New research,
explained simply.

In simple words: most fat loss shrinks fat cells, which can fill back up later. CBL-514 is an experimental injection that makes fat cells under the skin switch on their own "self-destruct" program (apoptosis). Your immune cells then quietly clear them away. Because the cells are gone rather than shrunk, researchers think the fat may be less likely to come back, but that hasn't been proven.

What the trials found

• Two phase 2 trials (107 and 173 people) showed it reduced fat under the skin of the belly in most volunteers. In the phase 2b trial, MRI showed abdominal fat volume fell about 20%, and about 77% of people improved by at least one grade on a clinician's fat rating, versus 19% on placebo.
• In a smaller analysis of 41 people, visceral (deep belly) fat fell about 12% after up to 12 weeks, while it rose about 5.7% on placebo. That's an early, exploratory signal, not a confirmed benefit.
• In rats, combining CBL-514 with tirzepatide led to more weight loss and less regain after tirzepatide stopped. That hasn't been tested in people yet.
• Most results so far come from conference presentations and company announcements; the full data still need peer review.

Side effects so far

• Mostly mild to moderate and at the injection site: pain and tenderness (most common, fading over days), swelling, redness and light bruising.
• Local hives at the injection site in about 6% of people in one trial; some stopped early.
• No serious whole-body problems (heart, lungs, brain) reported, and no nerve injury or skin death (necrosis) seen so far, unlike some older fat-dissolving injections. Small, short trials can't rule out rare or delayed harms.

How far is it from FDA approval?

1. ✓Lab and animal studiesDone
2. ✓Phase 1: safety in small groupsDone
3. ✓Phase 2 / 2b: does it work, at what dose?Done: two trials (107 and 173 people) met their goals
4. …Phase 3: large pivotal trialsNow: two global trials (SUPREME-01 and SUPREME-02) cleared by the FDA; first results expected late 2026 to 2027
5. …FDA application (BLA/NDA) and reviewUsually about 10–12 months of review after filing
6. …Approval decisionRealistically 2028 at the earliest, if Phase 3 succeeds

The FDA usually wants two successful large phase 3 trials before approval. If both work and are safe, the company can apply, and review typically takes about a year. And it's being tested for reducing belly fat under the skin (a cosmetic use) first; using it for obesity or visceral fat would need more trials.

Investigational: not an approved weight-loss or cosmetic treatment. Don't use any product sold as CBL-514 outside a regulated clinical trial.

Sources: ScienceAlert, October 2026 · FDA clears second phase 3 trial (2026). The injection-planning sheet shows the trial design only; amounts are set by trial clinicians, and the before-and-after pictures are illustrations, not real patients.

ATX-304 is an oral drug that switches on AMPK, the body's "low fuel" sensor that exercise also turns on. In its first placebo-controlled human trial (23 adults with prediabetes or obesity, 400 mg a day), it lowered liver fat, visceral fat and triglycerides and raised adiponectin, but weight loss was small (about 1.5%) and not significant. A higher-dose trial is next.

Lilly's triple-hormone shot reported up to 25% average weight loss at 80 weeks in TRIUMPH-1, and up to 28.7% in people with knee arthritis (TRIUMPH-4), with big drops in knee pain. Lilly plans to file with the FDA in early 2027. Until then it's not approved anywhere.