INDIANAPOLIS, Indiana: Eli Lilly's experimental combination obesity treatment helped patients with diabetes lose substantially more weight than its blockbuster Zepbound in a head-to-head mid-stage trial, the drugmaker said September 30.

Patients receiving the highest tested dose of EloraTZP lost an average of 23.3 percent of their body weight over 48 weeks, compared with 14.8 percent for those receiving the highest dose of Zepbound.

EloraTZP combines tirzepatide, the active ingredient in Zepbound and Lilly's diabetes drug Mounjaro, with the experimental drug eloralintide.

Kenneth Custer, president of Lilly's cardiometabolic health division, said in an interview that he expected the combination would offer "the best balance of efficacy, safety, and tolerability" within Lilly's obesity portfolio and among competitors.

He noted that the treatment produced significant weight loss in patients with diabetes, a group that historically faces greater challenges with weight management.

Custer said it was possible the combination could produce even greater weight loss in later trials than retatrutide, another experimental obesity drug from Lilly. The highest dose of retatrutide produced average weight loss of up to 28.3 percent over 80 weeks in patients without diabetes in a late-stage trial.

EloraTZP also reduced blood sugar levels, lowering A1C by as much as 2.9 percent, compared with 2.4 percent for tirzepatide alone, according to data presented at the European Association for the Study of Diabetes meeting in Milan.

However, discontinuation rates for EloraTZP ranged from 10.8 percent to 27 percent, depending on the severity of side effects across the doses tested. That compared with 0 percent to 10.8 percent for eloralintide alone, 2.9 percent for tirzepatide and 16.7 percent for placebo.

The most common side effects were mild to moderate gastrointestinal problems, primarily during dose escalation, and occurred more frequently with the combination therapies than with either drug alone, Lilly said.

The company said the higher discontinuation rate resulted from patients increasing doses of two drugs simultaneously and that it would improve escalation schedules in longer, late-stage trials.

The results come as Lilly and Denmark's Novo Nordisk compete for a global weight-loss market that some analysts forecast could reach US$100 billion to $150 billion annually by the end of the decade.

Novo is on track to launch its combination obesity drug CagriSema early next year. The drug achieved average weight loss of 23 percent over 84 weeks but fell short of Lilly's high-dose tirzepatide in a head-to-head trial in February.

Lilly executives said it was too early to determine the ideal patient profile for EloraTZP, but that it could serve people who require 20 percent to 30 percent weight loss or those who do not reach their goals with Zepbound.

Eloralintide is a selective amylin receptor agonist and targets a different hormone than GLP-1, which Zepbound targets.

The EloraTZP trial involved 367 obese or overweight adults with type 2 diabetes in the U.S. and Argentina. Eloralintide alone resulted in an average weight loss of 12.3 percent at the second-highest dose tested and 11.1 percent at the highest dose, compared with 3 percent for placebo.

Lilly plans to begin late-stage trials of EloraTZP in the fourth quarter of 2026. Late-stage trials of eloralintide in obese and overweight patients with and without diabetes are ongoing.

"Obesity and type 2 diabetes are interconnected, and we are seeing the potential benefit of targeting multiple hormonal pathways to address both," said Liana Billings, the study's lead researcher.