Efficacy and safety of chiglitazar add‐on to metformin in type 2 diabetes mellitus ( RECAM study)

AIMS: Chiglitazar is a novel peroxisome proliferator-activated receptor pan-agonist regulating glucose and lipid metabolism. The RECAM study aimed to evaluate the efficacy and safety of chiglitazar add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In this randomised, double-blind, phase III trial (NCT04807348), 533 patients with T2DM inadequately controlled by metformin were randomly assigned in a 1:1:1 ratio to receive chiglitazar 32 mg (n = 178), chiglitazar 48 mg (n = 177), or placebo (n = 178) for 24 weeks, in addition to metformin. The primary endpoint was the change in glycosylated haemoglobin (HbA1c) from baseline to week 24. RESULTS: At week 24, the least squares mean changes in HbA1c were -0.91% (95% CI: -1.03% to -0.79%) in the chiglitazar 32 mg group, -1.14% (95% CI: -1.26% to -1.02%) in the chiglitazar 48 mg group, and -0.49% (95% CI: -0.62% to -0.36%) in the placebo group. Both chiglitazar 32 mg and 48 mg significantly reduced HbA1c compared to placebo (both p < 0.001), with the reduction being greater in the 48 mg group than in the 32 mg group (p = 0.008). Chiglitazar significantly improved fasting plasma glucose and 2-h postprandial glucose while reducing triglyceride and free fatty acid levels and increasing high-density lipoprotein cholesterol levels. The incidence of adverse events was comparable across groups, with a slight increase in weight gain and mild oedema observed in the chiglitazar groups. CONCLUSIONS: Chiglitazar combined with metformin significantly improves glycaemic control and lipid metabolism in Chinese patients with T2DM who are inadequately managed with metformin and have a favourable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04807348).