without weight gain and an increase of risk for heart failure. International journal of cardiology, 2017, Jan-15, Volume: 227 Topics: Aged; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Middle Ag	2017
Thiazolidinedione-induced fluid retention is independent of collecting duct alphaENaC activity. Journal of the American Society of Nephrology : JASN, 2009, Volume: 20, Issue:4 Topics: Animals; Epithelial Sodium Channels; Kidney Medulla; Kidney Tubules, Collecting; Mice; Patch-Clamp T	2009
Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain. Metabolism: clinical and experimental, 2010, Volume: 59, Issue:1 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Anorexia; Benzimidazoles; Benzoates; Blood Glucose	2010
Adipose tissue collagen VI in obesity. The Journal of clinical endocrinology and metabolism, 2009, Volume: 94, Issue:12 Topics: Adipocytes; Adipose Tissue; Adolescent; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocyt	2009
Metformin reduces body weight gain and improves glucose intolerance in high-fat diet-fed C57BL/6J mice. Biological & pharmaceutical bulletin, 2010, Volume: 33, Issue:6 Topics: Animals; Blood Glucose; Body Weight; Dietary Fats; Energy Intake; Glucagon-Like Peptide 1; Glucose I	2010
Adverse effect of pioglitazone in military personnel and their families: a preliminary report. Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2009, Volume: 92 Suppl 1 Topics: Adult; Aged; Diabetes Mellitus, Type 2; Edema; Family; Female; Humans; Hypoglycemic Agents; Incidenc	2009
Differential influences of peroxisome proliferator-activated receptors gamma and -alpha on food intake and energy homeostasis. Diabetes, 2003, Volume: 52, Issue:9 Topics: Adipose Tissue; Animals; Biomarkers; Blood Glucose; Eating; Energy Metabolism; Fenofibrate; Gene Exp	2003
Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 2004, Volume: 28, Issue:6 Topics: Blood Glucose; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose; Hormones, Ect	2004
[Glitazone treatment of type 2 diabetes mellitus]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2006, Aug-10, Volume: 126, Issue:15 Topics: Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged	2006
The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats. Diabetes/metabolism research and reviews, 2007, Volume: 23, Issue:5 Topics: Animals; Diabetes Mellitus, Type 2; Disease Models, Animal; Hypoglycemic Agents; Metformin; Pioglita	2007
The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.), 2007, Volume: 46, Issue:2 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Female; Humans; Insulin Resis	2007
The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.), 2007, Volume: 46, Issue:2 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Female; Humans; Insulin Resis	2007
The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.), 2007, Volume: 46, Issue:2 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Female; Humans; Insulin Resis	2007
The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.), 2007, Volume: 46, Issue:2 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Female; Humans; Insulin Resis	2007
Off-label use of exenatide for the management of insulin-resistant type 1 diabetes mellitus in an obese patient with human immunodeficiency virus infection. Pharmacotherapy, 2007, Volume: 27, Issue:10 Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exenatide; HIV Infections; Humans; Hypo	2007
Efficacy and safety of pioglitazone in treatment of a patient with an atypical partial lipodystrophy syndrome. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2007, Volume: 13, Issue:6 Topics: Adult; Clofibric Acid; Female; Humans; Hypoglycemic Agents; Insulin; Lipodystrophy, Familial Partial	2007
Anti-inflammatory effect of antidiabetic thiazolidinediones prevents bone resorption rather than cartilage changes in experimental polyarthritis. Arthritis research & therapy, 2008, Volume: 10, Issue:1 Topics: Adiponectin; Adipose Tissue; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Biomarkers;	2008
Combination of the insulin sensitizer, pioglitazone, and the long-acting GLP-1 human analog, liraglutide, exerts potent synergistic glucose-lowering efficacy in severely diabetic ZDF rats. Diabetes, obesity & metabolism, 2008, Volume: 10, Issue:4 Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combina	2008
The novel hypoglycemic agent YM440 normalizes hyperglycemia without changing body fat weight in diabetic db/db mice. Metabolism: clinical and experimental, 2000, Volume: 49, Issue:3 Topics: 3T3 Cells; Adipose Tissue; Animals; Blood Glucose; Cell Differentiation; Chromans; Diabetes Mellitus	2000
Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. Diabetes, 2001, Volume: 50, Issue:8 Topics: Adipocytes; Adipose Tissue; Analysis of Variance; Animals; Blood Glucose; Cell Division; Cell Size;	2001

pioglitazone and Weight Gain

Research Excerpts

Research

Studies (59)

Authors

Clinical Trials (27)

Trial Overview

Trial Outcomes

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward.

Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward

Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks

Change From Baseline in Fasting Plasma Glucose (FPG) After 18 Weeks

Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks

Change From Baseline in Fasting Plasma Glucose (FPG) After 6 Weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks

Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks

Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks

Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks

Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks

Change in BMI

Change in Body Weight

Change in Fasting Plasma Glucagon (FPG)

Change in Free Fatty Acids (FFA)

Change in Glucose Oxidation

Change in Lipid Oxidation

HBA1c

Mean Oral Glucose Tolerance Test (OGTT)

Change in Endogenous Glucose Production (EGP)

Airway Reactivity

Exhaled Nitric Oxide Ppb

FEV1 % Predicted

Juniper Asthma Control Questionnaire

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.

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

Adipose Tissue Insulin Sensitivity

Hepatic Insulin Sensitivity

Liver Fat by Magnetic Resonance and Spectroscopy (MRS).

Liver Histology (Using Kleiner et al Criteria, Hepatology 2005)

Number of Participants With Resolution of NASH

Osteoporotic Fractures

Skeletal Muscle Insulin Sensitivity

Total Body Fat

Body Mass Index (BMI)

Bone Mineral Density

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Individual Histological Scores

Liver Transaminases (AST and ALT).

Mean Individual Histological Scores

Mean Individual Histological Scores

Plasma Biomarkers Relevant to Hepatic Inflammation, Apoptosis and Fibrosis (Adiponectin).

Plasma Biomarkers Relevant to Hepatic Inflammation, Apoptosis and Fibrosis (CK-18).

Prevention of the Onset of T2DM and/or Reversal From IFG/IGT to NGT in Non-diabetics.

Number of Participants With Improvement in Fibrosis

Number of Participants With Improvement in Hepatocellular Ballooning

Number of Participants With Improvement in Lobular Inflammation

Number of Participants With Improvement in Non-alcoholic Fatty Liver Disease (NAFLD) Activity Defined by Change in Standardized Scoring of Liver Biopsies at Baseline and After 96 Weeks of Treatment.

Number of Participants With Improvement in Steatosis

Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis

Change From Baseline in Fasting Plasma Glucose of 2.4 Years

Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)

Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test

Change in Atherosclerosis

Prevention of Type 2 Diabetes

Reviews

Trials

Other Studies