Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patien...Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
Metabolic cardiovascular diseases have become a global health concern,and some of their risk factors are linked to several metabolic disorders.They are the leading causes of death in developing countries.Adipose tissu...Metabolic cardiovascular diseases have become a global health concern,and some of their risk factors are linked to several metabolic disorders.They are the leading causes of death in developing countries.Adipose tissues secrete a variety of adipokines that participate in regulating metabolism and various pathophysiological processes.Adiponectin is the most abundant pleiotropic adipokine and can increase insulin sensitivity,improve atherosclerosis,have anti-inflammatory properties,and exert a cardioprotective effect.Low adiponectin con-centrations are correlated with myocardial infarction,coronary atherosclerotic heart disease,hypertrophy,hypertension,and other metabolic cardiovascular dysfunctions.However,the relationship between adiponectin and cardiovascular diseases is complex,and the specific mechanism of action is not fully understood.Our summary and analysis of these issues are ex-pected to contribute to future treatment options.展开更多
基金grants from Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002 and 2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金supported by grants from the National Natural Science Foundation of China(No.82000792)General Project of Chongqing Natural Science Foundation(China)(No.cstc2020jcyj-msxm0409)+2 种基金Chongqing Science and Technology Bureau and Health Commission of Chinese Medicine Technology Innovation and Application Development Project(China)(No.2020ZY013540)General Project of Graduate Education and Teaching Reform of Chongqing University,Chongqing,China(No.cquyjg20329)Science and Health Joint Project of Dazu District Science and Technology Bureau(China)(No.DZKJ,2022CCC1001).
文摘Metabolic cardiovascular diseases have become a global health concern,and some of their risk factors are linked to several metabolic disorders.They are the leading causes of death in developing countries.Adipose tissues secrete a variety of adipokines that participate in regulating metabolism and various pathophysiological processes.Adiponectin is the most abundant pleiotropic adipokine and can increase insulin sensitivity,improve atherosclerosis,have anti-inflammatory properties,and exert a cardioprotective effect.Low adiponectin con-centrations are correlated with myocardial infarction,coronary atherosclerotic heart disease,hypertrophy,hypertension,and other metabolic cardiovascular dysfunctions.However,the relationship between adiponectin and cardiovascular diseases is complex,and the specific mechanism of action is not fully understood.Our summary and analysis of these issues are ex-pected to contribute to future treatment options.
