Adding Lilly's new drug to Zepbound helped people lose up to 23% of their weight. But there were more side effects.

By Jaimy Lee

The drugmaker is testing the experimental amylin drug in combination with tirzepatide, which is marketed as Zepbound and Mounjaro

Lilly said EloraTZP, a combination of tirzepatide and an amylin drug called eloralintide, helped people lose between 13.2% and 23.3% of their body weight.

In the race to come up with newer and better weight-loss drugs, Eli Lilly appears to have found a powerful combination.

The pairing of a promising new drug with Zepbound was highly effective in a mid-stage clinical trial but also led to more side effects than expected, Lilly announced Wednesday.

The Indianapolis-based drug giant has been testing eloralintide, its experimental amylin receptor agonist, on its own and in combination with tirzepatide, the megablockbuster GIP/GLP-1 drug known as Zepbound for weight management and Mounjaro for Type 2 diabetes. Like GLP-1s, eloralintide and other amylin receptor agonists help patients lose weight by signaling the feeling of fullness; however, they target different receptors than GLP-1 medications. Lilly refers to the combination as EloraTZP.

A Phase 2 trial tested EloraTZP in 367 adults who were overweight or obese and had diabetes, and it found that the combination helped people lose between 13.2% and 23.3% of their body weight, depending on the dose, after about a year. That's much greater than the 14.8% weight loss reported in participants taking Zepbound alone or the up to 11.1% weight loss for people solely taking eloralintide.

However, the participants taking EloraTZP also experienced more frequent gastrointestinal adverse events, and they discontinued treatment at a far higher rate than people solely taking eloralintide or Zepbound. Between 10.8% and 27% of all patients taking EloraTZP stopped treatment, compared with 10.8% taking eloralintide and 2.9% using Zepbound.

"Although discontinuations were elevated in the higher-dose combination arms, this potentially reflected rapid weight loss," BMO Capital Markets analyst Evan Seigerman told investors. "We view the additive efficacy as important validation of Lilly's next-generation strategy."

Lilly's stock (LLY) was down 1% in Wednesday afternoon trading after the company shared the results. The stock has gained 42% over the past 12 months.

Lilly is banking on eloralintide's success as part of its broader cardiometabolic strategy. The company is already testing the amylin drug in several Phase 3 clinical trials and plans to do so with EloraTZP. If approved, eloralintide is expected to be a huge seller for the company, bringing in $2.6 billion in sales in 2030, according to the FactSet consensus, and could be an option for patients who can't tolerate GLP-1 or GLP-1/GIP drugs.

"Obesity and type 2 diabetes are interconnected," Liana Billings, one of the study's researchers and a clinical researcher at the Endeavor Health hospital system in the Chicago area, said in Lilly's news release. "We are seeing the potential benefit of targeting multiple hormonal pathways to address both."

This is the same thinking that Novo Nordisk (DK:NOVO.B) (NVO) took with CagriSema, its experimental treatment that combines cagrilintide, another amylin receptor agonist, with semaglutide, which is marketed as Ozempic and Wegovy. The Food and Drug Administration is expected to decide whether to approve CagriSema before the end of the year.

Several other drugmakers like AstraZeneca (AZN) and Roche (CH:ROP) are also developing amylin-based drugs for weight loss. The idea is that using or adding amylin to the mix can further lessen the "food noise" that affects many of the people seeking treatment with a GLP-1 drug.

Lilly's growing weight-loss franchise

Lilly's other big weight-loss bet is retatrutide, an experimental drug that targets GLP-1, GIP and glucagon. It's already so popular that people are compounding their own versions of the drug.

The full Phase 3 data for retatrutide, which was also released this week at the same medical meeting, found that people who were obese or overweight with diabetes and who were taking the medication lost between 12.7% and 20.8% of their body weight, depending on the dose. More important, the patients with a body mass index of 35 or higher who took the highest dose of retatrutide were no longer classified as obese after undergoing treatment. That's all alongside the medications that Lilly already sells: Zepbound and Mounjaro, plus Foundayo, a GLP-1 pill.

The EloraTZP study, which came out Wednesday at the European Association for the Study of Diabetes annual conference in Milan, was one of the most anticipated clinical results this week. The data that the company presented this week for its next-generation therapies show that Lilly can continue "to be the key market leader in obesity," according to UBS analyst Michael Yee.

-Jaimy Lee

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09-30-26 1445ET