The clinical trial was funded by Eli Lilly and the results have not yet been published in a peer-reviewed journal.
“The numbers are definitely impressive,” says Richard Siegel, MD, an endocrinologist at Tufts Medicine Weight and Wellness clinic in Stoneham, Massachusetts who was not involved with the new research. “People have already been asking for it.”
Retatrutide Delivered Powerful Weight Loss Results
The clinical trial, named TRIUMPH‑1, is a phase 3 80-week randomized double-blind placebo-controlled trial. In this type of trial, participants are randomly assigned to receive the drug or a placebo, and neither they nor researchers know which treatment they’ll receive.
For the study, more than 2,300 adults with obesity received retatrutide in doses of 4, 9, or 12 milligrams (mg) or a placebo. Everyone started with a 2 mg dose and increased the amount every four weeks until reaching the targeted dose.
By the end of the trial period, average results showed:
- Those on a 4 mg dose lost 47.2 pounds (lb), or about 19 percent of their starting body weight.
- Those on a 9 mg dose lost 64.4 lb, about 26 percent of their starting weight.
- Those on a 12 mg dose lost 70.3 lb, about 28 percent of their starting weight.
TRIUMPH-1 also included a 24-week extension period for about 500 adults with a BMI (body mass index) of 35 or greater, which is classified as severe obesity. This group continued taking retatrutide up to 9 or 12 mg. People on the maximum dose lost an average of 85 lb after the full 104 weeks, or about 30 percent of their starting weight.
More than 65 percent of participants who took the 12 mg dose reached a BMI below 30 after 80 weeks, which means they were no longer classified as having obesity.
“It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants,” said the lead investigator, Ania Jastreboff, MD, PhD, the director of the Yale Obesity Research Center, in a statement.
Some People on a Placebo Dropped Out Due to Side Effects
Participants taking retatrutide reported side effects similar to those seen with existing weight loss medications. Those included:
- Nausea (about 29 to 42 percent of participants, depending on the dose)
- Diarrhea (25 to 34 percent)
- Constipation (24 to 26 percent)
- Vomiting (11 to 25 percent)
- Upper respiratory tract infection (12 to 14 percent)
Interestingly, more people taking a placebo dropped out of the trial because of side effects than participants taking the lowest dose of retatrutide (4.9 percent compared with 4.1 percent).
Some participants developed urinary tract infections while taking the medication, which Dr. Siegel notes is not considered a side effect for semaglutide or tirzepatide.
What Makes Retatrutide Different
Retatrutide is a triple-agonist medication, meaning it acts on three different hormone receptors in the body: glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon (GCG).
By comparison, semaglutide works on one receptor (GLP-1) while tirzepatide works on two receptors (GLP-1 and GIP).
Dubbed a “triple G” medication, retatrutide is given once a week as an injection, just like its GLP-1 competitors. The medication supports weight loss by reducing appetite and slowing digestion, similar to existing medications in this space.
Retatrutide has already generated a lot of hype from previous clinical trial results. In one earlier study, some participants actually dropped out of the clinical trial because they felt they had lost too much weight too quickly.
“Weight gain and weight loss is a complex interaction of multiple hormones,” says Mir Ali, MD, the medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California. “Any medication that can affect multiple hormones is going to be more effective.”
If Approved, Retatrutide May Be the Most Powerful Weight Loss Drug on the Market
In clinical trials, adults who took tirzepatide lost an average of 15 to 22.5 percent of their starting body weight over 72 weeks. People taking semaglutide injections lost 10 to 15 percent of their starting body weight over 68 weeks.
While researchers haven’t yet directed tested retatrutide against semaglutide or tirzepatide in clinical trials, the latter two medications have been compared in a head-to-head trial.
In that 72-week study, adults taking tirzepatide lost 50 lb on average (about 20 percent body weight). Those who received semaglutide lost 33 lb on average (about 14 percent body weight). That study was funded by Eli Lilly, which makes tirzepatide.
Dr. Ali points out that the retatrutide clinical trials are lasting longer than previous trials for already approved GLP-1 drugs. “A head-to-head comparison is going to be necessary to see the actual long-term comparison of weight loss,” he says.
It’s also possible that the real-world impact of retatrutide will be different, Siegel says. “People in a clinical trial generally do better [with weight loss] than anyone else,” he says.
This Medication Isn’t for Everyone Looking to Lose Weight, According to Doctors
Given its powerful impact, retatrutide may not be the right drug for all adults with obesity, both doctors said.
“This medication is designed for people with significant weight to lose — not just for people with 5 to 10 lb to lose,” Ali says. The same is true for other GLP-1 drugs, he notes.
Retatrutide may be best for people with severe obesity or close to it who have other health conditions, he says.
Siegel agrees. “You don’t want to overdo it. A lot of people want the most effective agent, but not everyone necessarily needs a 25 to 30 percent weight loss,” he says.
When Is the FDA Expected to Approve Retatrutide?
Eli Lilly has not yet submitted data to the FDA for retatrutide approval. For now, it is only legally available for use through clinical trials.
That hasn’t stopped some people from seeking out the medication online.
“Several phase 3 trials evaluating retatrutide are expected to complete in 2026, and Lilly plans to submit retatrutide by the end of 2026 based on the TRIUMPH trials in obesity,” a Lilly spokesperson told Everyday Health.
The company is also testing retatrutide in adults with obesity or overweight and type 2 diabetes, as well as adults with obesity or overweight and heart disease.
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