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Annual Review of Pharmacology and Toxicology

Volume 65, 2025

Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology

Abstract

Obesity and type 2 diabetes mellitus (T2DM) impact more than 2.5 billion adults worldwide, necessitating innovative therapeutic approaches. Unimolecular polypharmacology, which involves designing single molecules to target multiple receptors or pathways simultaneously, has revolutionized treatment strategies. Blockbuster drugs such as tirzepatide and retatrutide have shown unprecedented success in managing obesity and T2DM, demonstrating superior efficacy compared to conventional single agonists. Tirzepatide, in particular, has garnered tremendous attention for its remarkable effectiveness in promoting weight loss and improving glycemic control, while offering additional cardiovascular and renal benefits. Despite their promises, such therapeutic agents also face challenges that include gastrointestinal side effects, patient compliance issues, and body weight rebound after cessation of the treatment. Nonetheless, the development of these therapies marks a significant leap forward, underscoring the transformative potential of unimolecular polypharmacology in addressing metabolic diseases and paving the way for future innovations in personalized medicine.

Keyword(s): glucagon-like peptide-1 receptor, metabolic diseases, overweight, retatrutide, tirzepatide, unimolecular polypharmacology
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/content/journals/10.1146/annurev-pharmtox-061324-011832
2025-01-23
2025-02-12
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Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology
Annual Review of Pharmacology and Toxicology 65, 191 (2025); https://doi.org/10.1146/annurev-pharmtox-061324-011832
/content/journals/10.1146/annurev-pharmtox-061324-011832
/content/journals/10.1146/annurev-pharmtox-061324-011832
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