In 2023, the U.S. Food and Drug Administration (FDA) approved Zepbound® (tirzepatide) for chronic weight management. Zepbound® belongs to a class of medications called glucagon-like peptide-1 receptor antagonists, or GLP-1 RAs.

Zepbound®’s manufacturer, Eli Lilly, is working on a new GLP-1 RA formulation called retatrutide. Unlike tirzepatide, retatrutide isn’t approved by the FDA yet. But early weight loss results are promising, so you may be wondering whether it’s better to start Zepbound® now or wait until retatrutide trials conclude.

To help you decide, we’ll compare Zepbound® versus retatrutide and explore what the research shows about both. 

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How do Zepbound® and retatrutide work?

Zepbound®’s active ingredient is called tirzepatide. An “active ingredient” is the part of the drug mainly responsible for its desired effect—in this case, weight loss. Tirzepatide is a dual agonist, which means it mimics two hormones the body naturally produces: 

• Glucagon-like peptide-1 (GLP-1) is an incretin hormone, meaning it prompts the pancreas to release insulin and regulate blood sugar levels. The hormone also slows how quickly food leaves the stomach and suppresses appetite.
• Glucose-dependent insulinotropic polypeptide (GIP) is another incretin hormone, but it’s more closely associated with how the body uses and stores fat. 

Retatrutide is a triple agonist. It targets GLP-1 and GIP, plus a third: glucagon. Glucagon is a hormone that the pancreas produces. Its main job is to regulate blood sugar levels. It does this by telling your liver to release stored glucose when levels run low. Glucagon also plays a role in how the body breaks down and burns stored fat. 

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How Zepbound® and retatrutide compare

While these medications both encourage weight loss, they have a few key differences:

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Zepbound® (tirzepatide) vs. retatrutide weight loss comparison: What does clinical research show?

Let’s explore and compare what the evidence says about Zepbound® (tirzepatide) and retatrutide.

SURMOUNT-1

SURMOUNT-1, a phase 3 trial published in the New England Journal of Medicine in 2022, looked at tirzepatide’s safety and efficacy for weight loss. It enrolled 2,539 adults who had obesity or were overweight with a weight-related condition. None had diabetes. 

Over 72 weeks, participants took one of three tirzepatide doses: 5 mg, 10 mg, or 15 mg—or a placebo. Those on the 15 mg dose lost an average of approximately 21% of their body weight. This is a meaningful jump from the placebo group, who lost 3% on average. 

Outcomes on other doses were meaningful, too. The 5 mg group lost an average of 15%, while the 10 mg group lost an average of 19.5%. Approximately nine in 10 participants taking tirzepatide lost 5% or more of their body weight. 

Beyond numbers on the scale, researchers also looked at:

• Cardiometabolic health: Tirzepatide improved several markers linked to metabolic and heart health compared with placebo, including waist circumference, blood pressure, and fasting insulin.
• Prediabetes reversion: About 40% of participants had prediabetes when the trial began. Prediabetes is when blood sugar levels are higher than normal, but not high enough for a type 2 diabetes diagnosis. By week 72 of the trial, blood sugar levels of a large majority (over 95%) normalized. 

SURMOUNT post hoc analysis 

Researchers conducted a post hoc analysis of the SURMOUNT clinical development program (SURMOUNT-1 is one study in this program). One group published their findings in Obesity, which is the journal of The Obesity Society. They highlighted how some tirzepatide participants self-reported real gains in physical function. This refers to the ability to perform everyday activities, such as walking and climbing stairs. Participants who began the study with physical limitations reported the most meaningful progress. 

Another group published their findings in Diabetes, Obesity and Metabolism. They asked, “What kind of weight loss did tirzepatide support?” They found approximately three-quarters of tirzepatide-driven weight loss stemmed from fat (74%). Lean mass made up the rest (26%), which includes muscle. 

Losing some lean mass is normal. Researchers noted that tirzepatide didn’t produce disproportionate lean mass loss. They did, however, emphasize how lifestyle changes, like diet and exercise, played a role. That’s why it’s important to have a care team that looks beyond numbers on the scale. 

TRIUMPH program

Retatrutide is earlier in its journey. In a 2023 phase 2 trial, also published in the New England Journal of Medicine, researchers followed 338 adults with obesity or overweight with a weight-related condition. None had diabetes. Over 48 weeks, participants on the highest dose (12 mg) lost an average of approximately 24% of their body weight. Those on placebo lost approximately 2%. 

Retatrutide has since moved into phase 3, a larger set of trials called the TRIUMPH program. In December 2025, TRIUMPH-4 reported meaningful weight loss outcomes for adults with obesity and knee osteoarthritis. Those on the highest dose (12 mg) of retatrutide lost an average of approximately 29% of their body weight over 68 weeks. Many reported less knee pain, too. TRIUMPH-1 (May 2026), a larger-scale trial of over 2,300 participants, reported average weight losses of up to approximately 28% over 80 weeks. 

Although promising, it’s worth keeping these outcomes in perspective: the TRIUMPH program is ongoing. We can’t make concrete conclusions yet. 

As of July 2026, TRIUMPH-5 is underway. It’s a head-to-head trial comparing tirzepatide and retatrutide in adults with obesity. No early outcomes have been released just yet. Its estimated completion date is December 2026, with insights following soon after. 

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When will retatrutide be available?

Retatrutide isn’t available outside of clinical trials. Currently, Eli Lilly is completing the comprehensive Chemistry, Manufacturing, and Controls (CMC) data package. The FDA requires this information as part of the The Biologics License Application (BLA), which is the form companies submit when asking to sell a drug on the public market. Depending on the outcomes, Eli Lilly plans to submit retatrutide in early 2027 for U.S. approval. 

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Should you wait for retatrutide or start Zepbound® now?

There’s no single right answer for everyone. This is a conversation between you and your doctor. Here are a few factors to consider before deciding:

• Current availability: Want to start sooner rather than later? Zepbound® is available by prescription today. Retatrutide currently isn’t available to the public. 
• FDA approval: If you’re navigating one of Zepbound®’s approved indications, like chronic weight management and OSA, the drug might be an appropriate next step. 
• Unique health profile: Looking at your full health picture, your doctor will determine the right path for you—whether that’s Zepbound®, waiting for retatrutide, or something else entirely. 

If weight loss is your goal but you’re not in a rush, waiting on retatrutide might make sense. Its early data is promising. But discuss this with your doctor, who will point you in the right direction for your body. 

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Navigating GLP-1 care with Maven Clinic

Zepbound® and retatrutide are both solid options, depending on what final trials say about retatrutide. Our specialists at Maven Clinic can help you decide on your next move. As specialists in both GLP-1 and women’s care, we guide you on the right path for your body, supporting sustainable long-term outcomes. 

Discover our approach to GLP-1 care. 

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FAQ

What’s the difference between retatrutide and tirzepatide?

Tirzepatide is a dual agonist, meaning it mimics two natural hormones: GLP-1 and GIP. Retatrutide is a triple agonist. It mimics GLP-1, GIP, and glucagon. 

Is retatrutide more effective than Zepbound® for weight loss?

It’s too soon to say for sure. Early results indicate retatrutide may offer greater weight loss benefits than Zepbound® (tirzepatide), although trials remain underway. Of the two, only Zepbound® is currently FDA-approved for chronic weight management.

When will retatrutide be FDA-approved?

There’s no confirmed timeline. Eli Lilly may submit retatrutide for FDA approval during or following phase 3 trials, which are currently underway as of 2026. 

Can you switch from Zepbound® to retatrutide once it's approved?

If retatrutide gains FDA approval, switching to it from Zepbound® may be on the table. But this is a conversation between you and your doctor.

Is retatrutide a GLP-3? 

“GLP-3” is a nickname for retatrutide, but it’s not an accurate classification. It refers to retatrutide’s role in mimicking three hormones: GLP-1, GIP, and glucagon. “Triple agonist” is more suitable. 

What are retatrutide’s benefits?

Retatrutide is undergoing clinical trials, so its benefits are not yet established. But early results are promising. A phase 2 trial indicates patients lose an average of approximately 24% of their body weight over 48 weeks.