Eli Lilly’s highly anticipated GLP-1 drug retatrutide helped people with Type 2 diabetes lose up to 60 pounds, or about 23% of their body weight, according to late-stage trial results published Tuesday in The Lancet.
It’s the most weight loss ever recorded in a drug trial for diabetes patients, a group that often has a harder time losing weight.
In clinical trials for semaglutide and tirzepatide, people with Type 2 diabetes lost up to 10% (21 pounds) and 15% (34 pounds) of their body weight, respectively. (Those are not direct comparisons, as the drugs were not evaluated in head-to-head clinical trials.)
Retatrutide “is truly an advance in diabetes care,” said Dr. Susan Spratt, an endocrinologist and the senior medical director for the Population Health Management Office at Duke Health in North Carolina. She was not involved in the trial and does not receive money from Eli Lilly. “It rivals gastric bypass surgery without the surgery.”
Spratt said many diabetes medications, such as insulin, cause weight gain.
“It can be discouraging to manage your diabetes well but gain weight,” she said.
Lilly’s trial included more than 1,110 patients who had an average starting weight of about 234 pounds and an average body mass index, or BMI, of about 38. People were randomly assigned to take one of three weekly doses of retatrutide or a placebo for 80 weeks. By the end of the trial, more than half of participants’ BMI fell below 30, the cutoff for obesity.
Results from another trial, published Tuesday in the New England Journal of Medicine, found retatrutide helped patients without Type 2 diabetes who have obesity or are overweight lose up to 70 pounds, or 25% of their body weight on average, after 80 weeks. That data included a subset of patients with severe obesity, who lost up to 85 pounds, or 30% of their body weight, after 104 weeks — the most weight loss ever recorded in a medication trial and on par with bariatric surgery.
Like semaglutide and tirzepatide, retatrutide works by mimicking a hormone called GLP-1. What sets retatrutide apart is its classification as a “triple agonist.” Lilly’s tirzepatide, a “double agonist,” mimics two hormones (GLP-1 and GIP), and retatrutide targets three by adding a hormone called glucagon.
Lilly hasn’t submitted retatrutide for approval to the Food and Drug Administration, but its clinical trial results have already cemented it as one of the drug industry’s most highly anticipated treatments. Lilly says it plans to file for approval early next year.
Unauthorized, copycat versions of retatrutide are already being made and sold through wellness platforms, med spas and compounding pharmacies. The drug is often labeled as “for research use only,” a legal workaround to sell compounds they claim aren’t meant for humans. Lilly has filed lawsuits against companies selling unapproved versions of the drug.
Retatrutide’s other benefits
Retatrutide also helps reduce the severity of sleep apnea and lower knee arthritis pain. Earlier data suggests the drug appears to help the heart.
FOR SUBSCRIBERSA harrowing ordeal aboard an Israel-bound plane
FOR SUBSCRIBERSThe debate over AI’s future rages on both coasts
FOR SUBSCRIBERSObama boosts Senate Democrats with October fundraiser
The new trial found that retatrutide, like other GLP-1 drugs, which were initially developed as diabetes medications, effectively lowered blood sugar levels in patients with diabetes.
FOR SUBSCRIBERSA harrowing ordeal aboard an Israel-bound plane
FOR SUBSCRIBERSThe debate over AI’s future rages on both coasts
FOR SUBSCRIBERSObama boosts Senate Democrats with October fundraiser
Retatrutide lowered A1C levels — a measure of a person’s average blood sugar levels over the previous two to three months — by up to 1.6%, compared with 0.2% with a placebo, according to the trial results.
Up to 40% of patients in the trial reached an A1C below 5.7%, below the cutoff for diabetes and prediabetes.
“The retatrutide data is very exciting,” Dr. Michelle Ponder, an assistant professor of medicine at Duke University School of Medicine in North Carolina, wrote in an email. A 5.7% A1C level means “that their diabetes went into remission,” said Ponder, who was not involved with Lilly’s trial.
She added, however, that retatrutide “may be too strong for some patients,” particularly those with only mild diabetes or slightly elevated weight.
They “may be better suited to the medications we already have available on the market such as Ozempic or Mounjaro,” she said.
She added that whenever switching medications, there is a chance patients could experience a change in the frequency of side effects.
Side effects of retatrutide were similar to those of other GLP-1 medications, with patients most commonly reporting diarrhea, nausea, constipation and vomiting. Lilly said the side effects were mild to moderate in severity. About 8% of people in the trial taking the highest dose stopped taking the drug, compared with about 5% of people taking the placebo.
