Comparison of Cholic Acid (MT921) and Deoxycholic Acid (DCA) in Fat Reduction Efficacy and Skin Adverse Reactions in...

Background/Objectives: This study compared fat reduction efficacy of cholic acid-based formulation (MT921) and deoxycholic acid (DCA), as well as skin adverse reactions (ADR), in mini pigs, mice, and rats. DCA is the active pharmaceutical ingredient found in several fat-dissolving injectables, such as Kybella^®, V-OLET^®, and Bellacholine^®. Methods: In one study, single subcutaneous (s.c.) injections of 1.5% MT921 and 1% DCA were administered to the back of a mini pig at different sites and time points to ascertain histopathological events. In another study, three mini pigs received six repeated s.c. injections of 1.5% MT921 and 1% DCA at 4-week intervals, and changes in subcutaneous fat volume were monitored by magnetic resonance imaging (MRI), along with visual examination for ADRs. Additional ADRs were assessed in rodents, such as ulcerative dermatitis (UD) following MT921 and DCA s.c. injections in ICR/CD1 mice, and footpad edema after intraplantar injections in SD rats. Results: In mini pigs, 1.5% MT921 and 1% DCA induced comparable localized fat necrosis, accompanied by inflammatory cell influx and fibrosis. Also, repeated injections of 1.5% MT921 and 1% DCA induced comparable fat volume reduction in outer subcutaneous layer, though changes in middle subcutaneous layer was unaffected. Notably, MT921 evoked milder ADR based on lower incidence of hematoma and absence of nodules in mini pigs, less severe UD in mice, and reduced edema in rats. Conclusions: Local injections of 1.5% MT921 demonstrated fat-reduction efficacy comparable to 1% DCA while eliciting fewer and milder ADRs, supporting MT921 as a promising alternative lipolytic agent.