This article is educational and summarizes published research and news reports. It is not medical advice. Retatrutide, EloraTZP, CagriSema, and trevogrumab are investigational and not FDA-approved. Talk to your prescriber before making any medication decisions.
The 30-second answer
Lilly tested whether adding a second appetite hormone to tirzepatide could push weight loss further in people with type 2 diabetes. It did. The best-performing combination produced about 8.5 percentage points more weight loss than full-dose tirzepatide alone, and better blood sugar control.
The trade-off was that more people quit because of stomach-related side effects. Lilly says that happened because participants were ramping up two medications at once, and it plans to fix the dosing schedule in larger trials (Reuters). Whether that works will decide whether EloraTZP becomes a real option.
What is EloraTZP?
EloraTZP pairs two medications that each act on different hunger and blood-sugar hormones (Lilly):
- Tirzepatide activates the GIP and GLP-1 receptors. It is already approved as Zepbound for weight management and Mounjaro for type 2 diabetes.
- Eloralintide (previously called LY3841136) is an investigational once-weekly selective amylin receptor agonist. Amylin is released after meals and helps create a feeling of fullness. Lilly says eloralintide has minimal activity at the calcitonin receptor, which separates it from some other amylin medications.
Together, the combination activates three hormone pathways the body naturally uses after eating: GIP, GLP-1, and amylin. Lilly's Kenneth Custer called it "an additive and more physiological approach to managing metabolic health."
In this trial, the two medications were given as separate injections. Phase 3 will use a single combined injection.
How the trial worked
| Detail | EloraTZP Phase 2b |
|---|---|
| Trial ID | NCT06603571 |
| Participants | 367 adults with obesity or overweight and type 2 diabetes |
| Locations | United States and Argentina |
| Duration | 48 weeks, double-blind, placebo-controlled |
| Average starting point | 232.4 lb, A1C 8.1% |
| Groups | Placebo, eloralintide alone, tirzepatide 15 mg alone, and four EloraTZP dose combinations |
| Dose escalation | Every four weeks until reaching target dose |
Source: Lilly press release.
The weight loss results
| Treatment arm | Average weight change | Pounds |
|---|---|---|
| Eloralintide 3 mg + tirzepatide 5 mg | −13.2% | −30.7 lb |
| Eloralintide 6 mg + tirzepatide 5 mg | −19.4% | −45.1 lb |
| Eloralintide 6 mg + tirzepatide 10 mg | −19.9% | −46.2 lb |
| Eloralintide 9 mg + tirzepatide 15 mg | −23.3% | −54.1 lb |
| Tirzepatide 15 mg alone | −14.8% | −34.4 lb |
| Eloralintide 3 mg alone | −8.2% | −19.1 lb |
| Eloralintide 6 mg alone | −12.3% | −28.6 lb |
| Eloralintide 9 mg alone | −11.1% | −25.8 lb |
| Placebo | −3.0% | −7.0 lb |
Efficacy estimand at 48 weeks, from Lilly. This estimates results if everyone had stayed on treatment.
Three things the table tells us
- Lower tirzepatide doses still worked well in combination. Eloralintide 6 mg plus tirzepatide 5 mg (19.4%) beat tirzepatide 15 mg alone (14.8%). For people who cannot tolerate high tirzepatide doses, that is an interesting signal.
- Eloralintide on its own is a meaningful medication. Up to 12.3% weight loss in people with type 2 diabetes is comparable to some approved GLP-1 results in this population. Eloralintide alone is already in Phase 3 for obesity.
- Type 2 diabetes makes these numbers more impressive. People with diabetes typically lose less weight on these medications. Citi analyst Geoff Meacham noted that getting this kind of result in type 2 diabetes was significant for exactly that reason (Reuters).
Blood sugar results
| Treatment | Average A1C reduction |
|---|---|
| EloraTZP (best result) | Up to 2.9 points |
| Tirzepatide 15 mg alone | 2.4 points |
| Eloralintide alone (best result) | Up to 1.4 points |
From an average starting A1C of 8.1%, a 2.9-point drop would bring the average participant to about 5.2%, in the normal range. Lead author Liana K. Billings, MD, of Endeavor Health said participants had "substantial weight loss alongside meaningful reductions in A1C. These are outcomes that matter to patients" (Lilly).
Side effects and the dropout problem
This is where investors and clinicians focused their questions.
| Group | Stopped due to side effects |
|---|---|
| EloraTZP (depending on dose) | 10.8% to 27.0% |
| Eloralintide alone | 0% to 10.8% |
| Tirzepatide 15 mg alone | 2.9% |
| Placebo | 16.7% |
Source: Lilly.
The most common side effects were gastrointestinal: nausea, vomiting, diarrhea, and constipation. They were generally mild or moderate and occurred mainly during dose escalation. They were more frequent in the combination groups than with either medication alone.
Two points help put the numbers in context:
- The placebo dropout rate was unusually high at 16.7%. Small Phase 2 trial groups (each arm had roughly 35 to 40 people) can produce noisy numbers.
- Lilly attributes the higher dropout to ramping up two medications at once. It says it will use an optimized, slower escalation schedule in Phase 3 (Reuters).
Not everyone is convinced yet. Kevin Gade of Bahl & Gaynor told Reuters that "the outsized weight loss benefit is being questioned relative to the discontinuation rates and the reality that this is a dual-drug regime." Morningstar analyst Karen Andersen said: "If Lilly can get a handle on the discontinuations and GI tolerability issues, then I think this is looking stronger than retatrutide as a high-efficacy option for patients."
If you are dealing with GI side effects on your current medication, our guide to managing GLP-1 side effects has practical strategies.
EloraTZP vs. retatrutide
Lilly now has two high-efficacy candidates aimed at people who need more than 20% weight loss. Here is how they compare in people with type 2 diabetes, keeping in mind these are different trials with different durations.
| EloraTZP | Retatrutide | |
|---|---|---|
| Targets | GLP-1 + GIP + amylin (two medications) | GLP-1 + GIP + glucagon (one molecule) |
| Best weight result in type 2 diabetes | −23.3% at 48 weeks (Phase 2b) | −20.8% at 80 weeks (Phase 3) |
| Best A1C reduction | Up to 2.9 points | Up to 1.6 points |
| Stopped due to side effects | 10.8% to 27% | 3.8% to 11.6% |
| Stage | Phase 3 starting Q4 2026 | FDA filing planned Q1 2027 |
EloraTZP data from Lilly; retatrutide data from Lilly's TRIUMPH-2 release. Note that the EloraTZP group started with a higher A1C (8.1% vs. 7.7%), which leaves more room to fall.
Custer told Reuters it was possible EloraTZP could produce even greater weight loss than retatrutide in later trials. Lilly executives also said it was too early to define the ideal patient, but that the combination could serve people needing 20% to 30% weight loss or those who do not reach their goals on Zepbound. For the full retatrutide picture, see our TRIUMPH-2 breakdown.
Why combination therapy is the next frontier
EloraTZP reflects a strategy the whole field is moving toward: rather than pushing one hormone signal harder, combine several signals at moderate doses. The idea is that each hormone works through its own receptor, so the effects can add up while each component stays at a tolerable level (Lilly).
The Phase 2b data support that idea in one important way. Eloralintide 6 mg plus tirzepatide 5 mg, a fairly low tirzepatide dose, produced 19.4% weight loss. That is more than full-dose tirzepatide alone (14.8%). For people who struggle with nausea at higher tirzepatide doses, a lower-dose combination could someday be an attractive path.
The data also show the limits. Simply adding a second medication increased gastrointestinal side effects, at least with the escalation schedule used here. The real test for every combination medication, including Novo's CagriSema, is whether the efficacy gains outweigh the tolerability cost once dosing is optimized.
Lilly's lead author Liana Billings framed the goal this way: "We need to continue building on these findings so that, in the future, we can offer patients more treatment options that address both weight and glucose and better reflect the complexity of living with type 2 diabetes and obesity."
What to watch in Phase 3
When Phase 3 results eventually arrive, these are the details that will matter most:
- Dropout rates with the new escalation schedule. If discontinuation falls closer to tirzepatide's 2.9%, EloraTZP becomes much more compelling.
- Results in people without diabetes. This trial included only people with type 2 diabetes. Weight loss is usually larger in people without diabetes.
- Body composition. How much of the weight lost is fat versus muscle. See our coverage of muscle preservation research.
- Longer duration. Forty-eight weeks is a relatively short trial for obesity medications. Many people continue losing weight well past one year.
- Single-injection convenience. The co-formulated product should be easier to use than two separate injections.
When could EloraTZP be available?
- Phase 3 begins in the fourth quarter of 2026, using a co-formulated single injection (Lilly).
- Phase 3 obesity trials typically take one and a half to two years, plus time for FDA review. A realistic approval window is late this decade at the earliest.
- Eloralintide alone is further along, already in Phase 3 for obesity in people with and without type 2 diabetes.
What this means for you
- Zepbound and Mounjaro remain the proven, available option. Tirzepatide alone produced 14.8% weight loss with very few dropouts in this trial.
- The future is likely combination therapy. Novo's CagriSema, Lilly's EloraTZP, and other candidates all pair GLP-1 with amylin. See our CagriSema vs. tirzepatide breakdown.
- Do not try to build your own combination. Eloralintide is investigational. Products sold online as amylin peptides are not the trial medication.
Frequently asked questions
What is EloraTZP?
EloraTZP is an investigational Lilly combination of eloralintide, a selective amylin receptor agonist, and tirzepatide, the active ingredient in Zepbound and Mounjaro. It targets GIP, GLP-1, and amylin pathways.
How much weight did people lose on EloraTZP?
At the highest dose (eloralintide 9 mg plus tirzepatide 15 mg), adults with type 2 diabetes lost an average of 23.3% (54.1 lb) over 48 weeks, compared with 14.8% (34.4 lb) on tirzepatide 15 mg alone.
What are the side effects of EloraTZP?
Mostly gastrointestinal, generally mild to moderate and concentrated during dose escalation. Between 10.8% and 27% of EloraTZP participants stopped due to side effects, compared with 2.9% on tirzepatide alone.
When will EloraTZP be available?
Lilly is starting Phase 3 trials in the fourth quarter of 2026 with a single co-formulated injection. Approval is likely several years away.
Is EloraTZP better than retatrutide?
It is too early to say. The trials differ in length and design. EloraTZP showed a larger A1C drop but higher dropout rates. Lilly and some analysts believe it could rival retatrutide if tolerability improves.
The bottom line
EloraTZP shows that adding amylin to tirzepatide can push weight loss well beyond what tirzepatide does alone, even in type 2 diabetes. Whether it becomes a real option depends on whether Lilly can make it easier to tolerate in Phase 3. For now, tirzepatide alone remains a proven, available choice.
Sources
- Eli Lilly: EloraTZP Phase 2b results (September 30, 2026)
- Reuters: Experimental Lilly combination drug tops Zepbound in weight-loss trial
Educational content written by Rolando Valenzuela, founder of GLPTree. Not medical advice. Talk to your prescriber before starting, stopping, or switching any medication.