Zepbound vs. retatrutide: How these weight loss drugs compare

The weight-management medication landscape is rapidly changing, and you may soon find yourself wondering: In a matchup between Eli Lilly’s Zepbound® (tirzepatide) and retatrutide (currently under development by Lilly), which works best for weight loss? 

Although retatrutide is not yet available as a prescription weight loss drug, read up now and you’ll be well prepared for the coming Zepbound vs. retatrutide debate.

 Zepbound vs. retatrutide: How do they work?

Like Lilly’s other tirzepatide medication, Mounjaro®, Zepbound is a dual agonist that mimics GLP-1/GIP hormones and promotes weight loss by slowing digestion,  increasing satiety, and tamping down hunger. (GLP-1 is short for glucagon-like peptide-1. GIP is short for glucose-dependent insulinotropic polypeptide.) These two naturally occurring hormones help the body increase energy expenditure and regulate blood glucose levels and appetite, all contributing to weight loss.

That's in contrast to single-agonist medications like Novo Nordisk’s Wegovy® and Ozempic®, which stimulate the body’s GLP-1 receptors to slow digestion, causing people to feel fuller longer after eating. 

Retatrutide, which Eli Lilly is also developing as an obesity drug, is considered a triple hormone receptor agonist. That’s because it mimics the GLP-1 and GIP hormones and a third hormone called glucagon. The pancreas secretes glucagon to help maintain blood sugar levels, affecting hunger and satiety signals. Retatrutide is sometimes called a "triple G" drug because it aims to activate the body’s receptors for those three G-word hormones. 

Like several other weight-loss medications, it’s also being studied as a treatment for type 2 diabetes and is a once-weekly injection. 

How much weight can you lose with Zepbound (compared to retatrutide)?

The FDA approved Zepbound based on results from several clinical trials. In them, patients taking the highest weekly dose (15 mg) of Zepbound lost 48 pounds on average, while those taking the lowest dose (5 mg) lost on average 34 pounds (compared to 7 pounds on placebo) over 72 weeks. The average starting body weight was about 230 pounds.

The results from SURMOUNT-4, Lilly’s most recently published tirzepatide study, showed a 20.9% weight reduction within 36 weeks for those taking the maximum tolerated dose (10 mg to 15 mg a week), with an additional 6.7% weight loss over the next year.

Zepbound is FDA-approved for chronic weight management in people with obesity or a body mass index (BMI) of 30 or higher, and in those who are overweight (BMI of 27 or higher) who have at least one weight-related condition, such as high blood pressure or cholesterol. 

If you’re prescribed Zepbound, your Found provider will typically start you on the lowest dose to help your body get used to the medication and then increase your dosage over time. The dose strength is usually increased every four weeks to minimize uncomfortable side effects. (Note: Found’s clinicians work with patients to determine the best option, but the ultimate decision about whether a patient is qualified for a medication rests with the provider.)

And retatrutide? During a 48-week phase 2 obesity trial, patients on weekly doses of retatrutide (8 mg and 12 mg) had average body weight losses of 22.8% and 24.2%, respectively. These results suggest retatrutide may prompt even greater weight loss than other weight-loss medications, including Zepbound. However, research on retatrutide is ongoing, and more trials are needed to evaluate its safety and efficacy before the FDA will consider it for approval. 

‍When will retatrutide be available?

Eli Lilly hasn’t shared a proposed timeline for making retatrutide available, and clinical trials required for FDA approval are ongoing. According to industry reports, Eli Lilly’s phase 3 trial of retatrutide is expected to conclude in early 2026. Given the typical timeline for FDA approval,  the medication may not be on the market until 2027.

Zepbound vs. retatrutide: How much do they cost?

The manufacturer’s list price for a 28-day supply of Zepbound is $1,059 for four prefilled, single-use injection pens. However, what you are charged at the pharmacy may be higher, and what you ultimately pay may be lower if you have insurance coverage or use a savings card or coupon to reduce your out-of-pocket cost.

Because retatrutide is not yet an FDA-approved medication, its cost hasn’t been established.

‍How do side effects and warnings compare for Zepbound vs. retatrutide?

As with any prescription medication, Zepbound has some known potential side effects. The most common side effects for Zepbound (tirzepatide) include:

• Constipation
• Decreased appetite
• Diarrhea
• Fatigue
• Gastroesophageal reflux disease
• Hair loss
• Indigestion
• Injection-site reactions
• Nausea
• Stomach pain
• Vomiting

In tirzepatide’s clinical trials, researchers noted that when doses increased, side effects, like nausea and diarrhea occurred. Over time, as patients adjusted to the increased dose, the side effects typically subsided. Patients taking Zepbound should tell their health care provider if they experience severe stomach problems that won’t go away, including abdominal bloating or pain, acid reflux, a feeling of fullness after eating just a few bites of food, nausea, and vomiting (including vomiting undigested food eaten a few hours earlier). These may be symptoms of gastroparesis (stomach paralysis). 

Like GLP-1 receptor agonists, tirzepatide also has an FDA-mandated “black box” warning for patients with a personal or family history of medullary thyroid cancer and those who have multiple endocrine neoplasia syndrome type 2. They should not take tirzepatide. Read more detailed side effects and risks on our dedicated Zepbound medication page. 

Researchers are still studying the side effects and risks of retatrutide. But the most frequently reported adverse effects in clinical trials for it thus far have been gastrointestinal issues, including nausea, diarrhea, vomiting, and constipation.

‍Which is better for weight loss: Zepbound or retatrutide?

That’s a tricky question since we still don't have all the info on retatrutide, including what doses will be available and how those will compare to Zepbound. Also, individual results vary with any medication. For example, you may see significant weight loss on Zepbound, while a friend taking the same drug and the same dosage for the same amount of time may experience modest weight loss or even none at all.

These variables are why medications are a tool—but not the only one—utilized at Found. Our program focuses on personalization to support you with the right clinical treatment for your unique needs. To build treatment plans, our clinicians use a metabolic health assessment called MetabolicPrint™ that uncovers the root causes of weight challenges to create a foundation for a personalized treatment plan.

In addition, Found offers specialists trained in obesity medicine, as well as professionals who can help you integrate medication with healthy lifestyle behaviors, and a community of fellow subscribers who provide support and encouragement to help make sustainable changes. These offerings create a multi-layered approach to weight loss that is tailored to each individual. To start your journey with Found, take our quiz.

‍About Found

Found is among the largest medically-supported telehealth weight care clinics in the country, having served more than 250,000 members to date. To discover your MetabolicPrint™ and start your journey with Found, take our quiz.

About GLP-1s and tirzepatide prescriptions

GLP-1 and tirzepatide prescriptions, filled through your local pharmacy, are now available as part of Found's weight-loss toolkit. GLP-1 medicines are not included in the cost of the Found subscription. While these medications can be effective for weight loss, like all medicines, they are not clinically appropriate for everyone. Eligibility for these drugs is based on a thorough evaluation of your medical history and lab work. If GLP-1s or tirzepatide are not appropriate for you, our providers will work with you to determine an effective medication for your health profile.