As the search for effective weight loss solutions continues, Retatrutide, Eli Lilly’s new weight loss medication, has emerged as a potential new superstar. While it is not yet available on the market, ongoing Retatrutide clinical trials have shown remarkable results, leaving everyone wondering whether Retatrutide can outperform existing treatments that are semaglutide and tirzepatide based.
This article is for educational purposes only and is not intended as medical advice, diagnosis, or treatment. Always consult a licensed healthcare provider before making decisions about medications or treatment plans.
Active Ingredient: Semaglutide
Semaglutide is a GLP-1 receptor agonist only. It mimics the hormone GLP-1, which helps regulate blood sugar and appetite.
| Brand Name | Manufacturer | Route | FDA-Approved Use | FDA Approval Year |
|---|---|---|---|---|
| Ozempic | Novo Nordisk | Injectable (weekly) | Type 2 diabetes; Cardiovascular risk reduction | 2017 |
| Wegovy | Novo Nordisk | Injectable (weekly) | Chronic weight management | 2021 |
| Rybelsus | Novo Nordisk | Oral (daily tablet) | Type 2 diabetes | 2019 |
Active Ingredient: Tirzepatide
Tirzepatide is a dual agonist — it activates GLP-1 receptors and GIP (glucose-dependent insulinotropic polypeptide) receptors. The added GIP activity may enhance weight loss and blood sugar control compared to GLP-1–only drugs.
| Brand Name | Manufacturer | Route | FDA-Approved Use | FDA Approval Year |
|---|---|---|---|---|
| Mounjaro | Eli Lilly | Injectable (weekly) | Type 2 diabetes | 2022 |
| Zepbound | Eli Lilly | Injectable (weekly) | Chronic weight management | 2023 |
Active Ingredient: Retatrutide
Retatrutide is an experimental triple receptor agonist—activating GLP-1, GIP, and glucagon receptors—designed to enhance weight loss and metabolic control.
| Brand Name | Manufacturer | Route | Potential FDA-Approved Use | FDA Approval Year |
|---|---|---|---|---|
| — | Eli Lilly and Company | Injectable (weekly) | Investigational use for obesity, type 2 diabetes, nonalcoholic fatty liver disease | Not yet approved (In clinical trials Phase II/III) |
How does Retatrutide work for weight loss?
Retatrutide’s mechanism of action is similar to other weight loss and type 2 diabetes medications. What sets Retatrutide apart is its unique ability to engage three receptors simultaneously:
- GIP (Gastric Inhibitory Polypeptide) receptor
- GLP-1 (Glucagon-Like Peptide-1) receptor
- GCG (Glucagon) receptor
This puts Retatrutide into a new medication class known as triple agonists. By activating these three receptors, Retatrutide effectively improves glucose control and supports weight loss by:
- Enhancing insulin secretion and sensitivity.
- Suppressing glucagon release to prevent excessive glucose production.
- Slowing gastric emptying and promoting satiety, which can help reduce caloric intake.
Retatrutide clinical trials and preliminary results
Eli Lilly, the manufacturer of Retatrutide, completed their Phase II trials and released results in June 2023. This phase was a 48-week trial focusing on individuals with obesity, or overweight with weight-related conditions—except type 2 diabetes.
The results of the study were evaluated at two key points: halfway through the trial at 24 weeks and again at the conclusion of the trial at 48 weeks. The chart below shows the Retatrutide weight loss results based on the dose and duration:
| Dosage | 24-Week Results | 48-Week Results |
| 1 mg | 7.2% | 8.7% |
| 4 mg | 12.9% | 16.3% |
| 8 mg | 17.3% | 23.9% |
| 12 mg | 17.5% | 24.2% |
| Placebo | 1.6% | 2.1% |
The Retatrutide clinical trials are still underway with a planned Phase IV beyond the current Phase III. If all goes well, FDA-approval and release will likely not happen until 2026 or beyond.
Retatrutide vs Semaglutide
Retatrutide is a triple agonist medication in development that activates three receptors—GIP, GLP-1, and GCG. Semaglutide (Ozempic, Wegovy) is a single agonist, specifically a GLP-1 medication.
Semaglutide has been on the market for some time and has shown clinically significant weight loss results, earning it FDA approval under the brand name Wegovy. Retatrutide is still in development.
While semaglutide effectively aids in weight loss by improving appetite control and glucose regulation, Retatrutide’s unique triple-action approach may offer enhanced benefits. With Retatrutide clinical trials still ongoing, there’s no way to tell which medication will be the better choice.
Retatrutide vs semaglutide results
Both Retatrutide and semaglutide have been shown to result in clinically significant weight loss. In semaglutide’s 68-week trial, half of the participants lost 15% of their body weight, while one-third lost 20%.
With Retatrutide , weight loss was achieved in a much shorter time period. Participants on the higher doses of Retatrutide lost an average of 17% of their body weight in just 24 weeks, with weight loss continuing to progress to 23-24% by the 48-week mark.
Retatrutide vs tirzepatide
Like Retatrutide , tirzepatide (Mounjaro, Zepbound) was a first-of-its-kind treatment that has caught a lot of attention for its results. Another Eli Lilly medication, tirzepatide is a dual-agonist activating both the GLP-1 and GIP receptors. By activating the GLP-1, GIP, and GCG receptors, Retatrutide has the potential to offer even more benefits.
Tirzepatide is relatively new to market, only gaining FDA approval for weight loss (under Zepbound) in November 2023. Many insurance companies have yet to add tirzepatide to their formulary, but will likely do so in the next year.
Retatrutide vs tirzepatide results
Retaturitide and tirzepatide both show promising weight loss results in a short period. During the tirzepatide trial, participants experienced an average weight loss of 6.9% after 12 weeks. Retatrutide showed a 7.2% weight loss at the lowest dose over 24 weeks. Remember that a 5% weight loss can show health improvements for those with obesity.
After 84 weeks, tirzepatide participants achieved an impressive mean weight loss of 26.6%. The Retatrutide participants lost around 24.2% over 48 weeks at the highest dose.
Retatutride vs Tirzepatide vs Semaglutide: A Comparison
| Medication | Weight Loss | Duration | Type of Receptor Agonist | FDA-approval for Weight Loss |
| Retatrutide | 24.2% | 48 weeks | Triple | Trials Ongoing |
| Semaglutide | 20% | 68 weeks | Single | Yes, under Wegovy |
| Tirzepatide | 26.6% | 84 weeks | Dual | Yes, under Zepbound |
Is Retatrutide safe and effective for weight loss?
Since clinical trials for Retatrutide are still ongoing, it’s too early to provide a definitive answer regarding its overall effectiveness and safety.
In clinical trials, Retatrutide has shown promising results for weight loss, but like any medication, it comes with potential side effects and considerations. Phase II trial results did include data on adverse events:
- A significant percentage of participants (73% to 94%) reported adverse events while taking Retatrutide , particularly in the higher 8-mg and 12-mg groups.
- The most commonly experienced side effects were gastrointestinal issues, including nausea, diarrhea, vomiting, and constipation.
- Digestive side effects mainly occurred during the dose escalation phase and were mostly mild to moderate in severity—lower starting doses seemed to lessen this severity.
- There were slight increases in certain digestive enzyme levels, such as amylase and lipase. But there was only one reported serious case of pancreatitis.
- Participants taking higher doses of Retatrutide experienced an increase in heart rate during the first 24 weeks, after which it decreased.
- No serious cases of low blood sugar or significant complications like thyroid cancer were reported among participants.
- Some individuals (7% of those on Retatrutide compared to 1% on placebo) experienced skin sensitivity, but these cases were not serious.
Downsides of Rapid Weight Loss
In addition to potential side effects from the medication, it’s important to consider the implications of rapid weight loss. Yes, Retatrutide shows clinically significant results in as little as 24 weeks, but losing weight too quickly can lead to other issues.
You’ll need to consider issues like:
- Muscle Loss: Rapid weight loss often results in the loss of lean muscle mass along with fat. This can decrease strength and metabolism, making it harder to maintain weight loss. You’ll need to try and prevent muscle loss.
- Nutritional Deficiencies: Losing weight too quickly may lead to inadequate nutrient intake, which can result in deficiencies.
- “Ozempic Face” or “Ozempic Butt”: These terms refer to changes in facial and body appearance due to significant weight loss, often leading to sagging skin or a deflated look.
- Telogen Effluvium (TE): This is a temporary form of hair loss triggered by rapid weight loss or significant trauma. It occurs when hair follicles enter a resting phase and may lead to noticeable thinning of hair.
Conclusion
Retatrutide is still undergoing clinical trials and probably won’t be available until at least 2026. If you’re ready to kick off your weight loss journey now, don’t worry—there are plenty of effective options out there!
Heally can connect you to a knowledgeable doctor who can help you find the best way forward. You don’t have to navigate this alone; let’s find the right solution together! Register today!
Sources
- New England Journal of Medicine: Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
- New England Journal of Medicine: Once-Weekly Semaglutide in Adults with Overweight or Obesity
- Eli Lilly: News Release: Lilly’s phase 2 retatrutide results published in The New England Journal of Medicine
- Clinical Trials Arena: Eli Lilly infiltrates anti-obesity market as Phase III trial for retatrutide begins
- Eli Lilly: News Release: Lilly’s tirzepatide shows additional 21.1% weight loss after 12 weeks of intensive lifestyle intervention, for a total mean weight loss of 26.6% from study entry over 84 weeks
- FDA Label: OZEMPIC (Semaglutide Injection) Medication Guide
- FDA Label: WEGOVY (Semaglutide Injection) Medication Guide
- FDA Label: RYBELSUS (Oral Semaglutide) Medication Guide
- FDA Label: MOUNJARO (Tirzepatide Injection) Medication Guide
- FDA Label: ZEPBOUND (Tirzepatide Injection) Medication Guide
Important Medical Information and Disclaimers
Medical Disclaimer
This article,“How does GLP-1RAs work to improve PCOS in women,” is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider regarding any questions you may have about a medical condition, medication, or treatment plan. Never ignore professional medical advice or delay seeking it because of something you have read here.
GLP-1 receptor agonists such as semaglutide (marketed under brand names Ozempic®, Wegovy®, and Rybelsus®) and the dual GIP/GLP-1 agonist tirzepatide (marketed under brand names Mounjaro® and Zepbound®) are FDA-approved prescription medications for specific uses in type 2 diabetes management and, in some cases, chronic weight management. These medications are not over-the-counter supplements and should be used only under the guidance of a licensed healthcare provider.
Compounded Drug Warning
The FDA has not approved compounded drugs and has issued safety alerts about dosing errors, product contamination, and other quality concerns. Compounded drugs are custom formulations made by pharmacies and may vary in quality, safety, and effectiveness, which can increase the risk of side effects or treatment failure. The FDA has warned against using these versions due to issues with incorrect ingredients, poor storage, or improper dosage. Always get medications from a licensed pharmacy with a valid prescription.
Individual Results May Vary
Responses to GLP-1 therapy can vary from person to person. Factors such as diet, physical activity, sleep quality, underlying medical conditions, other medications, and individual metabolism can all influence both side effects and overall results. Clinical trial outcomes may differ from real-world experiences.
Possible Side Effects
Common side effects of GLP-1 medications may include:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Stomach pain or discomfort
- Decreased appetite
- Indigestion or gas
- Redness, itching, or soreness at the injection site
Most side effects are mild to moderate and may improve as your body adjusts to treatment. If you experience severe or persistent symptoms, contact your healthcare provider promptly.
Boxed Warning (Thyroid C-Cell Tumor Risk)
GLP-1 receptor agonists, including semaglutide, carry an FDA boxed warning regarding the potential risk of thyroid C-cell tumors. Do not use if you or a family member has a history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
When to Seek Immediate Medical Attention
Contact your healthcare provider or seek emergency care if you experience:
- Severe abdominal pain that does not go away
- Signs of an allergic reaction (rash, swelling, difficulty breathing)
- Symptoms of pancreatitis (severe abdominal pain, vomiting)
- Symptoms of severe dehydration (dizziness, confusion, rapid heartbeat)
FDA Adverse Event Reporting
