People on an unapproved weight-loss jab report a very ironic side effect

It's been called the next big weight-loss jab. It isn't approved. And thousands of people online say they're injecting it anyway.

Now researchers have combed through what those users are posting, and the most common complaint is an odd one for a drug built to curb appetite.

They're hungrier.

Increased appetite was the most frequently reported symptom among people who said they were taking retatrutide, according to a University of Pennsylvania study published October 14 in JAMA Network Open.

A triple-action jab

Retatrutide is an experimental drug in the same family as Ozempic and Mounjaro, developed by Eli Lilly. It is still in Phase 3 trials.

Semaglutide, the drug in Ozempic, acts on one hormone receptor and tirzepatide, in Mounjaro, on two. Retatrutide acts on three.

Trial results released in late September made headlines. TODAY reported that people without diabetes lost up to 25% of their body weight.

Outside trials, people buy it from unregulated online sellers. The FDA has sent 21 warning letters to retatrutide sellers since December 2024 and warns against buying it, including products labeled for research, according to Magica.

What 150,000 posts said

The Penn team used AI to analyze 148,640 Reddit posts and comments from 38,936 users across 27 communities, from May 2021 to December 2025.

Of those, 13,589 users said they were currently taking retatrutide. After leaving out expected effects like weight loss and a smaller appetite, 7,823 reported at least one symptom.

Increased appetite topped the list at 17.1%. Then came fatigue (15.2%), more energy (12.4%), nausea (11.6%), food cravings (7.3%), insomnia (6.1%) and a faster heart rate (4.8%).

That's a different picture from Phase 2 trials, which mainly reported stomach trouble such as nausea.

Compared with the team's earlier Reddit research on semaglutide and tirzepatide, retatrutide users talked proportionally more about appetite, sleep, heart rate and muscles.

"AI makes it possible to analyze these conversations at scale," said first author Neil Sehgal, a Penn doctoral student.

Nobody knows what's in the vial

The researchers are blunt about the limits. "We can't say that retatrutide is causing these symptoms," said co-author Lyle Ungar.

Reddit users aren't trial participants, and there's no way to check whether they took real retatrutide. Gray-market products can differ in ingredients, purity and dose, and some users take several peptides at once.

Magica reports a University of Queensland test of three products labeled 10 mg found between half and about 1.67 times that amount. Australia's regulator found one product sold as retatrutide contained semaglutide and no retatrutide at all.

"Our goal is to identify hypotheses in online conversations that we could test," said senior author Sharath Chandra Guntuku.

The authors call the findings hypothesis-generating. They want clinicians to ask patients, without judgment, about unapproved peptide use and to report side effects to the FDA's MedWatch system. Tronieri disclosed a grant from Novo Nordisk and consulting fees from Currax Pharmaceuticals.