EloraTZP phase 3 trials registered as Lilly pairs an amylin analog with tirzepatide

Eli Lilly has registered its EloraTZP phase 3 programme, two trials that will test eloralintide, an amylin analog, given together with tirzepatide. The records, first posted on ClinicalTrials.gov on 19 October, plan 3,115 participants in total, with primary completion estimated for October 2029. The step follows a phase 2 trial in people with type 2 diabetes in which the highest dose combination produced 23.3 percent weight loss at 48 weeks, but in which treatment discontinuation for adverse events reached 27.0 percent in one combination arm.

Two EloraTZP phase 3 trials and how they differ

The larger study is AMPLIFY-1 (NCT07881432), which plans to enrol 2,115 adults with obesity who do not have type 2 diabetes. Its design has eight arms: five EloraTZP dose levels, tirzepatide alone, eloralintide alone and placebo, all given as injections under the skin. Participants and investigators are both masked. The AMPLIFY-1 registry record names the percent change in body weight from baseline to week 100 as the primary endpoint, with waist size, triglycerides, systolic blood pressure and high sensitivity C reactive protein among the secondary measures. The listed start is December 2026 and the status is not yet recruiting, so no participant has been dosed yet according to the record.

AMPLIFY-2 (NCT07881458) is smaller and simpler. It plans 1,000 adults with obesity or overweight who also have type 2 diabetes, randomised to EloraTZP or to tirzepatide alone, with no placebo arm. The primary endpoint is again the percent change in body weight at week 100, and HbA1c is a secondary measure. The listed start is November 2026. Biz Chosun, which reported the registrations, noted that both studies are stratified by diabetes status across the programme. The direct comparison with tirzepatide in AMPLIFY-2 is the test that decides whether the amylin add on earns a place, because Lilly already sells tirzepatide on its own and the combination has to beat it.

Phase 2 weight loss and the tolerability cost

The phase 2 trial behind the move (NCT06603571) followed 367 adults with obesity or overweight and type 2 diabetes in the United States and Argentina for 48 weeks. It was double blind and placebo controlled, with arms for placebo, eloralintide alone, tirzepatide alone and four combinations given as separate injections. Mean baseline weight was 105.4 kilograms and mean HbA1c was 8.1 percent. Under the efficacy estimand, the highest dose combination produced 23.3 percent weight loss, against 14.8 percent for tirzepatide alone at its top dose and 3.0 percent for placebo. HbA1c fell by 2.9 percentage points with that combination and by 2.4 points with tirzepatide alone, according to data shown at the EASD meeting in Milan.

Discontinuation because of adverse events ranged from 10.8 to 27.0 percent across the combination arms, against 2.9 percent on tirzepatide alone.

The cost showed up in the safety data. Discontinuation because of adverse events ranged from 10.8 to 27.0 percent across the combination arms, against 2.9 percent on tirzepatide alone. Placebo had a rate of 16.7 percent, a figure that is hard to interpret in a trial this small. Most events were gastrointestinal, generally mild or moderate, and clustered during dose escalation, as reported by Pharmacy Times. Combination arms had more of them than either drug alone. One detail points to a fix: when tirzepatide was raised to its top dose first and eloralintide was added afterwards, gastrointestinal event rates were similar to those seen with tirzepatide alone. The reverse order was not studied.

Why tolerability decides the amylin combination

The phase 2 weight figures describe what happens if everyone stays on treatment, which is exactly the assumption that high dropout rates put in doubt. The trial was built to compare EloraTZP with placebo; the comparisons with tirzepatide alone were not the primary endpoint. With 367 people spread across many arms, each group held only a few dozen participants, so the gap between combination and tirzepatide alone carries wide uncertainty. Biz Chosun reported that Lilly said adverse events came mainly during escalation and that it plans to refine the titration schedule in phase 3. The five EloraTZP arms in AMPLIFY-1 leave room for that kind of tuning, though the records do not describe the schedules in detail.

Lilly is not alone in betting on amylin. Novo Nordisk filed CagriSema, which pairs the amylin analog cagrilintide with semaglutide, with the FDA in December 2025, and the company expects a decision in the fourth quarter of 2026. That puts a rival combination years ahead of EloraTZP on the regulatory path. Other programmes, including single agent amylin analogs such as petrelintide, are moving through phase 2 and phase 3, and readers can compare them on our page of other amylin molecules. The common question for all of them is the same one EloraTZP faces: whether extra weight loss can be delivered without pushing more people off treatment in the first months.

What to watch before AMPLIFY reads out

On our board, the registration moves EloraTZP from phase 2 to phase 3. We treat a public registry entry with a start date and enrolment target as the stage move, while noting that neither trial is recruiting yet. The signal is up, with a caveat. The size of the weight loss in phase 2 is the strongest reason for the move, but the dropout pattern is the strongest reason for caution, and the EloraTZP phase 3 design, with tirzepatide alone as a comparator in both studies, shows that Lilly expects to be judged on the margin over its own drug rather than on the margin over placebo.

The first checkpoints are practical. Both records should switch to recruiting by the end of 2026 if the listed start dates hold. A full peer reviewed paper on the phase 2 trial would let outside readers check the dropout data by arm. After that, the programme goes quiet for a long time: 100 weeks of treatment means primary completion is estimated for October 2029 and study completion for November 2029. In the meantime, the FDA decision on CagriSema will show how regulators weigh an amylin combination. We log each confirmed change in the latest stage moves feed, and we will add AMPLIFY dosing news when the companies or the registry confirm it.

Conclusion

The EloraTZP phase 3 programme gives eloralintide plus tirzepatide a 100 week test in 3,115 people, with tirzepatide alone as the yardstick in both trials. Phase 2 showed 23.3 percent weight loss at the highest dose combination, but also discontinuation rates of up to 27.0 percent. Whether a gentler titration fixes that is the question AMPLIFY must answer before any filing, with primary completion estimated for October 2029.