Pharmacological mechanisms of injectable adipose reduction: a paradigm shift from nonselective cytolysis to targeted adipocyte apoptosis and metabolic modulation

The demand for minimally invasive approaches to reduce localized adipose tissue has increased with the expansion of aesthetic medicine. To construct this review, a structured literature search (1990–2026) was conducted across PubMed, Scopus, and Web of Science. While injectable adipose reduction therapies have been used clinically for decades, their pharmacological mechanisms remain incompletely understood from an adipocyte biology perspective. Notably, it is critical to explicitly distinguish preclinical in vitro/in vivo evidence from human clinical trial data when evaluating these agents. Classical cytolytic agents, such as deoxycholic acid, reduce adipose tissue mainly through detergent-mediated membrane disruption and necrotic adipocyte death. Although these agents are strongly clinically validated, their efficacy relies on nonspecific membrane injury, local inflammation, and limited cellular selectivity. In contrast, metabolic and signaling-based agents (e.g., β-adrenergic agonists, phosphodiesterase inhibitors, and AMPK modulators) primarily regulate lipid mobilization and fatty acid oxidation without directly eliminating adipocytes. However, evidence supporting durable localized fat reduction with these approaches remains limited. Recent injectable agents represent a paradigm shift toward mechanism-defined adipocyte elimination. Preclinical evidence supporting the use of purified phosphatidylcholine-based formulations (e.g., AYP-101) suggests that purified phosphatidylcholine induces TLR4-associated NF-κB–TNF-α signaling, driving downstream lipolytic and apoptotic responses. Moreover, clinical reports of CBL-514 describe a proposed DYRK1B-linked apoptosis-oriented mechanism involving Bax/Bcl-2 regulation. Alternatively, RZL-012 represents a distinct liponecrotic approach involving direct membrane injury and inflammatory clearance. While apoptosis-oriented approaches may enable regulated adipocyte elimination, their comparative tissue selectivity requires further clinical validation. Furthermore, RNA-based interventions and adipose-targeted delivery systems are emerging as strategies to precisely regulate adipogenic and inflammatory pathways. This review critically compares major injectable strategies in terms of their pharmacological mechanisms, limitations, and translational potential. By reframing the field from simple fat volume reduction toward the regulation of adipocyte fate, lipid handling, and inflammatory remodeling, this framework supports the development of safer, mechanism-based therapies. Ultimately, these approaches may extend beyond aesthetic applications to the therapeutic modulation of dysfunctional adipose tissue in obesity. •Injectable adipose-reduction therapies differentially regulate adipocyte fate and tissue remodeling. •Detergent-based agents induce membrane disruption, necrosis, lipid release, and inflammation. •Metabolic modulators regulate lipid mobilization, oxidation, and fatty acid utilization. •Emerging agents encompass apoptosis-oriented and liponecrotic modes of adipocyte elimination. •Molecular targeting may improve tissue selectivity and support more precise adipose remodeling.