Retatrutide Side Effects: What the Clinical Trials Have Found So Far

Retatrutide is still an experimental drug. Regulators have not approved it for weight loss in the UK. However, we now know more about retatrutide side effects than we did before the peer-reviewed Phase 2 study from the New England Journal of Medicine in 2023. Since then, the manufacturer, Eli Lilly and Company, has reported topline results from the Phase 3 TRIUMPH trials. [1-5]

Evidence on side effects is becoming clearer. Gastrointestinal effects remain the primary tolerability issue, while Phase 3 results have provided more insight into dysesthesia, which involves abnormal sensations in the skin. However, there's still no real-world safety evidence on long-term side effects, as with other licensed weight loss medications such as Mounjaro and Wegovy.

Key Takeaways

• Retatrutide is not authorised for use in the UK.
• The most common retatrutide side effects are gastrointestinal, including nausea, diarrhoea, vomiting and constipation.
• Gastrointestinal symptoms occur more often with higher doses and during dose escalation.
• Phase 3 trials have strengthened the safety signal for dysesthesia, which can cause tingling, burning or unusual skin sensitivity.
• Retatrutide can increase heart rate, and researchers continue to study its cardiovascular effects.
• Retatrutide has no extensive post-marketing safety record because it hasn't been approved for use.
• Mounjaro and Wegovy have some similar GLP-1-related side effects to retatrutide. However, direct comparisons between separate clinical trials can't establish which drug has better side effects.

Retatrutide Is Not Available in the UK

If you're looking into retatrutide to compare with Mounjaro and Wegovy, or some product you've seen online, put its safety evidence in context.

Retatrutide is still undergoing clinical development. The Medicines and Healthcare products Regulatory Agency (MHRA) hasn't approved it for use in the UK. Thus, any product on the market that contains retatrutide outside of an authorised clinical trial is probably illegal and potentially harmful. [6]

Eli Lilly is the manufacturer of this experimental drug and uses it in their retatrutide clinical trials. Usually, the doses are prescribed, and there’s monitoring of the participants in the clinical trials. The company warns that products marketed as having retatrutide that aren’t part of clinical trials may contain contaminants, unidentified ingredients, or incorrect quantities. [7]

This means that the known side effects of retatrutide are from the controlled clinical trials conducted by Eli Lilly. So, it’s not possible to predict what may happen after injecting an unlicensed product from the grey market.

The same logic applies to other weight loss injections. FDA-approved GLP-1 drugs have undergone testing and approval processes. Therefore, buying an unapproved drug online circumvents those safeguards.

What Retatrutide Is and Why GLP-1 Side Effects Occur

GLP-1, GIP, and Glucagon Receptors

Retatrutide is an investigational triple agonist that activates GLP-1, GIP, and glucagon receptors. In contrast, the active component in Wegovy, semaglutide, acts on GLP-1 receptors, whereas the active component in Mounjaro, tirzepatide, acts on GIP receptors along with GLP-1 receptors.

These overlapping pathways explain why retatrutide side effects resemble those of other incretin-based weight-loss medications. The activity of GLP-1 may help inhibit appetite and decrease the rate of gastric emptying. GIP also affects insulin production and blood glucose control. Together, these effects can support weight loss and improve metabolic markers, but they can also cause nausea, vomiting, and other gastrointestinal symptoms.

Retatrutide also has glucagon receptor activity. Researchers are still investigating the impact of this third pathway on energy intake, body weight, blood sugar, and other metabolic effects. They haven't established any association between glucagon activity and specific adverse effects, such as dysesthesia. For more insight, read our guides on what retatrutide is and retatrutide vs Mounjaro.

How Much Weight Has Retatrutide Reduced in Clinical Trials?

Retatrutide received considerable interest in the Phase 3 TRIUMPH-1 study. By the end of the trial (80 weeks), the weight loss efficacy estimands for the 4 mg, 9 mg, and 12 mg groups were 19.0%, 25.9%, and 28.3%, respectively, compared with 2.2% in the placebo group. [2]

Please note that these figures can't estimate the amount of weight any individual will lose, and abrupt or significant weight loss can present other health concerns.

Common Retatrutide Side Effects in Clinical Trials

Nausea, Vomiting, Diarrhoea, and Constipation

The most common adverse events are gastrointestinal. The results of both Phase 2 and Phase 3 trials have indicated nausea, vomiting, diarrhoea, and constipation as the most common retatrutide adverse effects.

The peer-reviewed Phase 2 study showed that gastrointestinal (GI) side effects were more prevalent with retatrutide than with placebo. These were mostly mild to moderate, mainly occurring when the dose was increased, and became more frequent at higher doses. The incidence of these side effects was lower when participants started at a lower dose. [1]

The pattern is similar in Phase 3, but the rates vary in different trial populations. The incidence of nausea was 28.6% in the TRIUMPH-1 group 4 mg, 38.4% in group 9 mg, and 42.4% in group 12 mg. Vomiting occurred in 10.6%, 22.8%, and 25.3% of those groups. Diarrhoea affected 25.2%, 34.1%, and 32.0%, while constipation occurred in 23.8%, 25.9%, and 26.1%. [2]

TRIUMPH-4, which involved adults with obesity or overweight and knee osteoarthritis, reported nausea in 43.2% of 12 mg subjects, vomiting in 20.9%, diarrhoea in 33.1%, and constipation in 25.0%. [3] Such data explain why it’s misleading to state that nausea always affects a fixed percentage of retatrutide users. This rate can vary depending on the dose of retatrutide used, study design, and patients.

Side Effects by Retatrutide Dosage

These categories reflect the overall pattern, not the risk estimate, because they combine data from incompatible clinical trials.

Dose Escalation and Tolerability

Dose escalation means that researchers gradually increase a participant's assigned dose instead of starting immediately at the target or maintenance dose.

The distinction is important because many of the gastrointestinal side effects are the result of the rise in dose. Gastrointestinal adverse events were reduced to some degree in the lower starting-dose group in Phase 2 [1]. In addition, the Phase 3 programme has involved increasing doses, instead of starting participants on higher doses immediately.

This information describes the trial design. This isn’t a retatrutide UK dosage guide. Never use trial schedules to self-administer an unlicensed product.

Other Retatrutide Side Effects Researchers Are Monitoring

Dysesthesia and Changes in Skin Sensitivity

Dysesthesias refer to an abnormal, unpleasant sensation in the skin. It causes a tingling, burning, heightened sensitivity, or an unusual sensation when you touch your skin. This is one of the more notable retatrutide side effects in Phase 3 trials.

Retatrutide trial results have reported dysesthesia, which can cause tingling, burning, or unusual skin sensitivity. In the Phase 3 TRIUMPH-4 trial, 8.8% of the 9 mg group and 20.9% of participants receiving 12 mg reported dysesthesia, compared with 0.7% in the placebo group. However, these events were generally mild and did not lead to treatment discontinuation. [3]

The rate has varied considerably between retatrutide trial results. In the Phase 3 TRIUMPH-1 trial, dysesthesia occurred in 5.1% of participants on 4 mg, 12.3% on 9 mg, and 12.5% on 12 mg, compared with 0.9% in the placebo group. By comparison, diabetes-specific studies, such as TRANSCEND-T2D-1, showed lower rates, with dysesthesia affecting 4.5% (4 mg), 2.3% (9 mg), and 4.4% (12 mg).

Heart Rate and Heart Rhythm Changes

The trials also established that retatrutide can cause dose-dependent effects on heart rate. The Phase 2 study showed a dose-dependent increase in heart rate that rose until around week 24, then declined. In the 12 mg group, 24-hour monitoring showed an increase of approximately 6.7 bpm at week 36. [1] These findings do not, by themselves, establish long-term cardiovascular harm.

In the same study, 6% of the study participants experienced adverse events related to cardiac arrhythmia, with varying rates across the different doses, up to 11% in the 12 mg dose. These were mostly mild to moderate. The trial also reported two significant adverse cardiovascular events among the participants, so claims that "no serious cardiac events" occurred are not accurate. [1]

Phase 3 has since added cardiovascular evidence. TRIUMPH-3 studied people with class II or III obesity and established cardiovascular disease, with or without type 2 diabetes. The company-reported topline findings included cardiovascular-event data, but they still need longer follow-up and dedicated cardiovascular outcomes evidence before drawing firm conclusions about heart attacks, strokes, or cardiovascular death. [4]

But it's not wise to take individual studies and assume that retatrutide's heart rate effect is definitely greater than Mounjaro or Wegovy's. No direct trial has made that comparison.

Less Common Adverse Events

The Phase 2 trial also documented injection site reactions, hypersensitivity events, biliary disorders, and increases in pancreatic enzymes. One acute pancreatitis event was recorded. Mean ALT and AST values didn't differ significantly from baseline or change at week 48. However, ALT liver enzymes increased above three times the upper limit of normal in 1% of participants receiving retatrutide. [1] The Phase 2 study found no medullary thyroid cancers or C-cell hyperplasia.

Is Retatrutide Safe? What We Still Don't Know

The question of safety requires a distinction between tolerability during the trial phase and approval for the drug by the regulatory authorities. So, what do we know?

Safety data from Phase 2 and Phase 3 studies are now available. Side effects are mainly gastrointestinal intolerance. Tolerability depends on dose and dose escalation, and the Phase 3 results provide much more information about dysesthesia as another possible side effect.

What remains incomplete? The 2023 Phase 2 obesity study went through peer review and appeared in the New England Journal of Medicine. Some of the newest Phase 3 information comes from Eli Lilly's company-reported topline results. These releases provide useful data, but they're not as detailed as complete peer-reviewed publications.

In July 2026, Lilly said results from TRIUMPH-2 and TRIUMPH-3 gave it a Phase 3 clinical-data package to support planned global regulatory submissions. [4] What doesn't exist yet is an extensive safety record. There have been no trials of retatrutide in the real world, so no long-term data from routine prescribing is available.

Why Buying Retatrutide Online Is a Serious Risk

Retatrutide adverse effects come from clinical trials. Therefore, an online vial comes with another set of unknowns. You can't be sure what's inside. Unregulated products may contain the wrong dose, contaminants, impurities, or a different ingredient. Both Lilly and the MHRA have warned us about this issue. [6,7]

Also, there's no appropriate clinical supervision. Weight-loss medications must be evaluated because medical history, other medications, and personal risk factors can affect whether they’re appropriate.

The MHRA continues to warn people against unregulated weight loss medications sold online and through social media. It states specifically that retatrutide hasn't been authorised in the UK and that anyone selling it here is doing so illegally. [6]

What Is Available in the UK Instead

If you want to lose weight with medical support, the UK offers licensed options. For instance, the ingredient in Mounjaro, tirzepatide, is a dual GIP and GLP-1 agonist. It targets two of the three receptors that retatrutide targets. Gastrointestinal side effects, including nausea, diarrhoea and constipation, are also common, as with retatrutide, especially as the dose increases. During the SURMOUNT-1 obesity study, 4.3% to 7.1% of patients (by dose) discontinued treatment due to adverse events. [8]

Semaglutide in Wegovy acts on GLP-1. It has a longer regulatory and post-marketing history than retatrutide. Wegovy also has cardiovascular outcomes evidence. The SELECT trial found a 20% reduction in major adverse cardiovascular events compared with placebo among people with established cardiovascular disease and overweight or obesity. [9]

Oral semaglutide is now authorised in the UK as an option for weight management. At Curely, we currently list the Wegovy pill alongside other treatment options for weight management. Read our guide on which GLP-1 is best for weight loss, which compares licensed options in more detail.

Getting Licensed Weight Loss Treatment with Curely

At Curely, we're a UK online pharmacy registered with the General Pharmaceutical Council under registration number 9012401.

If you're looking for weight loss support, you'll simply complete an online health questionnaire covering your medical history and treatment needs. A UK-registered pharmacist reviews your information and, if prescription treatment is suitable, guides you through the available options.

Please note that we only prescribe licensed weight management treatments, not experimental retatrutide. We source medication from regulated UK suppliers and deliver it in discreet packaging after approval.

The right weight loss medication depends on your health, eligibility and treatment goals. A clinical assessment lets the prescriber consider those factors, rather than treating every GLP-1 medicine or weight-loss injection as interchangeable. Start your weight-loss consultation today.

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Frequently Asked Questions

How Long Do Retatrutide Gastrointestinal Side Effects Last?

There's no fixed duration. In Phase 2, gastrointestinal side effects such as nausea, vomiting, and diarrhoea occurred mainly during dose increases and were often temporary. [1] Symptoms may ease after several weeks or with longer treatment, but this varies by individual.

Does Retatrutide Cause Hair Loss?

Current clinical evidence hasn't established hair loss as a characteristic retatrutide adverse effect. However, substantial or rapid weight loss can sometimes cause temporary hair shedding. If you experience persistent or unexplained hair loss, speak to a healthcare professional.

Does a Higher Retatrutide Dosage Mean More Side Effects?

For several side effects, particularly nausea and vomiting, trials show a dose-related pattern. Higher doses and dose increases can make gastrointestinal symptoms more common. However, rates vary between studies, so don't treat trial dosing schedules as instructions for taking unlicensed retatrutide.

Is Retatrutide Safer Than Mounjaro Or Wegovy?

There's no reliable head-to-head evidence to allow a simple safety ranking when comparing retatrutide with Mounjaro or Wegovy. All three can cause gastrointestinal side effects because they involve GLP-1 activity. However, Mounjaro and Wegovy are licensed medicines with regulatory and real-world safety data, while retatrutide is still undergoing clinical trials.

Is Retatrutide Safe?

Clinical trials suggest that most participants tolerate retatrutide, with most side effects involving the digestive system and generally being mild to moderate. Researchers have also observed changes in resting heart rate and continue to assess cardiovascular safety. Retatrutide remains investigational, so regulators have NOT approved it for routine prescribing.

When Should I Get Medical Help for Side Effects?

Speak to a healthcare professional if side effects persist, worsen, or cause problems such as repeated vomiting or dehydration. Severe or persistent abdominal pain, chest symptoms, serious breathing difficulties, or signs of a severe allergic reaction require urgent medical attention. Call 999 in an emergency.

Conclusion

The findings from Phase 2 and Phase 3 give us a clearer picture of retatrutide's safety, but important questions remain. Gastrointestinal side effects, particularly nausea, vomiting, diarrhoea and constipation, remain the main tolerability issue, especially at higher doses and during dose increases.

Phase 3 trials have also provided more information about dysesthesia. TRIUMPH-4 reported dysesthesia in 20.9% of participants receiving 12 mg, although other trials have reported lower rates. Researchers continue to study changes in heart rate and longer-term cardiovascular outcomes.

Retatrutide remains investigational, so it lacks long-term, real-world safety evidence that comes with regulatory approval and routine use. If you're looking for weight-loss support now, Curely prescribes regulated weight management treatments to eligible UK patients after a clinical assessment.

Reference List

• Jastreboff AM, et al. “Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial.” New England Journal of Medicine. 2023;389:514–526.
• Eli Lilly and Company. TRIUMPH-1 Phase 3 topline results. May 2026.
• Eli Lilly and Company. TRIUMPH-4 Phase 3 topline results. December 2025.
• Eli Lilly and Company. TRIUMPH-2 and TRIUMPH-3 Phase 3 topline results. July 2026.
• Eli Lilly and Company. Phase 3 retatrutide clinical programme and reported trial results, 2025–2026.
• Medicines and Healthcare products Regulatory Agency. UK guidance and warnings on unauthorised retatrutide and illegal weight loss medicines.
• Eli Lilly and Company. Patient information concerning investigational retatrutide and products sold outside Lilly clinical trials.
• Jastreboff AM, et al. “Tirzepatide Once Weekly for the Treatment of Obesity.” New England Journal of Medicine. 2022;387:205–216.
• Medicines and Healthcare products Regulatory Agency. Semaglutide approval information for reducing serious cardiovascular events in adults with overweight or obesity and established cardiovascular disease.