Retatrutide vs. semaglutide for weight loss

Retatrutide and semaglutide are medications for weight loss, type 2 diabetes, and other conditions. Semaglutide is already approved and available by prescription, while retatrutide is not — but it may be soon. Below, we catch you up to speed on the differences, similarities, and everything else you need to know about retatrutide vs. semaglutide.

Retatrutide is an investigational injectable medication for weight loss currently being studied by Eli Lilly. It has not been approved by the US Food and Drug Administration (FDA).

Semaglutide is made by Novo Nordisk. It is available as a daily pill or weekly injection under two brand names:

• Wegovy, which is FDA-approved for weight loss in adults and adolescents with obesity (or in adults with overweight and a weight-related health condition). It is also approved to lower cardiovascular risk in adults with heart disease and obesity or overweight and treat fatty liver disease in certain people.

• Ozempic, which is FDA-approved to lower blood sugar levels in adults with type 2 diabetes. It is also approved to lower cardiovascular risk in adults with type 2 diabetes and heart disease, and to reduce the risk of kidney decline in adults with type 2 diabetes and chronic kidney disease.

Wegovy and Ozempic are both meant to be used in combination with lifestyle changes, such as diet and exercise. 

*Retatrutide dosing shown here reflects doses studied in clinical trials. Because retatrutide is still investigational, dosing has not been finalized for clinical use. Any approved schedule would be determined during FDA review.

**Terms and restrictions may apply for certain doses

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Based on the available trial data, retatrutide may produce greater average weight loss than semaglutide. However, the two have not been directly compared in a head-to-head trial, and retatrutide is not yet approved. 

Meanwhile, semaglutide is already approved for weight loss (along with other conditions like type 2 diabetes and fatty liver disease). It has a well-established safety record based on large-scale clinical trials and nearly a decade of real-world experience since its initial FDA approval in 2017. Retatrutide is still being studied in clinical trials. The commercial availability of retatrutide will depend on the results of those trials and FDA review.

Based on data from separate clinical trials, both retatrutide and semaglutide can produce significant weight loss. However, retatrutide appears to produce higher average weight loss than semaglutide, as well as any other currently available weight loss medication.

In less than a year and a half, people taking retatrutide have lost an average of 71 pounds. Here’s a look at some recent weight loss results for retatrutide:

• In a phase 3 TRIUMPH-4 trial for obesity and knee osteoarthritis, people taking 12 mg of retatrutide lost an average of 28.7% of their body weight in 68 weeks (about a year and four months).

• In a phase 2 clinical trial for obesity, people taking 12 mg of retatrutide lost an average of 17.5% of their body weight in 24 weeks and 24.2% in 48 weeks (about eleven months).

• In a phase 2 clinical trial for type 2 diabetes, people taking 12 mg of retatrutide achieved significant blood sugar reductions and lost an average of 17% of their body weight in 36 weeks (about eight months). 

In less than a year and a half, people taking semaglutide 2.4 mg have lost up to 14.9% of their body weight. People tend to lose more weight on the higher-dose versions of semaglutide prescribed for weight management, such as the Wegovy pill and injection. Here’s a look at some recent weight loss results for semaglutide:

• In a phase 3 clinical trial of people with obesity, people taking the Wegovy injection (2.4 mg injectable semaglutide) lost an average of 14.9% of their body weight in 68 weeks (about a year and four months). 

• In a clinical trial of people with obesity, people taking the Wegovy pill (25 mg oral semaglutide) lost an average of 13.6% of their body weight in 64 weeks (about a year and three months). 

• In a clinical trial of people with type 2 diabetes, people taking the 2.4 mg Wegovy injection lost an average of 9.6% of their body weight in 68 weeks. 

• In a clinical trial of people with type 2 diabetes, people taking the Wegovy pill had significantly lower blood sugar levels and lost an average of 7.3% of their body weight in 52 weeks. 

• In the STEP UP clinical trial for obesity, people taking the Wegovy HD 7.2 mg weekly injection lost an average of 18.7% of their body weight in 72 weeks, while those using Wegovy 2.4 mg lost 15.6% on average. 

By comparison, the people who took a placebo in any of the trials listed above lost around 2%–3% of their body weight.

Retatrutide and semaglutide work similarly for weight loss and blood sugar control. Both mimic a gut hormone called GLP-1 (glucagon-like peptide 1). What makes retatrutide unique among GLP-1 medications currently available is that it also mimics two additional hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG).

Retatrutide

If approved, retatrutide could be the first triple hormone receptor agonist. It’s so-called because it mimics three naturally occurring hormones to produce weight loss and control blood sugar levels:

• GLP-1 (glucagon-like peptide 1): This peptide may support weight loss by slowing digestion to promote feelings of fullness. It also can reduce appetite signals in the brain, which can lead to eating less. Finally, it boosts insulin production while reducing  glucagon levels, which may help prevent blood sugar spikes after meals.

• GIP (glucose-dependent insulinotropic polypeptide): This gut hormone can enhance the effects of GLP-1 by slowing digestion and encouraging the release of insulin. It may also promote fat burning.  

• Glucagon: This hormone also increases the body’s metabolic rate and fat-burning capacity. Research suggests that the combination of all three hormones may produce greater weight loss than single-receptor agonists like semaglutide.

Semaglutide 

Unlike retatrutide, semaglutide is a single hormone receptor agonist. It mimics the body's natural GLP-1 to slow digestion, reduce appetite, and increase insulin production while reducing glucagon levels.

Clinical trial data indicate that semaglutide works well for weight loss and blood sugar control, though it may not produce the same level of weight loss as retatrutide.

Because both are GLP-1 receptor agonists, retatrutide and semaglutide may share similar side effects, which include:

• Nausea

• Diarrhea

• Vomiting

• Constipation

Typically, GLP-1 receptor agonists cause mild to moderate gastrointestinal side effects, which are most common when starting the medication or increasing the dose. Retatrutide's full side effect and risk profile won't be known until it passes FDA review; the side effects above were most commonly reported in clinical trials. 

As a GLP-1 receptor agonist, retatrutide may carry similar risks to semaglutide, which include:

• Acute pancreatitis

• Diabetic retinopathy complications (diabetes-related vision changes)

• Hypoglycemia (low blood sugar), especially when used with insulin

• Kidney or gallbladder issues

• Severe gastrointestinal reactions

• Allergic reactions

• Pulmonary aspiration during general anesthesia or deep sedation

All GLP-1 receptor agonists carry a boxed warning for thyroid tumors based on animal studies. Whether this effect occurs in humans is not yet known. People with a personal or family history of thyroid cancer should not take semaglutide, and this may apply to retatrutide as well, pending FDA review.

Semaglutide and retatrutide both follow a gradual dose escalation schedule to help the body adjust to the medication. A healthcare provider will typically prescribe a low starting dose and gradually increase it over several weeks.

*Retatrutide dosing shown here reflects doses studied in clinical trials. Because retatrutide is still investigational, dosing has not been finalized for clinical use. Any approved schedule would be determined during FDA review.

Semaglutide’s dosing schedule is established by the FDA-approved prescribing label for each brand and form of semaglutide. Retatrutide dosing varied depending on the treatment people were assigned to in the clinical trials. Its dosing hasn’t been finalized for clinical use, and any approved schedule would be determined at the time of FDA review.

In clinical trials, retatrutide was administered via subcutaneous (under-the-skin) injection, similar to injectable semaglutide. With these weight loss injections, the medication is injected into the thigh, abdomen, or upper arm, rotating the injection site each week.

Oral semaglutide is taken daily in the morning on an empty stomach, at least 30 minutes before food, water, and other medications.

Retatrutide's price has not been announced, as the drug has not yet received FDA approval. The cost of semaglutide without insurance can range from $149 to over $1,000 per month. With qualifying private insurance and the manufacturer savings offer, semaglutide may be available for as low as $25 per month.

Cost of retatrutide

• Retatrutide’s price is currently unknown as it has not yet been FDA approved.

• You may be able to get retatrutide for free if you participate in a clinical trial.

Cost of semaglutide

Here’s a look at the pricing for the different brand-name versions of semaglutide: 

• Wegovy pen and pill both have a list price of $1,349.02 per month. Cash payers can get Wegovy on Ro for $149–$399 per month, depending on dose and form (if prescribed)). If you have private insurance coverage for Wegovy, the manufacturer savings offer can lower the cost of Wegovy to $25 for a one-month Rx.

• Ozempic has a list price of $1,027.51 per month. Cash payers can get Ozempic on Ro for $900–$1,100 per month without insurance. If your private insurance covers Ozempic, the manufacturer offer can lower Ozempic’s cost to $25 for up to a three-month Rx.

Right now, the answer is straightforward: semaglutide is the only option currently available. Both oral and injectable forms of semaglutide are FDA-approved and commercially available, with an established safety record from clinical trials and real-world use.

Retatrutide may eventually become available, but Eli Lilly is still conducting clinical trials on the investigational weight loss drug. Depending on the results of those trials (which are  expected later this year), the drug manufacturer may choose to apply for FDA review.

Anyone interested in a GLP-1 receptor agonist like semaglutide should speak with a healthcare provider. A provider can help determine whether semaglutide is appropriate, discuss individual health goals, and provide updates when (or if) retatrutide becomes available.

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Semaglutide and retatrutide are both GLP-1 receptor agonists that work similarly in the body, but they differ in important ways.

• Semaglutide is already available and FDA-approved for weight loss, type 2 diabetes, and other conditions. 

• Retatrutide is still being studied for weight loss, type 2 diabetes, and other conditions.

• While the two have not been compared directly, early clinical trial data suggests retatrutide produces greater average weight loss — 28.7% vs. semaglutide's 14.9% at 68 weeks.

• Retatrutide is a weekly injection, while semaglutide is available as both a weekly injection or a daily pill.

• Both medications may have similar side effects, risk profiles, and dosing schedules.