Lilly's Retatrutide Cut Body Weight Up to 20.8 Percent in a Diabetes Trial. It Still Isn't Approved.

Two drugs already approved for type 2 diabetes, semaglutide and tirzepatide, produce average weight loss of roughly 10 percent and 15 percent in people with the disease, based on their own trial data. A third drug, not yet approved anywhere, cleared both of those marks this week. Eli Lilly's retatrutide produced an average weight loss of 20.8 percent, about 49.6 pounds, over 80 weeks in adults with type 2 diabetes and obesity or overweight. That is the largest average weight loss recorded in a trial that specifically enrolled people with diabetes, a population whose insulin resistance has historically blunted how much weight these drugs take off.

The results come from TRIUMPH-2, a phase 3, randomized, double-blind, placebo-controlled trial run at 92 sites across eight countries. Researchers screened 2,047 adults and randomly assigned 1,152 of them, all with type 2 diabetes on stable treatment for at least 90 days, to weekly injections of retatrutide at 4, 9, or 12 milligrams, or to placebo. The findings were presented September 29 at the European Association for the Study of Diabetes's 62nd annual meeting in Milan and published the same day in The Lancet.

The numbers move depending on who gets counted

The Lancet paper itself sits behind a paywall, so this account relies on how outlets covering the trial summarized the published data, and their dose-by-dose figures vary by a few points. One summary put the 12-milligram group's average weight loss at 18.8 percent; NBC News reported the same dose at 20.8 percent. That kind of spread usually traces to which patients get averaged in, everyone who was randomized versus only those who stayed on the drug the full 80 weeks, a standard split in how obesity-drug trials report results. Either way, the direction and the rough size of the effect are not in dispute: at the lowest dose, average loss was 11.9 percent; at 9 milligrams, 16.8 percent; at placebo, about 5.1 percent.

Blood sugar control moved alongside the weight loss. The 9-milligram dose cut A1C by roughly 1.5 percentage points, against about 0.2 to 0.45 points for placebo depending on the analysis cited. Up to 40 percent of participants on the higher doses brought their A1C below 5.7 percent, a threshold inside the normal range. On the 12-milligram dose, 72 percent of participants reached an A1C of 6.5 percent or lower, the general clinical target for diabetes control.

“It rivals gastric bypass surgery without the surgery.”

Spratt told NBC News the data "is truly an advance in diabetes care," and pointed to a frustration common among her patients: managing diabetes carefully while still gaining weight. A colleague in the same health system was more measured. Dr. Michelle Ponder, an assistant professor of medicine at Duke University School of Medicine, called the retatrutide data "very exciting" but said the drug "may be too strong for some patients," particularly those with milder diabetes or less excess weight, who she said "may be better suited to the medications we already have available on the market such as Ozempic or Mounjaro." She also flagged a practical point often left out of trial coverage: switching between these drugs carries its own risk of a different side-effect pattern, not just a different number on the scale.

What the trial cost in side effects

• Diarrhea, nausea, constipation, and vomiting occurred more often on retatrutide than on placebo, described as mostly mild to moderate.
• Blood pressure dropped modestly across dose groups, by roughly 1 to 6 percent.
• Dysesthesia, an abnormal skin sensation, showed up in 4 to 7 percent of participants on the drug.
• About 8 percent of participants on the highest dose stopped taking it because of side effects, compared with about 5 percent on placebo.
• Seven deaths occurred during the trial; investigators judged none of them related to the drug.

Nothing here is for sale yet

Retatrutide remains investigational. Eli Lilly has said it plans to file a Biologics License Application with the FDA in the first quarter of 2027, which means a decision, let alone a pharmacy shelf, is still a long way off. The TRIUMPH-2 results are also one piece of a larger program: Lilly has reported separate, additional phase 3 retatrutide trials in people with obesity but without diabetes, where weight loss ran higher still. The diabetes-specific numbers in this trial are the more conservative end of what the company is reporting across its program.