Impact of chiglitazar on glycemic control in type 2 diabetic patients with metabolic syndrome and insulin resistance: A pooled data analysis from two phase III trials.

BACKGROUND: To evaluate the glycemic control effects of vhiglitazar (carfloglitazar), a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes mellitus (T2DM) with metabolic syndrome (MetS) or insulin resistance (IR) using pooled data analysis of two phase III clinical trials. METHODS: Data were collected from two randomized phase III clinical trials in China, comparing chiglitazar to placebo or sitagliptin in T2DM patients. The MetS was defined by the Adult Treatment Panel III MetS criteria, and IR was defined by homeostatic model assessment for insulin resistance (HOMA-IR) ≥4.31 (male) or 4.51 (female). The main end point of this analysis was glycemic control in the different arms within each subgroup. RESULTS: In the MetS subgroup, changes in glycated hemoglobin (HbA1c) from baseline at week 24 in the chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg arms were -1.44%, -1.68%, and -1.37%, respectively; p < .05 was obtained when chiglitazar 48 mg was compared with sitagliptin. In the IR subgroup, the changes in HbA1c were -1.58%, -1.56%, and -1.26% in chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg arms, respectively; p < .05 was obtained when chiglitazar 32 mg was compared with sitaligptin. The two doses of chiglitazar demonstrated a greater reduction in fasting plasma glucose and 2 h postprandial plasma glucose than sitagliptin in the pooled population and in the MetS and IR subgroups. CONCLUSIONS: Chiglitazar shows promising efficacy for glycemic control in patients with T2DM associated with MetS or IR. Further prospective trials are required to validate these findings.

Efficacy and safety of chiglitazar, a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial (CMAP).

Chiglitazar (Carfloglitazar) is a novel non-thiazolidinedione (TZD) structured peroxisome proliferator-activated 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 A1c (HbA1c) 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 HbA1c, 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.