Lilly Raises Diabetes Weight-Loss Bar with Amylin-Zepbound Combo

 

Lilly Raises Diabetes Weight-Loss Bar with Amylin-Zepbound Combo

**A New Study Just Showed That Adding an Amylin Drug to Tirzepatide Helped Patients with Type 2 Diabetes Lose 23% of Their Body Weight — And Wall Street Is Paying Attention**

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## The Hardest Patients to Treat

Let me tell you about a woman named Denise. She’s 54 years old, lives in a suburb of Dallas, and has been living with type 2 diabetes for eleven years. She’s tried everything. Metformin. Jardiance. Ozempic. She lost some weight on the GLP-1 injection — about 12 pounds — but then her progress stalled. Her A1C was still hovering above 8%. Her doctor kept adjusting her medications, but nothing seemed to move the needle enough.

“It’s frustrating,” she told me. “You do everything right. You eat the salad. You walk every morning. And your body just… fights you.”

Denise is exactly the kind of patient that Eli Lilly had in mind when it designed its newest experimental treatment. And on Tuesday, the company announced results that could change the game for millions of Americans like her.

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## The Study That Stunned Analysts

On September 30, 2026, Eli Lilly presented results from a Phase 2b trial of a combination treatment called **eloraTZP** at the European Association for the Study of Diabetes (EASD) meeting in Milan, Italy .

The treatment combines two drugs:

- **Eloralintide**, an experimental amylin receptor agonist

- **Tirzepatide**, the active ingredient in Zepbound and Mounjaro

The trial enrolled **367 adults** with both obesity (or overweight) and type 2 diabetes — a population that is notoriously difficult to treat because diabetes medications often produce less weight loss than they do in patients without the condition .

### The Headline Number

Patients taking the highest dose of the combination — **9 mg of eloralintide plus 15 mg of tirzepatide** — lost an average of **23.3% of their body weight** over 48 weeks. That’s **54.1 pounds** off an average starting weight of about 232 pounds .

### How It Compares

| Treatment | Average Weight Loss |

|-----------|-------------------|

| **EloraTZP (highest dose)** | **23.3% (54.1 lbs)** |

| Tirzepatide 15 mg alone | 14.8% (34.4 lbs) |

| Eloralintide 6 mg alone | 12.3% (28.6 lbs) |

| Placebo | 3.0% |

The combination didn’t just beat placebo. It beat **tirzepatide alone by more than 8 percentage points** — a difference that analysts called “comfortably above” their expectations .

### The A1C Effect

The combination also lowered **A1C**, the key measure of blood sugar control, by up to **2.9%**. For context, tirzepatide alone lowered A1C by 2.4%, and eloralintide alone by 1.4% .

For patients like Denise, whose A1C remains stubbornly elevated despite treatment, that’s a meaningful difference.

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## Why This Matters: The Amylin Angle

To understand why this combination is such a big deal, you have to understand what amylin is and why drugmakers are so excited about it.

**Amylin** is a hormone that your pancreas releases alongside insulin after you eat. It works in three ways:

- It slows down how quickly food leaves your stomach

- It reduces the amount of sugar your liver produces

- It signals to your brain that you’re full 

The GLP-1 drugs that have dominated the weight-loss market — semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) — work primarily on appetite and digestion. But they don’t target amylin. Adding an amylin drug to the mix is like adding a second lock to a door that was already secured.

“Eloralintide is Lilly’s first amylin-based medicine,” Ken Custer, president of Lilly Cardiometabolic Health, said in an interview with CNBC. “The ability to combine them together and provide even greater weight loss — that’s definitely one obvious benefit” .

Novo Nordisk is pursuing the same strategy with its own amylin-based drug, **cagrilintide**, which it combines with semaglutide in a treatment called **CagriSema** . The competition between these two approaches — Lilly’s amylin + GIP/GLP-1 versus Novo’s amylin + GLP-1 — is shaping up to be the next great battle in the obesity drug wars.

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## The Tolerability Question

Here’s where the story gets more complicated — and where investors and doctors will be asking hard questions.

**More patients on the combination stopped treatment due to side effects.** The discontinuation rate ranged from **10.8% to 27%** depending on the dose, compared to just **2.9%** for tirzepatide alone .

The side effects were primarily **gastrointestinal** — nausea, vomiting, diarrhea — and were generally mild to moderate, mostly occurring during dose escalation .

Lilly’s Custer cautioned against reading too much into the Phase 2 discontinuation rates. He noted that tirzepatide itself had a discontinuation rate of around **25%** in its own mid-stage trial back in 2018. “It’s probably not the best indicator of the tolerability of a medicine,” he told CNBC. “We do things in Phase 1 and Phase 2 to test what the molecule can do from an efficacy perspective. We also learn from those studies about how we should administer them, and then we make changes” .

Analysts at Citi suggested that the high discontinuation rate may have been caused by starting both drugs **simultaneously**, which amplified tolerability challenges. They believe **optimized Phase 3 titration** — ramping up doses more gradually — could preserve the efficacy while improving adherence .

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## Frequently Asked Questions

**Q: What is eloraTZP?**

A: EloraTZP is Eli Lilly’s experimental combination treatment for obesity and type 2 diabetes. It pairs **eloralintide**, an amylin receptor agonist, with **tirzepatide**, the active ingredient in Zepbound and Mounjaro. The combination targets three hormone pathways: GIP, GLP-1, and amylin .

**Q: How much weight did patients lose in the trial?**

A: At the highest dose (9 mg eloralintide + 15 mg tirzepatide), patients lost an average of **23.3% of their body weight** — about **54.1 pounds** — over 48 weeks. This was in patients with both obesity and type 2 diabetes, a population that typically experiences less weight loss than patients without diabetes .

**Q: How does that compare to Zepbound alone?**

A: Tirzepatide 15 mg alone produced **14.8% weight loss** (34.4 pounds) in the same trial. The combination delivered **8.5 percentage points more weight loss** than the standalone drug .

**Q: What about side effects?**

A: Gastrointestinal side effects were more common in the combination arms. Treatment discontinuation rates ranged from **10.8% to 27%** for the combination, compared to 2.9% for tirzepatide alone. Lilly plans to adjust dosing in Phase 3 to improve tolerability .

**Q: When will this treatment be available?**

A: Lilly plans to initiate **Phase 3 trials** in the fourth quarter of 2026. If those trials are successful, the company would then file for FDA approval. This means the earliest possible approval would be in **2029 or 2030** .

**Q: How does this compare to Novo Nordisk’s CagriSema?**

A: Novo’s CagriSema combines **cagrilintide** (an amylin analog) with **semaglutide** (a GLP-1). In the REDEFINE 9 trial, CagriSema produced **21% weight loss** in adults with overweight or obesity at 68 weeks. In the REIMAGINE 5 trial, it produced **12.4% weight loss** in patients with type 2 diabetes, beating tirzepatide 5 mg (9.1%) .

**Q: Why is targeting amylin important?**

A: Amylin works differently than GLP-1 and GIP. It slows digestion, reduces liver sugar production, and signals fullness to the brain. Adding an amylin drug to existing treatments may produce **greater weight loss** by hitting more pathways simultaneously .

**Q: What does this mean for Eli Lilly stock?**

A: Analysts are bullish. BMO Capital maintained a **Buy** rating with a **$1,400** price target. JPMorgan raised its target to **$1,500**. The average analyst price target is around **$1,325**, with 25 of 30 analysts recommending Buy or Strong Buy .

**Q: Is this better than Lilly’s other experimental drug, retatrutide?**

A: They’re different approaches. Retatrutide is a **single molecule** that targets three receptors (GIP, GLP-1, and glucagon). EloraTZP is a **combination of two separate drugs**. In patients with type 2 diabetes, eloraTZP produced 23.3% weight loss, while retatrutide produced about **20.8%** in a similar population. But retatrutide has shown **higher weight loss in patients without diabetes** — up to 25% .

**Q: What is retatrutide?**

A: Retatrutide is Lilly’s investigational “triple G” drug that targets GIP, GLP-1, and **glucagon** receptors. In Phase 3 trials, it produced up to **25% weight loss** in adults with obesity without diabetes, and also reduced knee osteoarthritis pain and sleep apnea severity. Lilly plans to file for FDA approval in **early 2027** .

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## Conclusion: A New Frontier in Obesity Treatment

Here’s what I keep coming back to when I think about Denise, the patient in Dallas who felt like her body was fighting her.

For decades, obesity and type 2 diabetes were treated as separate conditions with separate medications. A patient might take metformin for blood sugar and a GLP-1 for weight, but the two treatments didn’t necessarily work together. The results were often disappointing — especially for patients with both conditions.

Lilly’s eloraTZP data suggests a different path. By combining drugs that target **three different hormone pathways** — GIP, GLP-1, and amylin — the company achieved weight loss in diabetes patients that rivals what the best drugs achieve in patients without diabetes.

That’s not just a scientific achievement. It’s a statement about where obesity medicine is heading. The future isn’t about finding one magic bullet. It’s about **combining treatments** that work through complementary mechanisms, tailoring the approach to the patient’s specific biology.

Denise hasn’t tried eloraTZP. It won’t be available for years. But when it is, she might finally have an option that works for her body.

“I’m not asking for a miracle,” she told me. “I’m asking for something that actually helps.”

Lilly just moved one step closer to delivering that.

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## Disclaimer

**This article is for informational and educational purposes only. It does not constitute medical, investment, or financial advice. The author has no position in Eli Lilly (LLY), Novo Nordisk (NVO), or any related securities. Information presented here is based on publicly available sources and reported figures as of the publication date. EloraTZP is an investigational treatment that has not been approved by the FDA. Clinical trial results do not guarantee future approval or commercial availability. Individual results may vary. Always consult with a qualified healthcare provider before starting, stopping, or changing any medication. Investing involves risk, including the potential loss of principal. Always consult with a qualified financial advisor before making any investment decisions.**