Lilly reports greater weight loss with EloraTZP, but higher withdrawal rates

Lilly says its experimental combination EloraTZP produced greater average weight loss than tirzepatide alone in a 48 week trial of adults with type 2 diabetes and overweight or obesity. The company's September 30 results also showed a higher proportion stopping the combination because of adverse events, a concern Lilly plans to address as it moves toward Phase 3. EloraTZP is investigational, not an FDA approved treatment.[1]

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A comparison within one trial

The study tested whether adding eloralintide, which acts on the amylin receptor, could improve on tirzepatide's effects. Lilly reported average weight loss of up to 23.3% with the combination, compared with 14.8% with tirzepatide alone and 3.0% with placebo at week 48.[1] The largest combination result is an estimate assuming participants remained on treatment, not a description of what happened to every person who entered the trial.[1]

The randomized, double blind Phase 2b study enrolled 367 adults in the United States and Argentina. Participants and investigators were unaware of the assigned treatment; the registry identifies the study as NCT06603571 and records its completion in September.[1][2]

The difference between the largest combination weight change and the tirzepatide result was 8.5 percentage points. Lilly expressed those results as average losses of 54.1 pounds and 34.4 pounds, respectively, from an overall starting weight of 232.4 pounds.[1] These are group averages, not predictions for an individual.

Lilly also reported a fall in blood sugar. In the same comparison, HbA1c, a measure of blood sugar control, declined by 2.9 percentage points with the combination and 2.4 points with tirzepatide, from an overall starting average of 8.1%.[1][4]

The main question specified for the study was whether the combination reduced body weight more than placebo. Comparisons with the active medicines were secondary endpoints.[1][4] Lilly's announcement does not provide the analysis group sizes or confidence intervals alongside these estimates, so the precision of the differences remains difficult to judge from the summary.[1]

Why the withdrawals matter

Lilly's headline results use an efficacy estimand, an analysis estimating what would happen if randomized participants remained on their assigned intervention for 48 weeks, allowing interruptions or modifications.[1] That assumption matters when people stop because of side effects.

Lilly reported higher rates of stopping because of adverse events in the combination groups than in the tirzepatide group. Its release provides a range across the combination groups without identifying each group's rate or analysis denominator, so the highest withdrawal rate cannot be assigned to the group with the largest reported weight change.[1]

The most common adverse events involved the gastrointestinal system and were generally mild or moderate, occurring mainly while treatment was being increased under the study protocol, Lilly said.[1] The discontinuation figures count those who stopped because of adverse events, not everyone who experienced one.

Lilly executive Kenneth Custer told CNBC that the company intends to change how the combination is introduced in Phase 3 and expects a better balance of efficacy and tolerability.[3] That is the developer's expectation, not a result from the planned study.

Adding a different hormone signal

Tirzepatide acts on receptors for GIP and GLP-1, hormones involved in the body's response to food. Eloralintide acts on the amylin receptor, adding another pathway involved in hunger and blood sugar regulation.[1][4] The combination is intended to engage those complementary signals together.[1]

The result applies to the population tested. All participants had type 2 diabetes as well as overweight or obesity, and the registry required a body mass index of at least 27.[2] The study is not a direct comparison with retatrutide or another company's investigational medicine.[2]

Lilly funded the trial. The European Association for the Study of Diabetes, where the findings were presented, disclosed industry consulting and research relationships for lead investigator Liana Billings, including with Lilly.[4]

The next trial has two jobs

Lilly plans to start Phase 3 trials of a co-formulated product containing both compounds by the end of 2026, using a revised escalation schedule.[1] The two components were given separately in Phase 2b.[1] A new formulation and schedule therefore still need to be tested.

A fuller report of the completed study would also help. The registry has no posted results, and the announcement supplies neither a complete adverse-event breakdown nor the outcome regardless of whether participants stayed on treatment.[1][2]

The Phase 2b readout gives Lilly a reason to pursue the combination. The next evidence must show whether the added effect persists under a schedule that more participants can tolerate.[1][3]

Frequently asked questions

Were the ingredients combined into one product in this study?

No. Lilly says the components were administered separately in Phase 2b. The company plans to test a co-formulated product containing both compounds in Phase 3.

[1]

Does the result apply to people without type 2 diabetes?

This trial cannot answer that question: its participants all had type 2 diabetes alongside overweight or obesity. The registry's enrollment criteria define that population.

[2]