Retatrutide: The Shot That Rivals Weight-Loss Surgery

People with type 2 diabetes lost up to 60 pounds on Eli Lilly's experimental drug retatrutide — about 23 percent of their body weight — according to late-stage trial results published September 29, 2026 in The Lancet. It is the most weight loss ever recorded in a drug trial for diabetes patients, a group that has historically struggled to shed pounds on existing medications, NBC News reported.

The results come from TRIUMPH-2, a Phase 3 trial of more than 1,110 adults with obesity and type 2 diabetes. Participants taking the highest weekly dose lost an average of 49.6 pounds over 80 weeks, and those starting with a body mass index of 35 or higher lost up to 60.8 pounds. More than half of participants no longer met the BMI cutoff for obesity by the end of the trial, and blood sugar improved sharply: A1C fell by up to 1.6 percentage points, with 40 percent of participants reaching the normal range, according to Lilly's announcement of the detailed results.

Retatrutide is a first-in-class triple hormone receptor agonist, targeting GIP, GLP-1 and glucagon receptors in a single weekly injection. The drug is still investigational and has not been approved by regulators.

Retatrutide was tested at three weekly doses — 4 mg, 9 mg and 12 mg — against a placebo over 80 weeks, and all three doses delivered substantial weight loss and blood-sugar reductions, with effects scaling by dose. The triple action is the differentiator: while existing drugs mimic one or two gut hormones, the added glucagon component is thought to raise energy expenditure as well, though researchers are still untangling exactly how much each pathway contributes to the total effect.

How the numbers compare

The figures dwarf what current drugs achieve in diabetes patients. In clinical trials, semaglutide helped people with type 2 diabetes lose up to 10 percent of body weight (about 21 pounds) and tirzepatide up to 15 percent (about 34 pounds) — though NBC noted those are not direct comparisons, since the drugs were never tested head to head against each other.

A second set of results, published the same week in the New England Journal of Medicine, tested the drug in people with obesity who do not have diabetes. Those patients lost up to 70 pounds, or a quarter of their body weight, after 80 weeks. A subset with severe obesity lost up to 85 pounds — 30 percent of body weight — after 104 weeks, the most weight loss ever recorded in a medication trial and roughly on par with bariatric surgery. Dr. Susan Spratt, an endocrinologist at Duke Health who was not involved in the trials, told NBC the drug "rivals gastric bypass surgery without the surgery," calling it "truly an advance in diabetes care."

Why it matters — and what could hold it back

The findings land at a moment of growing alarm about diabetes itself. A Danish study presented at the same EASD meeting in Milan found that obesity-related cancers were 45 percent higher in men and 30 percent higher in women with type 2 diabetes than in those without, based on 27 years of data, KFF Health News reported. The study has not yet been peer reviewed, but it underscores why better diabetes treatments carry stakes far beyond the scale.

Still, Retatrutide is not a finished story. As an investigational drug it has no approved label, no price and no insurance coverage yet — and the GLP-1 class has faced recurring questions about access, long-term side effects and weight regain after patients stop treatment. Trial investigator Dr. Juan P. Frías said results like these "may change what we set out to achieve with a single therapy" for people living with both conditions, but regulators will have the final word.

Doctors not involved in the trial struck a careful note alongside the excitement: diabetes care still rests on the basics of diet, movement and consistent monitoring, and anyone curious about the new class of drugs should talk to their clinician rather than chasing headlines. Retatrutide's next hurdle is regulatory review, where safety data from thousands of trial participants will face months of scrutiny before any approval decision is made.

For the millions managing type 2 diabetes alongside obesity, the message is cautiously hopeful: a single weekly shot that tackles both blood sugar and weight at a scale previously seen only in the operating room is now one step closer to reality. More on the Health beat.