What is GLP-3? The drug behind the next wave of weight-loss medicine

GLP-1 medications have already reshaped how obesity is treated. Now, a new molecule in the pipeline is starting to redefine what’s possible.

In December 2025, Eli Lilly released the first Phase 3 results for retatrutide, a once-weekly injectable that activates three hormone receptors simultaneously: GLP-1, GIP, and glucagon. Online, it’s already being called GLP-3—a nickname, not a medical term, that reflects how quickly the conversation is moving beyond clinical circles.

In the TRIUMPH-4 trial, patients on the highest dose lost an average of 28.7% of their body weight over 68 weeks—roughly 71 pounds. That’s meaningfully beyond what current options like semaglutide and tirzepatide have delivered in trials, and it’s approaching territory previously reserved for surgical intervention.

What the ‘third receptor’ changes

Current GLP-1s work primarily by suppressing appetite and improving blood sugar regulation. Retatrutide adds a glucagon receptor, which works on a different part of the equation entirely. “While GLP-1 and GIP primarily work on the intake side by curbing hunger and improving blood sugar regulation, glucagon activation works on the output side, prompting the body to burn more calories and oxidize fat more efficiently,” says Dr. Rekha Kumar, an endocrinologist and obesity medicine specialist at Weill Cornell Medicine and Senior Medical Advisor at Found. “Think of it as addressing metabolic health from both ends at once.”

The clinical results reflect that. Beyond weight loss, the TRIUMPH-4 data showed meaningful reductions in knee osteoarthritis pain, cardiovascular risk markers, and systemic inflammation. Lilly is running seven additional Phase 3 trials this year across type 2 diabetes, obstructive sleep apnea, metabolic liver disease, and cardiovascular outcomes.

That breadth is the real story. “We made a category error when we called these ‘weight loss drugs,'” says Dr. Jessica Duncan, a board-certified obesity medicine physician and Medical Director at Ivím Health. “What we’re actually looking at is a class of medications that address metabolic dysfunction at a systemic level—and metabolic dysfunction shows up in the liver, in the joints, in the cardiovascular system, in the brain.”

Between the trial and the prescription

It’s important to note that retatrutide is not yet FDA-approved. The Phase 3 results come from a single trial in patients with obesity and knee osteoarthritis, which is a specific population. But the trajectory is consistent.

An earlier trial showed 24.2% weight loss at 48 weeks, with participants still losing weight when the study ended. The Phase 3 numbers went further.

The remaining TRIUMPH readouts expected this year will show how the drug performs across broader and more diverse patient groups, and long-term safety data is still being collected. As Dr. Kumar puts it, “The promise is real; the science just needs to complete its process.” If the data holds, Lilly is expected to file for approval in late 2026, with a decision likely sometime in 2027.

Whether approval translates to access is another question. Current GLP-1 injections cost $1,000 or more per month without insurance, and coverage remains inconsistent. Retatrutide’s arrival is more likely to restart that conversation than resolve it immediately.