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

Diabetes Obes Metab. 2025 Nov;27(11):6243-6253. doi: 10.1111/dom.70009. Epub 2025 Aug 22.

Abstract

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).

Keywords: chiglitazar; haemoglobin; metformin; peroxisome proliferator‐activated receptor; type 2 diabetes mellitus.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Male
  • Metformin* / administration & dosage
  • Metformin* / adverse effects
  • Metformin* / therapeutic use
  • Middle Aged
  • Treatment Outcome

Substances

  • Metformin
  • Hypoglycemic Agents
  • Glycated Hemoglobin
  • Blood Glucose
  • hemoglobin A1c protein, human

Associated data

  • ClinicalTrials.gov/NCT04807348