Historically, such behavioral complexity was viewed as a disqualifying feature for drug development, as CNS-acting agents were associated with unpredictable neuropsychiatric liability and high regulatory barriers (Bray and Greenway, 2007
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Abbreviations ADA: Adenosine deaminase ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Afib: Atrial fibrillation BNP: Brain natriuretic peptide cAMP: Cyclic adenosine 3,5-monophosphate CI: Confidence interval CKD: Chronic kidney disease CVD: Cardiovascular disease CVOTs: Cardiovascular outcome trials DPP-4: Dipeptidyl peptidase-4 DPP-4i: DPP-4 inhibitor eGFR: Estimated glomerular filtration rate FDA: Food and Drug Administration GAS: Interferon-gamma-activated sequence GIP: Glucose-dependent insulinotropic polypeptide GLP-1: Glucagon-like peptide-1 GLP-1R: GLP-1 receptor GLP-1RAs: Glucagon-like peptide-1 receptor agonists HbA1c: Glycated hemoglobin HDL: High-density lipoprotein HF: Heart failure HNF-1: Hepatocyte nuclear factor-1 HR: Hazard ratio hs-CRP: High-sensitivity C-reactive protein IL-12: Interleukin-12 IVUS: Intravascular ultrasound LDL: Low-density lipoprotein LVEF: Left ventricular ejection fraction MACE: Major adverse cardiovascular events MI: Myocardial infarction MMPs: Matrix metalloproteases PAI-1: Plasminogen activator inhibitor-1 PCI: Percutaneous coronary intervention PKA: Protein kinase A PWV: Pulse wave velocity SGLT-2i: Sodium/glucose cotransporter-2 inhibitors STAT1: Signal transducer and activator of transcription 1 T1DM: Type 1 diabetes mellitus T2DM: Type 2 diabetes mellitus TGF-: Transforming growth factor- TLR4: Toll-like receptor 4 TNF-: Tumor necrosis factor- TRIF: TIR-domain-containing adapter-inducing interferon- UKPDS: United Kingdom Prospective Diabetes Study VLDL: Very low-density lipoprotein References Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, et al

Advancing Drug Safety in Drug Development: Bridging Computational Predictions for Enhanced Toxicity Prediction