Background: The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA).
Methods: We conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999-2012) and a commercial health insurance plan (Optum Clinformatics | 2000-2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset.
Results: The adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75-1.10) in Medicaid and 0.88 (0.61-1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54-0.93] and 1.16 [0.89-1.52] in men and women respectively, interaction term p-value = 0.01).
Conclusions: Rosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041286 | PMC |
http://dx.doi.org/10.1186/s12933-020-00999-5 | DOI Listing |
Metabolomics
December 2024
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
J Cell Mol Med
December 2024
Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
Naunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Pharmacy, School of Health Sciences, Central University of South Bihar, Gaya, 824236, India.
Thiazolidinedione derivatives have shown significant potential as targeted cancer therapies by leveraging their various mechanisms of action. These include suppressing cell proliferation, triggering apoptosis, and influencing signaling pathways associated with tumor development. Their multifaceted effects make them promising candidates for advancing cancer treatment strategies.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
November 2024
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, Maharashtra, 400019, India.
Polycystic ovarian syndrome (PCOS) is one of the chief causes of infertility in women of reproductive age. Several drugs belonging to the oral contraceptive class have been approved for the treatment of PCOS. Nonetheless, the capability to target only a few symptoms of PCOS and fatal side effects are key hurdles to their use.
View Article and Find Full Text PDFMolecules
October 2024
School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Thiazolidinediones (TZDs) including rosiglitazone and pioglitazone function as peroxisome proliferator-activated receptor gamma (PPARγ) full agonists, which have been known as a class to be among the most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, side effects of TZDs such as fluid retention and weight gain are associated with their full agonistic activities toward PPARγ induced by the AF-2 helix-involved "locked" mechanism. Thereby, this study aimed to obtain novel PPARγ partial agonists without direct interaction with the AF-2 helix.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!