Could a new drug that makes fat cells self-destruct be the next big GLP-1?
CBL-514 targets fat cells, and a new study shows that it was effective in slimming down participants’ waistlines.
Early data suggests it’s effective at keeping it off, too.
While GLP-1s mostly decrease fat, they also shed up to 25% vital lean mass. And after stopping GLP-1s, people often regain two thirds of the weight they lost within a year.
“We expect that patients will be pleased by the cosmetic effects, such as the flatter stomach that can come with subcutaneous fat loss,” one author said.
“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.”
Some experts say CBL-514 could turn out to be “a more fundamental obesity therapy” than GLP-1 drugs like Ozempic.
What is CBL-514?
Like many GLP-1s, CBL-514 is an injectable drug. But rather than slowing digestion and decreasing our appetite like GLP-1s do, the new drug works more locally.
It blocks a critical way for fat cells to survive, causing them to die off at the injection site — the belly.
New data from phase 2 clinical trials shows that the drug reduces subcutaneous fat (fat right below the skin) and visceral fat (fat deep inside the body that wraps around the organs). Visceral fat, in particular, is a driver for conditions like diabetes and cardiometabolic issues like heart attack and stroke.
Common surgeries that target subcutaneous fat like liposuction and abdominoplasty (aka a “tummy tuck”) are far more invasive, CBL-514 researchers say. These surgeries also introduce risks far worse than an uneven cosmetic result, including infection, blood vessel blockages, or embolisms, and even an internal organ being punctured.
CBL-514 works on both kinds of fat without the invasive surgery.
“This is a highly innovative approach to obesity pharmacotherapy that has produced some remarkable results in early human trials,” said Dr W. Timothy Garvey, an advisor to Caliway, the drugmaker behind CBL-514, and a professor at University of Alabama at Birmingham.
What the latest data shows
In the latest trials, participants got a shot of CBL-514 every three weeks. The number of shots they got depended on the thickness of their belly fat, which decreased as the drug’s effects took hold.
After just four weeks, average visceral abdominal fat already decreased by 12%. After a total of eight weeks after medication, fat was still 10.45% lower than it was at the start.
Researchers believe that once those fat cells are killed off, the ability for them to grow back is limited, making it difficult to regain the weight.
Right now, CBL-514’s lasting effects after medication is stopped have only been shown in rats, and researchers are looking into whether the effect can be replicated in humans.
Researchers are also exploring whether CBL-514 could work with a GLP-1 drug to help a patient stop taking it while reducing the risk of weight regain.
Other than “mostly mild-to-moderate and transient” injection-site reactions, such as pain, swelling and redness, CBL-514 was generally well tolerated, researchers said. No serious adverse events were reported.
The drug is now entering phase 3 drug trials, the final stage before FDA approval.
