Eli Lilly said Wednesday that an experimental combination therapy led to greater weight loss than high-dose therapy using its top-selling drug tirzepatide alone in a mid-stage trial in patients with obesity and type 2 diabetes.
This combination therapy achieved the primary goal of the study in a group of patients who typically struggle with weight loss. The results are encouraging, and there is hope that this combination therapy may become a successful alternative for patients who do not respond well to existing GLP-1 medications. Eli Lilly announced that it plans to begin Phase III clinical trials of this therapy by the end of the year.
This combination therapy combines Eli Lilly’s experimental drug eloralintide (which targets amylin, a pancreatic hormone linked to appetite and satiety) with a low dose of tirzepatide (the active ingredient in the injectable obesity drug Zepbound and its diabetes equivalent, Mounjaro).
Tirapate targets two gut hormones: GLP-1 and GIP. Eli Lilly believes that by targeting all three pathways, including amylin, it can further reduce appetite and improve weight loss results—and this combination therapy actually achieved this goal in a 48-week Phase II clinical trial.
Patients receiving the highest dose of combination therapy experienced an average weight loss of 23.3%, or approximately 54 pounds. This regimen combined 9 mg of an amylin-like drug with 15 mg of tesapride.
Meanwhile, patients taking only 15 mg of tilatide experienced an average weight loss of 14.8%, or 34.4 pounds. Patients taking only ileolinide experienced an average weight loss of 12.3%, or 28.6 pounds.
In an interview, Ken Kaster, president of Eli Lilly’s Cardiovascular and Metabolic Diseases Division, said, “Patients may not get the results they want from drugs like tilatide. They may also not get the results they want from drugs like elelinide. The combination of these two drugs to achieve more significant weight loss is undoubtedly the main advantage of this new treatment regimen.”
Combination therapy can also reduce a key blood glucose marker, glycated hemoglobin A1C, by an average of 2.9%. High-dose tezapatide can reduce glycated hemoglobin A1C by an average of 2.4%, while amylin-based medications can reduce it by an average of 1.4%.
Eli Lilly may face additional questions from investors and the medical community regarding patient tolerability and compliance with this highly effective combination therapy.
Among patients receiving combination therapy, the rate of discontinuation due to adverse events was higher (10.8% to 27%, depending on dose) compared with 2.9% among patients receiving telapatide alone during the study.
Among patients taking amylin alone, up to 10.8% discontinued treatment due to adverse events, compared with 16.7% among patients taking placebo.
Eli Lilly stated that the incidence of side effects was higher in the combination therapy group compared to tezapatide or amylin alone. The most common side effects with the combination therapy were gastrointestinal disturbances, typically mild to moderate in severity, and primarily occurring as patients increased their dose during the study.
However, Kaster cautioned against overinterpreting the discontinuation rates of combination therapy in phase II clinical trials. He noted that in a 2018 interim study, the highest dose of tirzepatide also showed a similarly high discontinuation rate, approximately 25%.
”This may not be the best indicator of drug tolerability,” Kuster told CNBC. “We test the efficacy of drug molecules in Phase 1 and 2 clinical trials. We also learn about dosing methods from these studies and make adjustments accordingly. We do this every time.”
Eli Lilly plans to adjust the dosing regimen for the combination therapy in Phase III clinical trials. “We expect to ultimately achieve a very favorable balance between efficacy and tolerability,” Kuster added.
Eli Lilly also plans to move to phase 3 clinical trials of a combination of the two drugs, meaning patients would only need one injection of tirzepatide and eloralintide.
The study results were presented at the annual meeting of the European Association for the Study of Diabetes in Milan, Italy. Eli Lilly announced on Wednesday that it plans to move to Phase III clinical trials of the combination drug by the end of 2026.
Before the release of the Phase 2 study data, some analysts claimed that the study directly compared Eli Lilly’s combination therapy with Novo Nordisk’s next-generation obesity drug CagriSema, which combines amylin and GLP-1-targeting drugs.
He said, “This physiological approach combines three nutrient-stimulating hormones—GLP-1, GIP, and amylin—three hormones the body naturally releases after eating to promote satiety. Their combination could lead to the development of a widely used drug. This method is equivalent to gently activating all three hormonal systems, rather than stimulating any one of them individually.”
Prior to Eli Lilly’s data release, Leerink Partners analyst David Reisinger stated that he believed the amylin-targeting drug eloralintide had the potential to be a “blockbuster” and that the drug was currently being studied as a standalone therapy. In an interview with CNBC, he said the drug’s market potential could “significantly exceed Wall Street’s current expectations,” noting that “millions” of patients have not benefited from existing GLP-1-based therapies or cannot tolerate their side effects.
Reisinger added that Eli Lilly’s combination therapy could also serve as an alternative to a next-generation weight-loss drug that targets three other gut hormones. This therapy, called retartrutide, targets GLP-1, GIP, and another hormone called glucagon, and has demonstrated one of the highest weight-loss rates in clinical trials to date.
The results announced Wednesday further confirmed the positive results obtained in the phase I clinical trial of the amylin-teprazole peptide combination therapy.
Studies have shown that in obese adult patients, adding 3 mg of ileolitinide to a 5 mg telatide regimen resulted in a 17% weight loss after 16 weeks. Eli Lilly stated that, in contrast, using the same dose of telatide alone resulted in only a 10% weight loss.
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Post time: Oct-20-2026