What are GLP-3? Meet the new generation of weight loss drugs with three key ingredients
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GLP-1 has become a buzzword in the weight loss community, but now some are touting “GLP-3s,” claiming they are taking obesity medications to the next level.
GLP-1 (glucagon-like peptide 1) medications work by mimicking a natural hormone in the body that helps regulate blood sugar and appetite.
The informal term “GLP-3” refers to a new triple agonist drug that targets three hormones: GLP-1, GIP (glucose-dependent insulinotropic polypeptide, another natural hormone released by the intestine after eating), and glucagon receptors. The most advanced example is Eli Lilly’s retatrutide, based on clinical trial results.
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The New England Journal of Medicine published results from a Phase 2 trial of retatrutide for obesity conducted in 2023, revealing “substantial reductions in body weight” after 48 weeks of treatment.
A 12 mg injection once a week produced a 24.2% weight reduction and participants continued to lose weight after the 48-week trial period.
According to sources, “GLP-3” doses will most likely be once a week. (iStock)
Side effects are reportedly similar to those of GLP-1 medications and typically include gastrointestinal complications such as nausea, vomiting, and diarrhea. Dose-dependent increases in heart rate were observed.
How is it different?
Retatrutide mimics three natural hormones found in the body, compared to GLP-1 which mimics only one hormone, according to a report from GoodRx pharmacists.
The hormones GIP and GLP-1 tell the pancreas to release insulin after eating, while slowing digestion to help initiate feelings of satiety.
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These hormones target the area of the brain that regulates appetite and influences food cravings, the report noted.
The third hormone, glucagon, speeds up metabolism and helps the body break down fat cells for energy. That hormone also tells the liver to produce new sugar, which is kept under control by the activity of GIP and GLP-1, preventing blood sugar spikes.
Participants in the phase 3 trial experienced an average weight loss of 71.8 pounds. (iStock)
“This additional increase in metabolism can complement and complement the actions of GIP and GLP-1. And that is why it appears to provide significant weight loss,” states the GoodRx website. “If approved, retatrutide will be the first in a new class of drugs.”
Eli Lilly announced results from its Phase 3 TRIUMPH-4 trial in December, testing the effect of retatrutide on weight loss and other health conditions.
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Participants with obesity and knee arthritis who took a 12 mg dose of retatrutide experienced an average weight loss of 71.8 pounds (28.7%) at 68 weeks.
The drug also reduced Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores by an average of 75.8%, marking “significant improvements” in comfort level and physical function, according to a news release.
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More than one in eight patients reported being “completely free” of knee pain at the end of the trial.
Seven additional Phase 3 trials for retatrutide are expected to conclude in 2026. The drug could gain FDA approval in 2027, according to GoodRx.
Retatrutide patients with knee osteoarthritis reported improvement in pain after 68 weeks of taking the drug. (iStock)
“We are encouraged by the results from TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function,” Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health, wrote in a statement.
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“With seven additional phase 3 readouts planned for 2026, we believe retatrutide could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis.”
Despite the limited availability of data on the drug, the drug could also be applied to treat other conditions such as type 2 diabetes, kidney disease, cardiovascular risk reduction and metabolic dysfunction, according to GoodRx and other experts.
News senior medical analyst Dr. Marc Siegel noted that Lilly’s Zepbound and Mounjaro already target two metabolic pathways (GLP-1 and GIP) that work together to promote weight loss, reduce hunger and inflammation, improve insulin function and slow digestion.
The doctor confirmed that the new drug, with its third receptor agonist, will further reduce hunger and increase the feeling of satiety.
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“The weight loss in clinical trials is even more substantial, and the most likely reason for decreased orthopedic problems is weight loss: less stress on the joints and less inflammation,” Siegel added.
The most common side effect of GLP-3 is gastrointestinal symptoms, the doctor confirmed. Rare side effects may include pancreatitis, gallstones, and cardiac arrhythmia.
Angelica Stabile is a lifestyle reporter for News Digital.