Lilly’s EloraTZP achieves up to 23.3% weight loss in Phase 2 trial, with discontinuation rates posing a challenge for Phase 3 development

For people facing both obesity and type 2 diabetes, weight loss and improved blood glucose are linked treatment goals, and the ability to use a medication over the long term is equally important. Lilly’s EloraTZP Phase 2b trial, presented at the 2026 European Association for the Study of Diabetes (EASD) Annual Meeting, showed greater potential for weight loss while placing tolerability at the center of the next stage of development.

EloraTZP is an investigational combination of eloralintide and tirzepatide: the former acts on amylin receptors, while the latter acts on GIP and GLP-1 receptors. This strategy aims to further improve metabolic control through three hormonal pathways involved in regulating appetite and blood glucose. HCPLive noted that the trial used separate once-weekly injections of each drug, rather than combining them in a single injection.

The 48-week trial enrolled 367 adults with overweight or obesity and type 2 diabetes, with a mean baseline weight of 105.4 kilograms and a glycated hemoglobin (A1C) level of 8.1%. The study’s primary endpoint was weight change with the combination therapy compared with placebo, while comparisons with other treatments were secondary endpoints. According to the published results, all combination doses met the primary and secondary endpoints.

Mean weight loss across the four combination doses ranged from 13.2% to 23.3%. The highest dose, eloralintide 9 milligrams plus tirzepatide 15 milligrams, produced 23.3% weight loss at 48 weeks, exceeding the 14.8% achieved with tirzepatide 15 milligrams alone by 8.5 percentage points. A1C decreased by 2.2 to 2.9 percentage points with the combination therapy, compared with 2.4 percentage points with tirzepatide alone. The advantage of the highest dose therefore cannot be directly generalized to every combination dose.

Interpreting these figures also requires attention to the analytical approach. BioSpace noted that the reported weight-loss results used an “efficacy estimand,” which estimates the effect when participants continue treatment according to the assigned regimen, without including treatment discontinuation or other deviations from the regimen in the same assessment. The 23.3% figure therefore cannot be viewed as the average outcome that everyone who starts treatment can achieve in everyday use.

Discontinuation data provide important context for this distinction. Across the combination dose groups, 10.8% to 27% of participants discontinued treatment because of adverse events, compared with 2.9% in the tirzepatide-alone group. HCPLive reported that the most common adverse events were gastrointestinal, mostly mild or moderate, and occurred primarily during dose escalation. Even when symptoms are mostly less than severe, they may still affect patients’ willingness and ability to continue treatment.

Lilly plans to begin Phase 3 trials in the fourth quarter of 2026 and adjust the dose-escalation schedule. The company believes that the design used in this trial, which increased the doses of both drugs simultaneously, limited the assessment of eventual tolerability. Whether the new schedule can reduce discontinuation rates, however, remains to be demonstrated in trials. EloraTZP has not yet been approved for marketing. The next stage must determine whether the greater weight loss can be maintained over a longer course of treatment that patients can continue to tolerate.