Retatrutide vs. semaglutide: A head-to-head comparison
Looking for the ultimate weight loss medication? Discover the key differences between retatrutide and semaglutide to find out which is right for you.
Key highlights
- Semaglutide is a popular and effective GLP-1 receptor agonist used for diabetes management and weight loss in overweight or obese individuals. Retatrutide is still in clinical trials and is expected to be available in 2026 or later.
- Retatrutide appears to have more average weight loss (24.2%) vs. semaglutide (14.9%) but long-term safety and effectiveness are still being studied for retatrutide.
- Semaglutide works by mimicking the GLP-1 hormone to regulate blood sugar and reduce appetite, while retatrutide mimics three hormones—GLP-1, GIP, and GCG to potentially offer more comprehensive benefits for weight loss, blood sugar control, and metabolism.
- As personalized care becomes a central focus in healthcare, these medications provide new hope for individuals battling obesity and type 2 diabetes.
With 500 million people worldwide with type 2 diabetes and 890 million obese, scientists are working on new treatments to improve overall health and well-being.
Two of the most talked about treatments are retatrutide and semaglutide and both have impressive weight loss results.
Retatrutide is a new weight loss drug from Eli Lilly and has promising results in clinical trials but is not yet available. People are wondering if it will be better than semaglutide and tirzepatide.
Retatrutide vs. semaglutide: Which weight loss drug is better? Compare their mechanism, effectiveness, side effects, cost, availability, and pros and cons to make an informed choice.
What are retatrutide and semaglutide?
While semaglutide works by activating the GLP-1 receptor, retatrutide activates GLP-1, GIP, and GCG receptors, which may offer even more benefits.
Retatrutide
Retatrutide is a novel weight loss treatment, manufactured by Eli Lilly, to treat obesity and type 2 diabetes.
Retatrutide is still in clinical trials and isn’t available yet. While it’s still new, scientists are excited about its potential, as it has shown significant results in treating obesity. In rodent studies, retatrutide helped obese mice lose more weight than tirzepatide.
In a clinical trial, retatrutide showed major improvements in managing blood sugar levels. These results highlight its potential as a strong alternative to medications like semaglutide (Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro).
Retatrutide works like other weight loss and type 2 diabetes medications, but what makes it different is that it can target three receptors (triple agonist) at once:
- Gastric inhibitory polypeptide receptor (GIP)
- Glucagon-like peptide-1 receptor (GLP-1)
- Glucagon receptors (GCG)
This unique triple-action may make it more effective than GLP-1 and GLP-1/GIP medications. Retatrutide belongs to a new class of drugs called triple agonists. By activating three receptors, it helps with better glycemic control and effective weight loss by:
- Boosting insulin release and sensitivity
- Reducing glucagon to prevent excess glucose production
- Slowing down digestion (gastric emptying) and making you feel fuller (increased satiety levels), which helps you eat less (reduced calorie intake)
Semaglutide
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used to treat type 2 diabetes and help with weight loss. It’s available under the brand names Wegovy, Ozempic, and Rybelsus. Wegovy is FDA-approved for chronic weight management in obese and overweight patients. Ozempic and Rybelsus are prescription drugs approved for adults with type 2 diabetes.
Semaglutide belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists. It mimics a natural hormone called GLP-1, which helps control blood glucose by releasing insulin when you eat, lowering blood sugar. GLP-1 also slows down how fast food moves through your stomach (gastric emptying), making you feel full longer, and helps control appetite by lowering blood sugar levels and promoting weight loss.
Semaglutide helps control hunger by activating parts of the brain that regulate appetite. This makes you feel fuller and less hungry, helping you make healthier food choices and eat fewer calories. It also slows down how quickly food leaves your stomach, making you full longer and reducing cravings.
- Wegovy: Approved by the FDA on December 5, 2017, to lower blood sugar in people with type 2 diabetes and off-label for weight loss in people with obesity and overweight. It was also approved in 2024 for reducing the risk of serious heart problems in adults with obesity or overweight.
- Ozempic: Approved by the FDA on June 4, 2021, for chronic weight management in patients with obesity (body mass index of 30 or more) and overweight (body mass index of 27 or more) with a weight-related condition like cardiovascular disease, high blood pressure, or type 2 diabetes.
Retatrutide vs. semaglutide: Mechanisms of action
Both retatrutide and semaglutide help control blood sugar and aid in weight loss, but they work in slightly different ways:
Semaglutide belongs to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists. It mimics a natural hormone called GLP-1, which helps control blood glucose by releasing insulin when you eat, lowering blood sugar. GLP-1 also slows down how fast food moves through your stomach (gastric emptying), making you feel full longer, and helps control appetite by lowering blood sugar levels and promoting weight loss.
Semaglutide helps control hunger by activating parts of the brain that regulate appetite. This makes you feel fuller and less hungry, helping you make healthier food choices and eat fewer calories. It also slows down how quickly food leaves your stomach, making you full longer and reducing cravings.
Retatrutide also works by activating the GLP-1 and GIP receptors, but also targets the glucagon (GCG) receptor, making it a triple agonist. This extra action makes retatrutide a more advanced option for treating type 2 diabetes and obesity by helping your body release more insulin, curb your appetite, and burn more energy.
While semaglutide is a single agonist (GLP-1 agonist), retatrutide is a triple agonist meaning it targets three hormones: GLP-1, GIP, and GCG. While GLP-1 and GIP perform similar actions for blood sugar control and fat metabolism as semaglutide, retatrutide also activates GCG which primarily benefits gut health and nutrient absorption. This additional mechanism may promote weight loss even more by improving digestion, a broader and potentially more effective approach than semaglutide.
Retatrutide vs. semaglutide: Weight loss effectiveness
Retatrutide and semaglutide are different medications with different chemical makeups.
Retatrutide works by mimicking three hormones to help with weight loss and blood sugar control, while semaglutide only mimics one hormone.
Retatrutide seems to help with more weight loss than semaglutide. Studies show that people using semaglutide lose about 6 kg after 40 weeks, while those using retatrutide can lose around 20 kg.
In a 68-week clinical trial, participants on Wegovy (semaglutide) lost an average of 14.9% body weight compared to 2.4% in the placebo group. Studies have shown an average weight loss of 15% of body weight over 26-30 weeks, especially for people with a BMI of 30 or higher, or those with a BMI of 27 or higher and obesity-related health issues like type 2 diabetes.
Studies show semaglutide (Wegovy and Ozempic) reduces the risk of cardiovascular events like stroke and heart attack. It also improves how the body handles fat which means better cholesterol and triglycerides.
Eli Lilly finished their phase II trials for retatrutide and shared the results in June 2023. The 48-week trial focused on people with obesity or overweight, but not those with type 2 diabetes.
The study measured weight loss at 24 weeks and 48 weeks. Here are the average weight loss results based on the dose and timeline:
- 1 mg: 7.2% in 24 weeks and 8.7% in 48 weeks
- 4 mg: 12.9% in 24 weeks and 16.3% in 48 weeks
- 8 mg: 17.3% in 24 weeks and 23.9% in 48 weeks
- 12 mg: 17.5% in 24 weeks and 24.2% in 48 weeks
- Placebo: 1.6% in 24 weeks and 2.1% in 48 weeks
The retatrutide clinical trials are still ongoing, with a phase IV planned after the current phase III. If everything goes as planned, it may be approved by the FDA in 2026 or later.
Retatrutide vs. semaglutide: Side effects
Since retatrutide is still in clinical trials, it’s too soon to say how effective and safe it is overall. The trials have shown promising results for weight loss, but, like any medication, it may have side effects and other things to consider.
The Phase II trial for retatrutide reported some adverse events:
- A large percentage of participants (73% to 94%) reported side effects while taking retatrutide, especially in the higher 8-mg and 12-mg groups.
- The most common side effects were stomach issues like nausea, diarrhea, vomiting, reduced appetite, and constipation. These problems mostly happened during the dose increase phase and were usually mild to moderate. Starting with lower doses helped reduce the severity.
- There were slight increases in certain digestive enzymes, like amylase and lipase, but only one case of serious pancreatitis.
- People taking higher doses had a higher heart rate during the first 24 weeks, but it returned to normal afterward.
- No serious cases of low blood sugar or thyroid cancer were reported.
- Some people (7% of those on retatrutide, compared to 1% on placebo) had skin sensitivity, but these cases were not serious.
The common side effects of semaglutide are usually mild and may include:
- Dizziness
- Headache
- Tiredness
- Nausea
- Vomiting
- Stomach pain
- Diarrhea
- Bloating
- Constipation
Semaglutide can cause rare but serious side effects such as pancreatitis, gallbladder problems, changes in vision, allergic reactions, and kidney issues.
Since semaglutide and retatrutide have similar side effects including nausea, diarrhea, vomiting, and constipation, it is best to consult a healthcare provider before including them in your weight loss journey.
Retatrutide vs. semaglutide: Dosage and administration
Retatrutide is typically used in weekly doses of 1 mg, 2 mg, 4 mg, 8 mg and 12 mg. Retatrutide is administered as a once-weekly subcutaneous injection. The specific timing and dosage should be determined by a healthcare provider based on individual needs.
Semaglutide (Ozempic and Wegovy) come as pre-filled subcutaneous weekly injections that are injected under the skin of your stomach (abdomen), thigh, or upper arm. Both medications are injected once per week on the same day of the week and can be taken with or without food. Your healthcare provider will start these weight loss injections on the lower dose (0.25 mg weekly) and gradually increase the dose based on how you respond, your goals, and your tolerance for side effects.
Wegovy is available in five different pre-filled, single-dose syringes including 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg. Each pen contains one dose, so you’ll need four pens for a 30-day supply. Doctors usually start patients at 0.25 mg once weekly for 4 weeks and then the dose is gradually increased every 4 weeks until the maximum dose of 2.4 mg once a week is reached.
Ozempic is available in four different pre-filled, multi-dose syringe pen doses including 0.25 mg, 0.5 mg, 1.0 mg, and 2 mg. You can reuse the pen for a month but use a new needle each time. Your pharmacy will give you one pen and the needles. Each pen has four different doses which is a 30-day supply. The number of pens you get depends on your dose. The maximum dose is 2 mg once a week.
Both retatrutide and semaglutide are easy to use, with once-a-week injections making it simple to stick to the treatment plan compared to taking medication every day.
Retatrutide vs. semaglutide: Cost and availability
Retatrutide
- Availability: Retatrutide is in clinical trials and has not yet been FDA-approved. It’s being evaluated for weight loss and metabolic health but is not available to the public yet. Availability of retatrutide will depend on the completion of trials and FDA approval, which could take some time. It will be available by prescription only.
- Cost: Pricing and insurance coverage are unclear since it hasn’t yet been released.
Semaglutide
Availability: FDA-approved (Ozempic and Wegovy) and available by prescription for managing type 2 diabetes and chronic weight management. Requires a prescription.
Cost: The list price of Wegovy is $1,349.02 per month. If you have insurance coverage for Wegovy, your out-of-pocket cost will be based on the copay and deductible in your plan. The manufacturer, Novo Nordisk offers a Wegovy Savings Card program to help people save money with or without insurance. It helps those with insurance to reduce their out-of-pocket costs of Wegovy to as low as $0/month by providing financial assistance to cover a portion of the cost, making the medication more affordable for qualifying individuals. Ozempic is cheaper than Wegovy. Without insurance, Ozempic costs about $997.58 for a 28-day supply. Ozempic may be covered by insurance, but coverage can vary. Novo Nordisk offers an Ozempic savings program to help reduce the cost for eligible patients, which can significantly lower the cost if you have private or commercial insurance.
Retatrutide vs. semaglutide: Which one is right for you?
Both medications are very effective at controlling blood sugar levels and aiding in weight loss, with retatrutide showing a small advantage in trials, but semaglutide has more long-term data as it’s already been FDA-approved.
Retatrutide could be ideal for people looking for significant weight loss and better metabolic health once it’s available.
Retatrutide may be suitable for adults who:
- Have a body mass index (BMI) of 27 or higher
- Struggle with weight management despite diet and exercise efforts
- Have type 2 diabetes
- Do not have a personal or family history of certain medical conditions or allergies
Semaglutide may be suitable for adults who:
- Have a BMI of 30 or higher
- BMI of 27 or higher with weight-related conditions, such as type 2 diabetes, high blood pressure, or high cholesterol
- Struggle with weight management, mainly if you’ve had limited success with diet and exercise alone.
- Do not have personal or family histories of certain medical conditions or allergies.
Pros and cons: Retatrutide vs. semaglutide
Semaglutide pros
- Once-weekly injection: One primary advantage of semaglutide is that it’s taken once a week, making it easier to stick to than daily medications.
- FDA-approved: It is FDA-approved for type 2 diabetes, chronic weight management, and reducing the risk of serious heart problems in adults with obesity or overweight ensuring safety and efficacy for its intended use.
- Improves blood sugar control: It is highly effective in managing type 2 diabetes by improving insulin sensitivity and controlling blood sugar levels.
- Proven efficacy: Effective in helping with weight loss and managing blood sugar levels in people with type 2 diabetes.
- Widely available: Semaglutide is generally widely available, making it easier for people to obtain.
- Copay assistance programs: Novo Nordisk offers copay assistance programs to reduce the cost of medication for eligible patients, making it more accessible for many.
Semaglutide cons
- Side effects: The main drawbacks of semaglutide are possible stomach-related side effects like nuasea, diarrhea and vomiting, which can be bothersome for some people.
- Cost: Semaglutide can be expensive, especially without insurance coverage, making it less affordable for some people.
- Insurance hurdles: Some insurance plans may not cover the medication, or they may require additional steps or approvals, making it harder to access.
- Not for everyone: Not for people with certain medical conditions (gastrointestinal issues or pancreatitis) or those with a history or family history of thyroid cancer.
- Weekly dosing only: While the weekly injection is great for many, it may not be ideal for people who prefer daily medicines or are uncomfortable with injections.
- Long-term effects unknown: While the clinical trials look promising, the long-term safety and efficacy of semaglutide, especially for weight loss, is still being studied.
- Requires medical supervision: You’ll need to see your doctor regularly to monitor effectiveness and side effects.
Retatrutide pros
- Triple mechanism of action: Retatrutide targets GLP-1, GIP, and GCG, which could offer a more comprehensive approach to weight loss, blood sugar control, and metabolic health, potentially providing superior benefits over dual agonists like tirzepatide.
- Promising weight loss results: Early trials have shown significant weight loss. Some participants have lost up to 24% of their body weight.
- Improved gut health: GCG activation may help with gut health and nutrient absorption, adding an extra layer of benefit beyond just weight loss and blood sugar control.
- Potential for type 2 diabetes and obesity treatment: Retatrutide is being studied for its effectiveness in treating both type 2 diabetes and obesity, offering hope for broader use in metabolic health.
- Convenient once-weekly injection: Like other medication in this class, retatrutide is a once-a-week injection that is easier to adhere to than daily treatments.
- Fewer options: As a new triple agonist, retatrutide is an option for patients who haven’t responded positively to other weight loss or diabetes medications.
Retatrutide cons
- Still in clinical trials: Retatrutide is not approved yet and is still in trials so it’s not commercially available for general use.
- Unknown long-term safety: As it’s still in development, the long-term safety and efficacy of retatrutide have not been established.
- Potential side effects: Although the exact side effects are still unknown, clinical trials have shown that it may cause the same side effects as other medications in this class like nausea, vomiting, diarrhea, constipation, and stomach discomfort.
- High cost: Once approved, it will likely be costly like other popular weight loss drugs.
- Need for ongoing monitoring: Since it’s a new drug, patients may need more frequent monitoring by providers to ensure safety and efficacy which can be inconvenient.
Frequently asked questions (FAQs)
Is retatrutide better than semaglutide?
Retatrutide and semaglutide are both effective for weight loss and managing type 2 diabetes, but retatrutide may work better for some people because it targets three hormones related to appetite control. However, the best choice depends on individual responses and medical advice.
When will retatrutide be available?
Retatrutide is still in clinical trials and has not been approved yet. Depending on the approval process, it may become available in 2026 or later.
Can you switch from semaglutide to retatrutide?
Yes, you can switch from semaglutide to retatrutide, but it’s important to do so under the guidance of a healthcare professional.
Are these medications safe for long-term use?
Both semaglutide and retatrutide have shown safety in clinical trials, but long-term effects are still being studied. It’s important to use them under a doctor’s supervision to monitor for any potential issues over time.
Bottom line
Retatrutide is still in clinical trials, with early data suggesting significant weight loss potential, while semaglutide has FDA approval with proven efficacy and safety history.
Retatrutide and semaglutide are innovative medications showing promising potential for weight loss and improving metabolic health, particularly in managing obesity and type 2 diabetes.
Both semaglutide and retatrutide have the potential to transform weight loss treatment, with retatrutide possibly offering even greater results. However, their success depends on personalized care, where patients and healthcare providers work together to choose the best treatment.
Consult with your doctor to discuss whether retatrutide or semaglutide is right for you. Your doctor will determine the best treatment plan based on your weight loss goals, medical history, overall health, and individual response to medication.
