New injection makes fat cells self-destruct

The drug, known as CBL-514, was highlighted at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy. Research indicates that it can reduce both subcutaneous fat, which sits directly beneath the skin, and visceral fat, which surrounds internal organs.

Dr. W. Timothy Garvey of the University of Alabama at Birmingham says the findings also raise the possibility that CBL-514 could reduce weight regain after patients discontinue GLP-1 receptor agonist medications (GLP1-RAs) like Ozempic, Wegovy, Mounjaro, and Zepbound. However, this potential benefit has so far been demonstrated in animal studies and still needs to be confirmed in humans.

A New Injection That Makes Fat Cells Self-Destruct

What makes CBL-514 unusual is how it works. Rather than simply reducing the amount of fat stored inside existing cells, the drug triggers apoptosis (self-destruction), a natural biological process that causes cells to break down and die. CBL-514 is designed to target adipocytes, the body's fat-storing cells, while leaving other types of cells unaffected.

In phase 2 clinical trials, researchers observed substantial reductions in subcutaneous fat. This is the soft layer of fat immediately below the skin that can be "pinched."

At the eight-week follow-up, 69.6% of participants treated with CBL-514 had lost at least 150 mL of subcutaneous fat volume. None of the participants who received a placebo reached that threshold.

Animal experiments provided additional evidence that the treatment could affect more than just visible body fat. In preclinical studies (animal models), CBL-514 reduced body weight as well as subcutaneous and visceral abdominal tissue (VAT).

Visceral fat is especially important from a medical perspective. Unlike fat that accumulates directly beneath the skin, visceral fat lies deep within the abdominal cavity, surrounding organs such as the liver and intestines.

This hidden fat is biologically active and can interfere with the body's ability to regulate blood sugar and metabolism. Excess visceral fat is a major contributor to insulin resistance, type 2 diabetes, and cardiometabolic conditions, including heart attacks and strokes.

Could the Drug Help Prevent Weight Regain?

One of the most intriguing possibilities involves combining CBL-514 with existing weight loss medications.

GLP-1 receptor agonist drugs have transformed obesity treatment by helping patients lose substantial amounts of weight. However, maintaining those results can be challenging. Many people regain weight after discontinuing treatment.

Researchers investigated whether destroying fat cells could help address this problem.

In animal studies, combining CBL-514 with tirzepatide, a medication used to treat obesity and type 2 diabetes, produced greater weight loss than treatment with tirzepatide alone.

The researchers also examined what happened after tirzepatide was discontinued. Rats that had received both medications regained less weight than rats treated only with tirzepatide.

One possible explanation is that eliminating fat cells reduces the body's capacity to store fat again. With fewer fat cells available, the researchers hypothesize that fat may accumulate more slowly after weight loss.

Professor Garvey believes this approach could eventually help patients preserve the health improvements associated with losing weight, including better blood pressure, blood sugar, and cholesterol levels.

However, whether CBL-514 can reliably prevent weight regain in people remains an open question. Additional clinical research will be needed to determine if the effects observed in animals also occur in humans.

Human Trials Reveal a Reduction in Dangerous Visceral Fat

To investigate the drug's effects on visceral fat in people, Professor Garvey and Yu-Fang Ling of Caliway Biopharmaceuticals, the drug's developer based in New Taipei City, Taiwan, analyzed data from two phase 2 clinical trials (CBL-0204 and CBL-0205).

The analysis focused on participants who had undergone magnetic resonance imaging, or MRI, allowing researchers to measure changes in fat deep inside the abdomen.

Participants (BMI 22-30 kg/m2) received injections into the lower abdomen every three weeks for up to 12 weeks. The treatment involved doses of up to 600 mg of CBL-514 (n=23) or placebo (n=17), with participants ranging in average age from 36.4 years to 42.4 years across the groups.

The number of injections depended on how much abdominal fat each participant had. As the fat layer became thinner, fewer injections were administered. Treatment ended once the fat thickness fell below a specified threshold.

MRI scans were performed before treatment and again four weeks and eight to 12 weeks after the final injection. These scans allowed the researchers to compare changes in visceral fat volume between the treatment and placebo groups.

The original subgroup included 41 participants, with 23 assigned to CBL-514 and 18 to placebo. Of those receiving the experimental drug, 17 were women (74%), and six were men (26%). The placebo group included 10 women (56%) and eight men (44.4%).

At the later follow-up, data were available for 40 participants, including all 23 CBL-514 recipients and 17 placebo recipients.

Before treatment, average visceral fat volume was 563.85 mL in the CBL-514 group and 659.81 mL in the placebo group.

Over the following weeks, the two groups showed distinctly different patterns. Visceral fat decreased among participants receiving the experimental injection but increased among those given the placebo.

Hidden Belly Fat Fell by More Than 10%

Four weeks after the final injection, participants treated with CBL-514 had experienced an average 12.01% reduction in visceral fat volume compared with their starting measurements.

In contrast, the placebo group showed an average increase of 5.68%. This represented a 17.69 percentage point difference between the groups.

The results remained encouraging at the later follow-up, conducted eight weeks after the final treatment in CBL-0205 and 12 weeks after treatment in CBL-0204.

By that point, average visceral fat volume in the CBL-514 group was still 10.45% below baseline. Meanwhile, the placebo group had experienced an average increase of 11.76%.

That produced a difference of 22.21 percentage points between the two groups, suggesting that the injection's effects persisted for several weeks after treatment ended.

The researchers concluded that CBL-514 significantly reduced visceral abdominal fat compared with placebo. Combined with the earlier findings on subcutaneous fat, the results suggest that the treatment can target both fat beneath the skin and fat surrounding internal organs.

The drug was also generally well tolerated during the trials. Most reported side effects involved temporary reactions around the injection site, including pain, swelling, and redness. These reactions were generally mild to moderate, and no serious adverse events were reported.

Beyond a Flatter Stomach: Potential Health Benefits

Although reducing visible belly fat may appeal to patients for cosmetic reasons, researchers emphasize that the potential medical benefits could be more important.

Professor Garvey says: "We expect that patients will be pleased by the cosmetic effects, such as the flatter stomach that can come with subcutaneous fat loss. 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."

Because visceral fat is closely linked to metabolic disease, reducing it could potentially provide benefits beyond changes in appearance.

The researchers also point out that existing surgical approaches, including liposuction and abdominoplasty, primarily remove or reshape subcutaneous fat. These procedures are more invasive and do not directly address the deeper visceral fat surrounding abdominal organs.

CBL-514 could potentially offer a nonsurgical alternative that targets both types of abdominal fat.

"This is a highly innovative approach to obesity pharmacotherapy that has produced some remarkable results in early human trials," says Professor Garvey.

Larger Clinical Trials Will Test the Treatment

Despite the promising findings, CBL-514 remains an experimental treatment, and larger studies are needed to establish its effectiveness and safety.

Recruitment for the first of two phase 3 clinical trials was underway at the time of the announcement. Both studies are designed as randomized, placebo-controlled trials that will investigate whether CBL-514 can safely and effectively reduce abdominal fat without surgery.

The announcement indicated that initial results were expected at the end of the following year.

These larger trials will be important for determining whether the encouraging reductions in abdominal fat observed in early studies can be reproduced in broader patient populations.

Researchers will also need to establish whether reducing fat cell numbers produces lasting improvements in weight management and metabolic health, particularly after patients stop taking GLP-1 medications.

If the findings hold up, CBL-514 could represent a different strategy for obesity treatment, one focused on eliminating fat cells rather than simply reducing the amount of fat they contain.