New Injectable Substantially Reduces Visceral Adipose Tissue in Obesity

CBL-514 has successfully reduced visceral adipose tissue (VAT) in patients with obesity or overweight, according to new readouts from the CBL-0204 and CBL-0205 studies.1,2

In development by Caliway Biopharmaceuticals, CBL-514 is a first-in-class small-molecule injection that specifically and selectively induces adipocyte apoptosis. In both preclinical models and the aforementioned Phase 2 trials, CBL-514, administered either independently or in combination with GLP-1 medications, has demonstrated substantial synergistic reductions in L2-L3 VAT.2

“We expect that patients will be pleased by the cosmetic effects, such as the flatter stomach that can come with subcutaneous fat loss,” W. Timothy Garvey, MD, professor of medicine in the department of nutrition sciences at the University of Alabama at Birmingham, said in a statement. “But it is the reduction in body weight, loss of visceral fat, and the improvements in blood pressure, cholesterol, and the like that should be associated with this that will be important for health.”1

Garvey and colleagues conducted an analysis including patients from the CBL-0204 and CBL-0205 with a body mass index (BMI) of 22-30 kg/m2 and a body weight change of <6.61 lb. Patients with evaluable MRI data were included in the L2-L3 VAT assessment. The team quantified VAT volume from MRI scans via AI-assisted segmentation with predefined anatomical boundaries.2

A total of 46 patients were ultimately included in the analysis. Among the 26 patients receiving CBL-514, baseline VAT volume was 642.5 mL compared to 677.4 mL in the 20-patient placebo group. Garvey and colleagues evaluated changes from baseline at week 4 and weeks 8-12, analyzing absolute and percentage shifts.2

By week 4, mean VAT volume had dropped by 65.5 mL in the CBL-514 arm and increased by 29.4 mL in the placebo arm. The team calculated a treatment difference of -94.9 mL by t-test (P = .0015). A Hodges-Lehmann median difference estimate returned -73.4 mL (P = .0009). Percentage change from baseline was -10.9% in the CBL-514 arm compared to 4.6% with placebo, which corresponded to a treatment difference of -15.5% by t-test (P = .0019) and -12.4% by Wilcoxon test (P = .0008).2

At week 8-12, mean VAT volume decreased by 58.1 mL in the treatment arm and risen by 79.4 mL in the placebo arm, resulting in a treatment difference of -137.5 mL by t-test (P = .0015), while the Hodges-Lehmann estimated difference was -116 mL (P = .0020). Percentage change was -7.3% among patients receiving treatment and 18.4% among those assigned to placebo. Treatment difference was -25.7% by t-test (P = .0309) and -20.2% by Wilcoxon test (P = .0173).2

Garvey and colleagues conducted parametric and non-parametric analyses, confirming that these findings were consistent and supporting CBL-514’s efficacy in this indication. These results are also consistent with previous animal studies, further establishing the drug’s potential metabolic benefits in isolation and with GLP-1 receptor agonists.2

“This is a highly innovative approach to obesity pharmacotherapy that has produced some remarkable results in early human trials,” Garvey said in a statement.1

References

1. European Association for the Study of Diabetes. New weight-loss injection targets fat cells – CBL-514 is designed to reduce levels of subcutaneous and visceral fat. Eurekalert. October 1, 2026. Accessed October 7, 2026. https://www.eurekalert.org/news-releases/1146063

2. Ling Y, Liang M, Garvey T, et al. CBL-514, a first-in-class adipocyte apoptosis-inducing injection, reduces MRI-measured L2-L3 visceral adipose tissue: translational evidence from preclinical models to a Phase 2 clinical trial. Abstract presented at the European Association for the Study of Diabetes (EASD), Milan, Italy. September 28-October 2, 2026.