SAN FRANCISCO — Chiglitazar, a novel PPARα/γ/δ pan-agonist, was found to have a noninferior effect to sitagliptin on glycemic control with a tolerable safety profile, according to study results presented at the American Diabetes Association 79th Scientific Sessions, held June 7 to 11, 2019 in San Francisco, California.
Previous phase 2 studies have reported the safety and efficacy of chiglitazar with improvement in glycemic control and lipid profile in type 2 diabetes (T2D). The goal of the study was to assess the efficacy and safety of chiglitazar compared with sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with T2D and insufficient glycemic control with diet and exercise.
The participants were randomly assigned to 1 of 3 groups: (1) chiglitazar 32 mg once daily, (2) chiglitazar 48 mg once daily, or (3) sitagliptin 100 mg once daily. Treatment was given for 24 weeks and the primary outcome measure was the change in hemoglobin A1c (HbA1c) from baseline to after 24 weeks of treatment to assess noninferiority of each chiglitazar dose compared with sitagliptin.
Of 739 patients administered ≥1 dose of study medication, 245 patients received chiglitazar 32 mg, 246 patients received chiglitazar 48 mg, and 248 patients received sitagliptin 100 mg.
At 24 weeks, chiglitazar at both doses had a similar effect on HbA1c reduction compared with sitagliptin. The mean change in HbA1c from baseline was −1.39%±1.12% with sitagliptin, −1.38%±1.16% with chiglitazar 32 mg, and −1.47%±1.21% with chiglitazar 48 mg (chiglitazar 32 mg vs sitagliptin: least squares (LS) mean difference, −0.04%; 95% CI, −0.22% to 0.15%; chiglitazar 48 mg vs sitagliptin: LS mean difference, −0.08%; 95% CI, −0.27% to 0.10%).
Percentage of patients achieving HbA1c <7% — one of the secondary end points of the study — was 45% in patients treated with sitagliptin, 49% with chiglitazar 32 mg, and 52% with chiglitazar 48 mg.
Overall adverse events were comparable across study groups and reported in 66.9% of patients receiving chiglitazar 32 mg, 63.4% of patients receiving chiglitazar 48 mg, and 65.3% of patients receiving sitagliptin; serious adverse events were documented in 4.5%, 1.2%, and 3.6% of patients, respectively. Incidence of weight gain and edema were low but relatively more common in patients treated with chiglitazar 48 mg compared with chiglitazar 32 mg or sitagliptin.
“In conclusion, chiglitazar showed non-inferior effect compared with sitagliptin on HbA1c reduction with well tolerated safety profile,” wrote the researchers.
One author disclosed associations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
Jia W, Ma J, Miao H, et al. Efficacy and safety of chiglitazar vs. sitagliptin in patients with type 2 diabetes: a 24-week, randomized, double-blind, noninferiority phase 3 Trial (CMAS). Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, California. Oral Presentation 18-OR.