Meta-Analysis
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2023; 14(10): 1573-1584
Published online Oct 15, 2023. doi: 10.4239/wjd.v14.i10.1573
Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes: A meta-analysis
Chu Lin, Zong-Lin Li, Xiao-Ling Cai, Sui-Yuan Hu, Fang Lv, Wen-Jia Yang, Li-Nong Ji
Chu Lin, Zong-Lin Li, Xiao-Ling Cai, Sui-Yuan Hu, Fang Lv, Wen-Jia Yang, Li-Nong Ji, Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China
Author contributions: Ji LN and Cai XL were responsible for the study concept and designed the systematic review protocol; Lin C and Li ZL performed the study selection and data extraction; Lin C and Li ZL performed the statistical analyses; Lin C, Li ZL and Cai XL prepared the outlines and wrote the manuscript; All authors contributed to the critical revision of manuscript drafts.
Supported by Beijing Natural Science Foundation, No. 7202216; National Natural Science Foundation of China, No. 81970698 and No. 81970708.
Conflict-of-interest statement: LJ has received fees for lecture presentations and for consulting from AstraZeneca, Merck, Metabasis, MSD, Novartis, Eli Lilly, Roche, Sanofi-Aventis and Takeda. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare. No other support from any organization for the submitted work other than that described above.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Nong Ji, MD, Professor, Department of Endocrinology and Metabolism, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. jiln@bjmu.edu.cn
Received: June 8, 2023
Peer-review started: June 8, 2023
First decision: July 18, 2023
Revised: July 22, 2023
Accepted: August 17, 2023
Article in press: August 17, 2023
Published online: October 15, 2023
Processing time: 123 Days and 5.3 Hours
Abstract
BACKGROUND

Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors (PPAR)-α, δ and γ, 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-γ 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 chig-litazar 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-β (HOMA-β) (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/m2 or diabetes duration < 10 years, the HbA1c reduction and HOMA-β 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 β-cell function preserving capacity, and does not increase the risk of safety concerns when compared with TZD.

Keywords: Chiglitazar; Thiazolidinedione; Glycemic control; β-cell function; Drug safety

Core Tip: This is the first indirect meta-analysis comparing efficacy and safety of chiglitazar and thiazolidinediones (TZDs). In patients with type 2 diabetes, compared with TZDs, chiglitazar induced favorable glycemic and lipidemic control, preserved β-cell function, without increasing safety concerns.