Lilly moves a Zepbound add-on that boosted weight loss into big trials

Eli Lilly is moving a two-drug weight-loss shot into the last and largest stage of testing. The treatment pairs tirzepatide, the active drug in Zepbound (sold as Mounjaro for diabetes), with eloralintide, an experimental drug that copies a natural fullness hormone called amylin¹. Lilly calls the combination EloraTZP¹.

According to the U.S. trial registry, Lilly recently registered two global Phase 3 trials of the combination, named AMPLIFY-1 and AMPLIFY-2¹. Phase 3 trials are the large studies a drug usually needs before a company can ask for approval. Together they plan to enroll 3,115 people, the design is stratified by whether patients have type 2 diabetes, and both aim to finish in November 2029, ChosunBiz reported¹.

What happened

The move follows results Lilly presented on September 30, 2026, at the European Association for the Study of Diabetes meeting in Milan². At the time, Lilly said it planned to start final-stage testing by the end of 2026². AllSci reported that Lilly planned to start those trials in the last three months of 2026, using a single combined product and what the company called an optimized way of stepping up the dose³.

That combined product matters. In the earlier study, the two medicines were given as separate weekly shots⁴. For the new trials, Lilly is developing a version that puts both into one injection².

Tirzepatide acts on two gut-hormone pathways, GLP-1 and GIP, which help control blood sugar and curb appetite¹. Amylin is a hormone the pancreas releases along with insulin when you eat⁴. It signals fullness to the brain and slows how fast food leaves the stomach¹. Lilly’s idea is that acting on all three pathways may curb hunger more than either drug alone².

The evidence so far

The main earlier study ran for 48 weeks in 367 adults who had obesity or overweight plus type 2 diabetes¹. It took place in the U.S. and Argentina, and people were split into ten groups: a placebo (dummy shot), eloralintide alone, tirzepatide alone, or one of several combination doses⁴. People started at about 232 pounds on average⁴.

• Top combination dose (9 mg eloralintide plus 15 mg tirzepatide): 23.3% average weight loss, about 54 pounds².
• Tirzepatide 15 mg alone, the top dose of Zepbound: 14.8%, about 34.4 pounds².
• Other combination doses: 13.2% to 19.9%, so the lowest one did a little less than tirzepatide alone⁴.
• Eloralintide alone: 8.2% to 12.3%⁴.
• Placebo: 3.0%⁴.

Blood sugar improved too. A1C, a blood test that reflects average blood sugar over recent months, fell by up to 2.9 points on the combination, versus 2.4 points on tirzepatide 15 mg alone and up to 1.4 points on eloralintide alone². People started with an average A1C of 8.1%⁴. All combination doses met the study’s main goal of more weight loss than placebo³.

An earlier, smaller study pointed the same way. People who took 3 mg of eloralintide on top of 5 mg of tirzepatide lost 17% of body weight on average over 16 weeks, versus 10% with 5 mg of tirzepatide alone²⁵. The Incretin Space, an independent newsletter, described the early data as coming from two small studies with groups of usually 12 to 16 people and dropouts in most groups⁶.

Eloralintide on its own has its own track record. In a separate 48-week study of 263 adults with obesity or overweight but without type 2 diabetes, average weight loss ranged from 9% at the lowest dose to 20% at 9 mg, versus 0.4% on placebo⁷. Those results were published in The Lancet⁷, and the trial’s registry record lists it as completed⁸.

The catch: how many people stopped

For weight-loss drugs, whether people can keep taking them is as important as how much weight they lose, ChosunBiz noted¹. Here the combination looked weaker. Between 10.8% and 27.0% of people on the combination doses stopped treatment because of side effects, depending on the dose¹. On tirzepatide 15 mg alone, 2.9% stopped¹. Up to 10.8% stopped on eloralintide alone, and 16.7% on placebo².

Most side effects were stomach and gut problems such as nausea and vomiting, generally mild to moderate¹. They were more common in the combination groups than with either drug alone and tended to appear while doses were being increased². Lilly said this is why it plans to change the dose-increase schedule in the new trials¹.

Kenneth Custer, who leads Lilly’s cardiometabolic business, told CNBC that dropouts in mid-stage trials are “probably not the best indicator of the tolerability of a medicine,” pointing out that about 25% stopped at tirzepatide’s highest dose in a 2018 mid-stage study². He added:

“We expect that we’ll end up with a very favorable balance of efficacy and tolerability.”

That expectation is what the new trials are meant to test².

What it does not show yet

Several limits apply to the earlier results.

• The comparison with Zepbound was a side question. The study was mainly built to test the combination against placebo. The comparison with tirzepatide alone was a secondary measure¹.
• Small groups. Each dose group had only about 37 people¹.
• Best-case math. The weight-loss figures assume people stayed on treatment, even though many did not¹. Counting everyone who started usually gives a lower number⁴.
• Not yet peer reviewed. The combination results come from a press release and a conference talk, with no journal paper yet⁴.
• One group of patients, one year. The data come from a single study in people with type 2 diabetes, and 48 weeks leaves longer-term effects unknown³.

Who is behind it, and the race around it

Lilly is developing and paying for the combination, and the results so far are company-reported⁴. Lilly is also testing eloralintide alone in several final-stage trials, including in people with type 2 diabetes, in people with sleep apnea, and as an add-on for people whose weight loss has stalled on existing weekly shots⁹.

The combination competes inside Lilly with retatrutide, a drug that acts on three hormone pathways. In a final-stage trial in people with obesity or overweight and type 2 diabetes, retatrutide produced 20.8% average weight loss at 80 weeks³. Comparing across trials is limited by differences in design, dose and length³. Retatrutide is expected to be filed for FDA approval next year¹.

Other companies are betting on amylin too. Novo Nordisk’s CagriSema, which pairs an amylin-like drug with semaglutide (the drug in Ozempic and Wegovy), is under U.S. regulatory review¹. Zealand Pharma and Roche are developing petrelintide, another amylin drug³. In Korea, Celltrion is developing a drug aimed at four pathways, including amylin, and plans to present animal and lab results in November¹.

Analysts are watching the money as well. Leerink Partners analyst David Risinger called eloralintide a “mega-blockbuster” prospect².

What to watch next

• Whether the AMPLIFY trials start enrolling on schedule, and the first details of their design.
• Whether the new dose-increase schedule and single injection lower the share of people who stop because of nausea and vomiting, the central question raised by the earlier study¹.
• A peer-reviewed paper on the 367-person study, with results that count everyone who started.
• Results from the large trials, which aim to finish in November 2029¹.

Neither eloralintide nor the combination is approved anywhere, and both have only been given inside clinical trials⁴.