An experimental injection that triggers fat cells to self-destruct reduced visceral abdominal fat in early human trials, according to data presented at the European Association for the Study of Diabetes annual meeting in Milan. The drug, CBL-514, is being developed by Caliway Biopharmaceuticals in New Taipei City, Taiwan.

The mechanism is the interesting part. Instead of shrinking the fat already stored inside a cell, CBL-514 is designed to induce apoptosis, the normal process by which a cell breaks itself down and dies, in adipocytes specifically while leaving other cell types alone. The headline claim about weight regain after GLP-1 drugs like Ozempic, Wegovy, Mounjaro and Zepbound rests on rat experiments, not human ones, and the researchers say that still needs confirming in people.

What the MRI data showed

Professor W. Timothy Garvey of the University of Alabama at Birmingham and Yu-Fang Ling of Caliway analyzed MRI subgroups from two phase 2 trials, CBL-0204 and CBL-0205. Participants with a BMI of 22 to 30 received injections into the lower abdomen every three weeks for up to 12 weeks, with 23 on doses up to 600 mg of CBL-514 and 17 on placebo.

Four weeks after the final injection, the treated group averaged a 12.01% reduction in visceral fat volume from baseline while the placebo group averaged a 5.68% increase, a gap of 17.69 percentage points. At the later follow-up the treated group was still 10.45% below baseline against an 11.76% increase on placebo. On subcutaneous fat, 69.6% of treated participants lost at least 150 mL of volume at eight weeks, compared with none of the placebo group.

The regain question

In rats, combining CBL-514 with tirzepatide produced greater weight loss than tirzepatide alone, and the combination animals regained less weight after tirzepatide stopped. The researchers hypothesize that fewer fat cells means less capacity to store fat again, which is a tidy explanation and entirely untested in humans.

Where this sits

Side effects were mostly temporary injection-site pain, swelling and redness, described as mild to moderate, with no serious adverse events reported. These were small subgroups with no long-term data. Recruitment for the first of two randomized, placebo-controlled phase 3 trials was underway at the time of the announcement, with initial results expected at the end of the following year.