Patients shed 23.3% of body weight over 48 weeks as side-effect dropouts climbed
A combination of the experimental amylin drug eloralintide and tirzepatide produced average weight loss of 23.3 percent over 48 weeks at its highest tested dose in adults with type 2 diabetes and obesity, against 14.8 percent for the highest dose of tirzepatide alone.
Indianapolis-based Eli Lilly presented the Phase 2 results for the regimen, known as EloraTZP, at the European Association for the Study of Diabetes meeting in Milan, Italy, Reuters reported.
The multi-arm trial assigned 367 obese or overweight adults with type 2 diabetes in the United States and Argentina to eloralintide, tirzepatide, the two drugs together, or a placebo.
Patients on the highest combination dose, 9 mg of eloralintide with 15 mg of tirzepatide, lost an average of about 54 pounds, according to CNBC.
Eloralintide alone produced average weight loss of 12.3 percent at the second highest dose tested, Reuters reported, while patients on placebo lost 3 percent.
CNBC reported Tirzepatide is the active ingredient in Lilly's obesity injection Zepbound and its diabetes drug Mounjaro, and targets the gut hormones GLP-1 and GIP.
Eloralintide belongs to a class known as selective amylin receptor agonists, which target a different hormone.
Lilly said the combination lowered A1C, a measure of average blood sugar, by up to 2.9 percent, against up to 2.4 percent for higher-dose tirzepatide, according to CNBC.
Bloomberg reported an average baseline A1C of 8.1 percent, and that up to three quarters of patients on the high-dose combination reached normal blood sugar levels.
"It is a wow," said Julio Rosenstock, a professor of medicine at the University of Texas Southwestern Medical Center and an investigator in the study, in comments reported by Bloomberg.
Between 10.8 percent and 27 percent of patients on the combination stopped treatment because of side effects, depending on the dose tested, Reuters reported.
That compared with a dropout rate of zero 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 issues that occurred mainly during dose escalation.
Bloomberg reported that more than four-fifths of the highest-dose combination group reported a side effect of some kind, with about half experiencing nausea.
"The outsized weight loss benefit is being questioned relative to the discontinuation rates and the reality that this is a dual-drug regime," said Kevin Gade, chief operating officer at Bahl & Gaynor, which holds Lilly shares, in comments to Reuters.
Kenneth Custer, president of Lilly's cardiometabolic health division, attributed the higher discontinuation rate to patients ramping up doses of two drugs at once, and said escalation schedules would be improved in late-stage trials, Reuters reported.
Lilly plans to begin late-stage trials of EloraTZP in the fourth quarter of 2026, Reuters reported, and is also advancing a co-formulation requiring a single injection, according to CNBC.
The same outlet reported that retatrutide, another Lilly experimental obesity medication, drove an average weight reduction of up to 28.3 percent over 80 weeks at its highest dose in a late-stage trial in patients without diabetes.
Custer said the combination could produce greater weight loss in later trials.
Novo Nordisk's CagriSema, which combines cagrilintide with semaglutide, fell short of Lilly's high-dose tirzepatide in a head-to-head trial in February, despite achieving a 23 percent average weight reduction over 84 weeks, Reuters reported.
