Chiglitazar Sodium

Diabetes mellitus is a prevalent metabolic disorder characterized by impaired glucose metabolism. This study investigates the anti-diabetic potential of Cotula cinerea essential oil (EO) through in vivo, in vitro, and computational methodologies. In vitro enzyme inhibition assays demonstrated that C. cinerea EO effectively inhibits α-amylase and α-glucosidase, indicating its potential role in glucose regulation. In vivo studies further confirmed its hypoglycemic effects. GC-MS analysis identified 31 bioactive compounds within the EO. Molecular docking studies revealed that six of these compounds exhibited strong binding affinities to α-amylase and α-glucosidase, comparable to those of the standard drug acarbose (ARE). Among them, cis-verbenyl acetate (CVA) and β-terpineol (βTP) showed the highest docking scores against both enzymes. ADMET analysis confirmed their favorable pharmacokinetic properties, drug-likeness, and low toxicity risks. Molecular dynamics simulations demonstrated the stable binding of CVA and βTP with both enzymes, exhibiting lower RMSD and RMSF values compared to ARE, along with favorable Rg and SASA parameters. MM-PBSA calculations further validated their strong binding affinities. Density Functional Theory calculations provided deeper insights into the electronic characteristics of CVA and βTP, revealing their frontier molecular orbitals distributions and energy gap (∆E) values. The molecular electrostatic potential analysis identified key electron-rich and electron-deficient regions, suggesting potential interaction sites with the target enzymes. The observed reduction in ∆E values under aqueous conditions indicated increased molecular stability and reactivity within physiological environments, further supporting their role in enzyme inhibition. Overall, this study highlights C. cinerea EO as a promising natural source for diabetes management. The integration of in vivo, in vitro, and computational approaches offers compelling evidence for its therapeutic potential. Nevertheless, further experimental validation is necessary to assess its clinical applicability.

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).

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.

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.

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).