Retatrutide vs tirzepatide for weight loss
The battle of the weight loss drugs: Retatrutide vs. tirzepatide. Which one is better?
Key highlights
- Tirzepatide is FDA-approved for type 2 diabetes and weight loss. Retatrutide is still in clinical trials and is expected to be available in 2026 or later.
- Retatrutide looks to have more average weight loss (24.2%) vs. Tirzepatide (26.6%) but long-term safety and effectiveness are still being studied for retatrutide.
- Both are new drugs in the rapidly changing world of weight loss and metabolic health. Tirzepatide is a dual GLP-1/GIP agonist, and retatrutide is a triple-hormone-receptor agonist for more comprehensive metabolic benefits including gut health.
- With personalized care being a core focus in healthcare today, these medications offer hope for those with obesity and type 2 diabetes.
Type 2 diabetes affects over 500 million people worldwide, and obesity affects more than 890 million. Because these conditions are so common, scientists are working on better treatments to help people improve their overall health.
Two of the most talked-about treatments are retatrutide and tirzepatide, both showing significant results in weight management.
Retatrutide, a new weight loss drug from Eli Lilly, shows promising results in clinical trials, but it’s not yet available. People are curious if it will be more effective than current treatments like semaglutide and tirzepatide.
Retatrutide vs. Tirzepatide: Which is right for you? Compare these cutting-edge weight loss medications head-to-head, exploring their mechanisms, benefits, side effects, and more.
What are retatrutide and tirzepatide?
Like retatrutide, tirzepatide (Mounjaro, Zepbound) is an innovative treatment that has gained attention for its effective results in controlling blood sugar levels and weight management. While tirzepatide works by activating the GLP-1 and GIP receptors, retatrutide activates GLP-1, GIP, and GCG receptors, which may offer even more benefits.
Retatrutide
Retatrutide is a new 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:
- GIP (gastric inhibitory polypeptide) receptor
- GLP-1 (glucagon-like peptide-1) receptor
- GCG (glucagon) receptor
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 control blood sugar and supports 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)
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 two points: 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.
Tirzepatide
Tirzepatide, also known by the brand names Mounjaro and Zepbound, is an FDA-approved dual-action GLP-1/GIP receptor agonist made by Eli Lilly.
Zepbound was FDA-approved in 2023 for long-term weight management in adults with obesity (with a body mass index of 30 or higher) and overweight (with a body mass index of 27 or higher) with at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol.
Mounjaro was FDA-approved in 2022 for managing blood sugar levels in adults with type 2 diabetes.
Tirzepatide has shown a significant reduction in HbA1c levels, a key measurement reflecting average blood glucose levels over 3 months.
Tirzepatide works by mimicking two hormones, glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, that help your pancreas release more insulin. This dual action boosts insulin release, helps manage fat storage, makes you feel fuller longer, reduces appetite, and helps you lose weight faster. It also helps with gastric emptying, slowing the time it takes for the stomach to empty, and interacts with areas in the brain that signal satiety.
Studies have also shown that tirzepatide provides improvements in people with obstructive sleep apnea (OSA) and Zepbound was recently approved by the FDA for this indication.
Retatrutide vs. tirzepatide: Mechanisms of action
Both retatrutide and tirzepatide help control blood sugar and aid in weight loss, but they work in slightly different ways:
- Tirzepatide: Tirzepatide works by activating the GLP-1 and GIP receptors in the body, helping to control blood sugar, reduce appetite, and make you feel fuller for longer, even with less food.
- Retatrutide: 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.
Tirzepatide and retatrutide are both weight loss medications but they work differently because of their unique mechanisms of action. Tirzepatide is a dual agonist meaning it targets two hormones: GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide). GLP-1 helps control blood sugar by improving insulin sensitivity and reducing appetite, GIP helps insulin secretion and fat metabolism. This combination controls blood sugar, reduces appetite, and promotes weight loss.
Retatrutide is a triple agonist meaning it targets three hormones: GLP-1, GIP, and GCG. While GLP-1 and GIP do similar things for blood sugar control and fat metabolism as tirzepatide, 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 Tirzepatide.
Retatrutide vs. tirzepatide: Weight loss and metabolic benefits
Both retatrutide and tirzepatide show promising weight loss results in a short time. In the tirzepatide trial, participants lost an average of 6.9% of their weight after 12 weeks, while retatrutide participants lost 7.2% at the lowest dose after 24 weeks.
After 84 weeks, tirzepatide participants lost an average of 26.6%, while those on the highest dose of retatrutide lost around 24.2% over 48 weeks.
As of now, there have not been direct head-to-head clinical studies comparing retatrutide and tirzepatide. However, there are individual studies for each medication showing their efficacy and researchers are closely examining their results in various settings.
Retatrutide
- Weight loss: In clinical trials, participants lost up to 24.2% of their body weight over 48 weeks.
- Blood sugar control: Significant reductions in HbA1c levels, showing better control of blood sugar.
- Clinical trials: Ongoing studies show promising results for weight reduction and blood sugar control.
Tirzepatide
- Weight loss: Clinical trials showed a weight loss of up to 22.5%.
- Blood sugar control: The majority of participants reached their target HbA1c levels.
- Clinical trials: Proven efficacy in both diabetic and non-diabetic individuals.
Retatrutide vs. tirzepatide: 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.
Tirzepatide’s common side effects include:
- Nausea
- Vomiting
- Diarrhea
- Stomach pain
- Decreased appetite
- Risk of low blood sugar
- Constipation
Serious side effects of tirzepatide can include pancreatitis (inflammation of the pancreas), gallbladder problems, kidney problems, and severe allergic reactions. It can also cause low blood sugar, especially if you are taking other diabetes medications, so monitor your blood sugar levels regularly. Some people may have mild reactions at the injection site, like redness or irritation.
Since tirzepatide 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. tirzepatide: Dosage and administration
- Retatrutide: It is a once-weekly subcutaneous injection, available in weekly doses of 1 mg, 2 mg, 4 mg, 8 mg and 12 mg.
- Tirzepatide: It is also a once-weekly subcutaneous injection, available in weekly doses of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg.
Both 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. tirzepatide: Cost and availability
Retatrutide
- Availability: Retatrutide is in clinical trials and has not been FDA-approved. It’s being evaluated for weight loss and metabolic health but is not available to the public yet. The 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.
Tirzepatide
- Availability: FDA-approved (Mounjaro and Zepbound) and available by prescription for managing type 2 diabetes and chronic weight management. Requires a prescription.
- Cost: Usually covered by insurance for diabetes treatment, but coverage for weight loss may vary. It costs between $1,000-$1,300 per month. Eli Lilly offers copay assistance programs to reduce costs, sometimes as low as $25 per month for eligible patients.
Pros and cons: retatrutide vs. tirzepatide
Along with possible side effects from retatrutide and tirzepatide, rapid weight loss can cause other problems.
Losing weight too quickly can lead to:
- Muscle loss: You may lose muscle along with fat, which can make it harder to keep the weight off.
- Nutritional deficiencies: Losing weight fast can lead to a lack of essential nutrients.
- Ozempic face or Ozempic butt: These terms describe sagging skin or a deflated look from fast weight loss.
- Hair loss: Rapid weight loss can cause temporary hair thinning.
Tirzepatide pros
- Effective for weight loss: Tirzepatide has shown significant weight loss results, with some patients losing over 20% of their body weight, especially in people with obesity.
- Improves blood sugar control: It is highly effective in managing type 2 diabetes by improving insulin sensitivity and controlling blood sugar levels.
- Dual mechanism of action: By targeting both GLP-1 and GIP hormones, it helps control appetite, improve metabolism, and enhance insulin release.
- Once-weekly injection: It only requires once-a-week injections, making it convenient compared to daily treatments.
- Potential cardiovascular benefits: Some studies suggest it may have positive effects on heart health due to improved metabolic markers.
- FDA-Approved: It is FDA-approved for type 2 diabetes, chronic weight management and obstructive sleep apnea (OSA), ensuring safety and efficacy for its intended use.
- Copay assistance programs: Eli Lilly offers copay assistance programs to reduce the cost of medication for eligible patients, making it more accessible for many.
Tirzepatide cons
- Side effects: Nausea, vomiting, diarrhea, injection site reactions. These side effects can be a real nuisance for some people.
- Cost: Tirzepatide can be expensive without insurance, costing $1,000 to $1,200 per month. With insurance, copays can be high for some.
- Not for everyone: Not for people with certain medical conditions (gastrointestinal issues or pancreatitis) or those with a history of thyroid cancer. Use with caution if you have 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 good, the long-term safety and efficacy of tirzepatide, 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 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 which 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 weight loss and diabetes 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.
Retatrutide vs. tirzepatide: Which 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 tirzepatide 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. Tirzepatide works well for people managing type 2 diabetes and wanting to lose weight.
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
Tirzepatide 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
Retatrutide and tirzepatide: FAQs
Is retatrutide better than tirzepatide for weight loss?
Retatrutide and tirzepatide are both effective for weight loss, 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 tirzepatide to retatrutide?
Yes, you can switch from tirzepatide 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 tirzepatide 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 tirzepatide has FDA approval and proven efficacy and safety history.
Retatrutide and tirzepatide are innovative medications showing promising potential for weight loss and improving metabolic health, particularly in managing obesity and type 2 diabetes.
Tirzepatide is already making waves in weight loss and type 2 diabetes treatment, with its dual receptor approach offering great potential for blood sugar regulation and appetite control.
Retatrutide, with its triple agonist action, could set a new benchmark in weight loss and metabolic health by aiding in weight loss and blood sugar control and also improving gut function and nutrient absorption.
Consult with your doctor to discuss whether retatrutide or tirzepatide is right for you. Your doctor will determine the best treatment plan based on your weight loss goals, medical history, and individual response to medication.
