Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

Wang, Xingyue; Wang, You; Hou, Junjie; Liu, Hongyang; Zeng, Rong; Li, Xiangyu; Han, Mei; Li, Qingrun; Ji, Linong; Pan, Desi; Jia, Weiping; Zhong, Wen; Xu, Tao

doi:10.1038/s41598-024-51210-8

Cited by 2 publications

(1 citation statement)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from PPAR dual agonist, a pan-PPAR agonist targeting PPAR alpha/delta/gamma has been developed and recently approved for use in patients with T2DM and non-alcoholic steatohepatitis in China [210]. In a phase III trial, chiglitazar significantly improved insulin sensitivity and HOMA-IR compared to placebo or sitagliptin over 24 weeks of treatment [211].…”

Section: Dual Peroxisome Proliferator-activated Receptor (Pparα/γ) Ag...mentioning

confidence: 99%

Novel Therapeutics for Type 2 Diabetes Mellitus—A Look at the Past Decade and a Glimpse into the Future

Chee,

Dalan

2024

Biomedicines

View full text Add to dashboard Cite

Cardiovascular disease (CVD) and kidney disease are the main causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Globally, the incidence of T2DM continues to rise. A substantial increase in the burden of CVD and renal disease, alongside the socioeconomic implications, would be anticipated. Adopting a purely glucose-centric approach focusing only on glycemic targets is no longer adequate to mitigate the cardiovascular risks in T2DM. In the past decade, significant advancement has been achieved in expanding the pharmaceutical options for T2DM, with novel agents such as the sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide receptor agonists (GLP-1 RAs) demonstrating robust evidence in cardiorenal protection. Combinatorial approaches comprising multiple pharmacotherapies combined in a single agent are an emerging and promising way to not only enhance patient adherence and improve glycemic control but also to achieve the potential synergistic effects for greater cardiorenal protection. In this review, we provide an update on the novel antidiabetic agents in the past decade, with an appraisal of the mechanisms contributing to cardiorenal protection. Additionally, we offer a glimpse into the landscape of T2DM management in the near future by providing a comprehensive summary of upcoming agents in early-phase trials.

show abstract

Section: Dual Peroxisome Proliferator-activated Receptor (Pparα/γ) Ag...mentioning

confidence: 99%

Novel Therapeutics for Type 2 Diabetes Mellitus—A Look at the Past Decade and a Glimpse into the Future

Chee,

Dalan

2024

Biomedicines

View full text Add to dashboard Cite

show abstract

A mendelian randomisation study of the causal effect of exercise intensity on the development of type 2 diabetes

Yu,

Bi,

Qian

et al. 2024

Front. Physiol.

View full text Add to dashboard Cite

ObjectiveThis study examines the causal effects of varying exercise intensities on type 2 diabetes mellitus (T2D) through Mendelian randomization (MR) analysis, using genetic variants as instrumental variables.MethodsA two-sample MR analysis was performed, employing Inverse Variance Weighted (IVW) as the primary method, supported by weighted median, MR-Egger regression, MR-PRESSO, and MR robustness-adjusted contour scores. Data were obtained from the International Exercise Genetics Database (IEGD) and the Global Diabetes Research Consortium (GRC), encompassing over 150,000 individuals for exercise intensity and around 200,000 T2D patients and controls. SNPs linked to exercise intensity were selected based on genome-wide significance (P < 5 × 10^-8) and linkage disequilibrium criteria (distance >10,000 kb, r^2 < 0.001).ResultsThe IVW analysis suggested that high-intensity exercise might reduce T2D risk, but the association was not statistically significant (OR = 0.667, 95% CI = 0.104–4.255, P = 0.667). The wide confidence interval indicates uncertainty in the effect estimate. Low-intensity exercise showed no significant effect on T2D risk (OR ∼ 1.0). Sensitivity analyses, including weighted median and MR-Egger regression, confirmed no significant association between high-intensity exercise and T2D risk. The MR-PRESSO analysis found no significant outliers, and the global test for pleiotropy was non-significant (P = 0.455). Cochran’s Q test for heterogeneity in the IVW analysis was non-significant (Q = 12.45, P = 0.234), indicating consistency among SNP-derived estimates.ConclusionHigh-intensity exercise potentially reduces T2D risk, but the association is not statistically significant. Further research is needed to understand the complex relationship between exercise intensity and T2D.

show abstract

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

Cited by 2 publications

References 70 publications

Novel Therapeutics for Type 2 Diabetes Mellitus—A Look at the Past Decade and a Glimpse into the Future

Novel Therapeutics for Type 2 Diabetes Mellitus—A Look at the Past Decade and a Glimpse into the Future

A mendelian randomisation study of the causal effect of exercise intensity on the development of type 2 diabetes

Contact Info

Product

Resources

About