SAN FRANCISCO — Chiglitazar, a novel PPARα/γ/δ pan-agonist, is a safe and effective treatment for patients with type 2 diabetes (T2D) and showed superior and sustainable glycemic control improvement and a well-tolerated safety profile, according to study results presented at the American Diabetes Association 79th Scientific Sessions, held June 7 to 11, 2019.
Previous phase 2 studies have reported the beneficial effects of chiglitazar on glycemic control and lipid profile, as well as a favorable safety profile. In this phase 3 study, the researchers assessed the efficacy and safety of chiglitazar compared with placebo in patients with T2D and insufficient glycemic control despite diet and exercise (ClinicalTrials.gov Identifier: NCT02121717).
The participants were randomly assigned to 1 of 3 groups: (1) chiglitazar 32 mg, once daily; (2) chiglitazar 48 mg, once daily; or (3) continuation of the planned treatment. The primary outcome measure was the change in glycated hemoglobin (HbA1c) from baseline after 24 weeks of treatment, with the superiority of each chiglitazar dose compared with placebo.
Of the 535 patients who received at least 1 dose of study medication, 167 patients were administered chiglitazar 32 mg, 166 patients received chiglitazar 48 mg, and 202 patients were given placebo.
At 24 weeks, both doses of chiglitazar were superior to placebo in HbA1c reduction. The mean change in HbA1c from baseline was -0.45% ± 1.22% with placebo, -1.30% ± 1.07% with chiglitazar 32 mg, and -1.52% ± 1.19% with chiglitazar 48 mg (chiglitazar 32 mg vs placebo: least squares [LS] mean difference, -0.87%; 95% CI, -1.10 to -0.65; chiglitazar 48 mg vs placebo: LS mean difference, -1.05; 95% CI, -1.29 to -0.81).
The effect was sustainable at 52 weeks with change in HbA1c from baseline to 52 weeks of -1.34% ± 1.162% with chiglitazar 32 mg and -1.57 ± 1.126% with chiglitazar 48 mg.
The percentage of patients achieving HbA1c <7%, a secondary study end point, was 18% in patients treated with placebo, 41% with chiglitazar 32 mg, and 53% with chiglitazar 48 mg.
Overall adverse events were comparable across study groups and reported in 71.9% of patients treated with chiglitazar 32 mg, 68.1% of patients treated with chiglitazar 48 mg, and 67.8% of patients administered placebo. Serious adverse events were documented in 2.4%, 4.8%, and 3.5% of patients, respectively. At 52 weeks, weight gain >5 kg and edema were relatively more common in patients treated with chiglitazar 48 mg (9.0% and 7.8%, respectively) compared with chiglitazar 32 mg (2.4% and 6.0%, respectively) or placebo (0% each).
Hypoglycemia was also relatively more common in the chiglitazar groups (at 24 weeks: 4.2% with chiglitazar 32 mg and 2.4% with chiglitazar 48 mg; at 52 weeks: 5.4% and 2.4%, respectively) compared with placebo.
Multiple authors disclosed associations with the pharmaceutical industry. Please see the original abstract for a full list of authors’ disclosures.
Ji L, Song W, Fang H, et al. Efficacy and safety of chiglitazar, a novel PPARα/γ/δ pan-agonist, in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 superiority trial (CMAP). Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. Oral Presentation 17-OR.