Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes: A meta-analysis

BACKGROUND Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors (PPAR)-alpha, delta and gamma, and has therapeutic potential for type 2 diabetes (T2D). However, to date, no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-gamma agonist thiazolidinediones (TZDs). A meta-analysis concerning this topic is therefore required. AIM To compare the efficacy and safety of chiglitazar and TZD in patients with T2D. METHODS PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022. Randomized controlled trials (RCTs) of chiglitazar or TZD vs placebo in patients with T2D were included. Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest. RESULTS We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo. For efficacy endpoints, the augmented dose of chiglitazar resulted in greater reductions in hemoglobin (Hb)A1c [weighted mean difference (WMD) = -0.15%, 95% confidence interval ( CI): -0.27 to -0.04%], triglycerides (WMD = - 0.17 mmol/L, 95%CI: -0.24 to - 0.11 mmol/L) and alanine aminotransferase (WMD = - 5.25 U/L, 95% CI: - 8.50 to - 1.99 U/L), and a greater increase in homeostasis model assessment-beta (HOMA-beta) (WMD = 17.75, 95%CI: 10.73-24.77) when compared with TZD treatment. For safety endpoints, the risks of hypoglycemia, edema, bone fractures, upper respiratory tract infection, urinary tract infection, and weight gain were all comparable between the augmented dose of chiglitazar and TZD. In patients with baseline HbA1c >= 8.5%, body mass index >= 30 kg/m(2) or diabetes duration < 10 years, the HbA1c reduction and HOMA-beta increase were more conspicuous for the augmented dose of chiglitazar compared with TZD. CONCLUSION Augmented dose of chiglitazar, a pan-activator of PPARs, may serve as an antidiabetic agent with preferable glycemic and lipid control, better beta-cell function preserving capacity, and does not increase the risk of safety concerns when compared with TZD.