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In a 48-week phase IIb trial, adults with type 2 diabetes taking the highest tested dose of eloralintide plus tirzepatide lost an average 23.3% of their body weight, compared with 14.8% on tirzepatide alone. The combination also had more treatment-related tolerability concerns, including discontinuation due to adverse events in 27% of participants, and it has not yet been tested in phase III.
Adults with type 2 diabetes who received the highest tested dose of investigational eloralintide plus tirzepatide lost an average 23.3% of their body weight over 48 weeks in a phase IIb trial, compared with 14.8% among participants taking tirzepatide alone. The results, presented at the European Association for the Study of Diabetes annual meeting in Milan, suggest the combination may improve weight loss, but the study also found substantially more discontinuations due to adverse events.
The trial’s 23.3% result used the study’s efficacy estimand, a method for analyzing outcomes under specified assumptions about participants’ treatment and follow-up. In the highest-dose combination group, one quarter of participants lost at least 30% of body weight, compared with 12% in the tirzepatide-alone group. The report also cited 20.9% weight loss with tirzepatide in a previous non-diabetes population; that figure comes from a different study and is not a direct comparison within this trial.
Blood sugar measures improved in both groups. HbA1c below 7% was reached by 96% of participants in the highest-dose combination group and the same proportion receiving tirzepatide alone. An HbA1c below 5.7% was reported for 77% and 66%, respectively. These are trial outcomes, not evidence that the combination is approved or appropriate for individual patients.
Tolerability was a notable trade-off. Treatment-emergent adverse events were reported by 84% of the highest-dose combination group, versus 71.4% with tirzepatide alone. Discontinuation because of adverse events occurred in 27% compared with 2.9%. One participant died in a lowest-dose combination group; investigators judged the death unrelated to the study drug, according to the report.
Greater Weight Loss, More Dropouts
The findings matter because weight reduction can be harder to achieve for people with type 2 diabetes using GLP-1-based medicines than for people without diabetes, as the report notes. A combination that produces additional weight loss while maintaining glucose improvements could offer another research path for treating both conditions together. However, the reported efficacy comes from a mid-stage trial, and the higher rate of stopping treatment raises a practical question: whether the added weight-loss benefit can be sustained if more participants cannot tolerate therapy.
Researchers also described the 30% weight-loss result as comparable to a benchmark associated with metabolic surgery. That comparison is a characterization of the observed percentage, not evidence that the medicine and surgery have equivalent outcomes, risks, or durability. The results do not establish long-term benefit, and the study was not designed to answer every question about safety or how the treatment might perform in broader clinical use.
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How the Combination Works
Eloralintide is a selective amylin receptor agonist; tirzepatide acts on both GIP and GLP-1 receptors. The combination is intended to engage three hormone pathways involved in appetite and blood sugar regulation. Eli Lilly said these hormones are released naturally after eating and act through distinct receptors. The investigational drugs were administered as two separate injections in this trial; presenter Liana Billings said work is underway on a single-injection formulation.
The double-blind, parallel-group study randomized 367 adults with overweight or obesity and type 2 diabetes in the United States and Argentina. Participants were assigned across 10 groups, including placebo, eloralintide alone at three dose levels, tirzepatide alone, four combination-dose groups, and a group that began tirzepatide before adding eloralintide at week 24. Eloralintide is also being tested alone in phase III obesity trials.
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Questions Before Phase III
The available report describes 48-week phase IIb findings; it does not establish whether the weight loss will continue, persist after treatment, or translate into improved long-term health outcomes. The full details needed to assess results across all 10 groups, including additional safety information and the handling of missing data, are not provided in the source material. The number of participants in each group and the precision of the estimates are also not specified there.
It is also not yet clear whether the adverse-event discontinuation rate will be similar in larger or longer trials, or whether a single-injection formulation would affect tolerability. The reported 23.3% figure should be understood as an outcome in the highest tested dose group under the efficacy estimand, not as a guaranteed result for patients. The combination remains investigational.
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Lilly Plans Larger Trials
Eli Lilly plans to move the eloralintide-tirzepatide combination into phase III development by the end of the year, according to the report. Those later-stage studies will be needed to test the findings in larger populations and provide more information about safety, tolerability, and sustained effects. Further results may also clarify how different doses compare and whether the combination offers a worthwhile benefit over tirzepatide alone.
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Key Questions
How much weight did participants lose?
In the phase IIb trial’s efficacy estimand, participants in the highest-dose eloralintide-tirzepatide group lost an average 23.3% of body weight over 48 weeks. The tirzepatide-alone group lost 14.8% over the same period.
Did the combination improve blood sugar more than tirzepatide alone?
The report said 96% in both groups reached an HbA1c below 7%. An HbA1c below 5.7% was reported in 77% of the highest-dose combination group and 66% of the tirzepatide-alone group. These figures do not establish how the treatments compare over the long term.
What safety concern appeared in the trial?
Treatment-emergent adverse events were reported in 84% of the highest-dose combination group and 71.4% of the tirzepatide-alone group. Discontinuation due to adverse events was 27% versus 2.9%, respectively. The report said investigators considered one death in a lowest-dose combination group unrelated to the study drug.
Is the combination available as a treatment?
No. Eloralintide plus tirzepatide is investigational and the results are from a phase IIb trial. Eli Lilly plans to advance the combination into phase III development by the end of the year, according to the report.
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