CBL-514 is a first-in-class small-molecule injectable drug developed by Caliway Biopharmaceuticals. It acts as a lipolysis agent that induces adipocyte apoptosis (programmed cell death). While primarily investigated for aesthetic localized fat reduction and rare adipose disorders (Dercum’s disease), recent data suggests it may offer systemic metabolic benefits when combined with GLP-1 receptor agonists, specifically by targeting visceral fat and preventing weight rebound.
Current Status: Investigational (Phase 2b/3). Not FDA-approved for general use.
While initial studies focused on subcutaneous fat (aesthetic), the most compelling evidence for healthspan lies in its recent combination trials with GLP-1 receptor agonists (e.g., tirzepatide/Zepbound).
- Visceral Fat Reduction: In preclinical models presented at EASD 2025, CBL-514 combined with GLP-1 therapy reduced visceral fat by 367.4% more than GLP-1 monotherapy alone. Visceral fat is highly metabolically active and directly linked to insulin resistance, cardiovascular disease, and reduced longevity.
- Prevention of Weight Rebound: A major limitation of GLP-1 drugs is rapid weight regain upon cessation. CBL-514 appears to mitigate this by permanently removing adipocytes, thus removing the “sink” for energy storage during the rebound phase.
- Phase 2 IND (CBL-0201WR): The FDA has cleared a Phase 2 study specifically to evaluate CBL-514 + tirzepatide for weight management, measuring body composition and metabolic indicators.
| Benefit Category | Evidence Strength | Mechanism | Relevance to Longevity |
|---|---|---|---|
| Local Fat Reduction | High (Phase 2b) | Adipocyte Apoptosis | Low (Cosmetic/Psychological) |
| Dercum’s Disease | High (Phase 2) | Lipoma Clearance | Moderate (Quality of Life/Inflammation) |
| Visceral Fat Loss | Moderate(Preclinical) | GLP-1 Synergy | High (Metabolic Risk Reduction) |
| Rebound Prevention | Moderate(Preclinical) | Hyperplasia Reduction | High (Sustainable Weight Management) |
Mechanism of Action: Apoptosis vs. Necrosis
CBL-514 is distinct from earlier lipolytic agents (e.g., deoxycholic acid) which typically cause adipocyte necrosis—a messy cell death triggering inflammation and tissue damage.
- DYRK1b Inhibition: Preclinical studies suggest CBL-514 inhibits the cell survival kinase DYRK1b.
- Apoptotic Cascade: This inhibition upregulates caspase-3 and the Bax/Bcl-2 ratio, triggering the mitochondrial apoptotic pathway.
- Result: The targeted fat cells shrink and die in a controlled manner, and are cleared by macrophages without significant necrosis or collateral damage to nerves or skin.
Clinical Relevance: By reducing the absolute number of fat cells (hyperplasia reduction) rather than just their size (hypertrophy reduction), CBL-514 theoretically lowers the “metabolic memory” of adipose tissue, reducing the likelihood of rapid fat regain.
More information:
The Company Website: Caliway Biopharmaceuticals Co., Ltd | Development of new drugs for aesthetic medicine and chronic inflammation.