Can A New Injection Prevent Weight Regain After Ozempic? Early Trials Show Promise

An experimental injection that prompts fat cells to destroy themselves has delivered encouraging results in early human trials, notably cutting dangerous fat hidden deep within the abdomen. Researchers say the treatment could one day offer a fresh approach to obesity and might help people keep the weight off after they stop popular weight loss medications.

The drug, known as CBL-514, was presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy. Findings so far indicate it can shrink two kinds of fat: subcutaneous fat, which lies directly beneath the skin, and visceral fat, which surrounds internal organs.

A Different Way to Target Fat

CBL-514 stands apart because of its mechanism. Instead of simply draining the fat stored inside existing cells, it triggers apoptosis, a natural process in which cells break down and die. The drug is designed to home in on adipocytes, the body’s fat-storing cells, while sparing other cell types.

What the Phase 2 Trials Found

Phase 2 participants showed substantial losses of subcutaneous fat, the soft layer that can be “pinched.” At the eight-week follow-up, 69.6% of those treated with CBL-514 had lost at least 150 mL of subcutaneous fat volume. No participant on placebo reached that level.

Animal experiments hinted at wider effects. In preclinical models, CBL-514 lowered body weight and reduced both subcutaneous and visceral abdominal tissue (VAT).

Why Visceral Fat Is the Bigger Concern

From a medical standpoint, visceral fat is the more worrying type. It sits deep in the abdominal cavity, wrapped around organs such as the liver and intestines. This tissue is biologically active and can disrupt how the body regulates blood sugar and metabolism. Too much of it is a leading driver of insulin resistance, type 2 diabetes and cardiometabolic problems, including heart attacks and strokes.

Could It Help Stop Weight Regain?

One of the most intriguing prospects is pairing CBL-514 with current weight loss drugs. GLP-1 receptor agonists (GLP1-RAs) such as Ozempic, Wegovy, Mounjaro and Zepbound have transformed obesity care by helping patients lose substantial weight. Keeping it off is harder, though, and many people regain weight once treatment ends.

To see whether eliminating fat cells could address that problem, researchers turned to animal studies. Combining CBL-514 with tirzepatide, a medication used for obesity and type 2 diabetes, produced greater weight loss than tirzepatide alone. After tirzepatide was stopped, rats that had received both drugs regained less weight than rats given tirzepatide only.

The researchers’ working explanation is that fewer fat cells means less capacity to store fat again, so fat may build up more slowly after weight loss.

Dr. W. Timothy Garvey of the University of Alabama at Birmingham says the findings raise the possibility that CBL-514 could reduce weight regain after patients discontinue GLP-1 medications. He also believes the approach could eventually help people hold on to the health gains that come with weight loss, including better blood pressure, blood sugar and cholesterol levels. That benefit has so far been shown only in animals and still needs to be confirmed in humans.