Retatrutide Side Effects

Common side effects

According to clinical trials so far, the most common side effects of retatrutide are related to the digestive system, such as nausea, reduced appetite, constipation, and diarrhoea.

This pattern is very similar to what we see with other GLP-1–based medications, including Mounjaro side effects, where gastrointestinal symptoms are the most frequently reported issues, particularly during the early stages of treatment while the body is adjusting.

Nausea (~40-50%)

This is the most frequently reported side effect. It usually occurs when starting treatment or increasing the dose, as the medication slows digestion and affects appetite signals. It is typically mild to moderate and improves over time.

Diarrhoea, constipation, or stomach discomfort (~10-30%)

Because retatrutide changes how quickly food moves through the gut, some people experience changes in bowel habits. These symptoms are usually temporary and settle as the body adjusts.

Vomiting (~10-20%)

Some people experience vomiting, particularly during dose increases. This is usually mild and becomes less frequent once the maintenance dose is reached.

Reduced appetite

This is actually part of how the medication helps with weight loss, but some people may notice a significant drop in hunger, especially early on.

Retatrutide effects on the heart

In clinical trials so far, the main heart-related effect seen with retatrutide is a small increase in resting heart rate. This effect appears to be dose-dependent and temporary.

What we know so far:

Small increase in resting heart rate

• On average, heart rate increased by around 5–7 beats per minute at higher doses
• This increase was most noticeable around 24 weeks of treatment
• After this point, heart rate often stabilised or began to decline as the body adjusted

What this means in real terms:

If your resting heart rate was normally 70 bpm, it might increase to around 75–77 bpm, which is still within the normal range for most people.

No significant increase in serious heart problems in trials so far

• Clinical trials did not show a clear increase in serious cardiovascular events, such as heart attacks or dangerous heart rhythm problems
• Most heart-related changes were limited to this modest heart rate increase, rather than structural or dangerous cardiac effects

This is consistent with other medications in the same class, such as GLP-1 and dual GLP-1/GIP agonists.

Why heart rate may increase slightly

This is likely due to metabolic changes caused by the medication, including:

• Increased calorie burning (via glucagon activation)
• Changes in autonomic nervous system activity
• Rapid weight loss and metabolic adaptation

These changes can cause the heart to beat slightly faster, but this is usually mild and well tolerated.

Retatrutide and hair loss

Hair loss has not been identified as a common side effect of retatrutide in clinical trials so far.

However, some people may experience temporary hair thinning during significant weight loss, regardless of the medication used. This is usually due to a condition called telogen effluvium, where rapid weight loss, reduced calorie intake, or nutritional changes cause more hairs than usual to enter the shedding phase.

This type of hair loss is typically temporary and reversible, and hair growth often returns to normal once weight stabilises and the body adjusts.

Because retatrutide is still in clinical trials, its full long-term side effect profile is still being studied. Based on similar medications like Mounjaro, hair loss is more likely related to rapid weight loss rather than a direct effect of the medication itself.

Further reading: Mounjaro Hair Loss: Causes and Prevention

There are a few serious but rare side effects that have been observed in clinical trials so far.

• Pancreatitis: Affecting ~0.3% of users
• Gallbladder disease: Affecting ~0.5-1% of users
• Elevated liver enzymes: Affecting <1-2% of users
• Increase in resting heart rate: Affecting <1% of users
• Cardiac arrhythmias: Affecting <1% of users
• Severe gastrointestinal complications: Affecting ~1-2%
• Allergic reactions: Affecting <1% of users
• Thyroid cancer: Affecting 0% of users

In the Phase 2 trials, serious side effects appear to be rare, affecting less than 2% of participants.

Retatrutide is still in Phase 3 clinical trials, so true long-term side effects (over many years) are not yet fully known. However, based on trials lasting up to 48–72 weeks, and what we know from similar GLP1 medication, here is the most accurate clinical summary:

Sustained increase in resting heart rate

• Average increase: ~5–10 beats per minute
• This persisted throughout trials (up to 48 weeks)
• Clinical significance is still being studied
• Similar effects are seen with GLP-1 and dual/triple agonists

Gallbladder disease (long-term risk)

• Risk increases with prolonged use and rapid weight loss
• Includes:
  • Gallstones
  • Gallbladder inflammation (cholecystitis)

Estimated incidence: ~0.5–1% so far

Loss of lean muscle mass

Significant weight loss includes both:

• Fat loss (majority)
• Some lean muscle loss

Estimated composition of weight lost:

• ~75–85% fat
• ~15–25% lean mass

This can affect:

• Strength
• Metabolism
• Long-term weight maintenance

Resistance training and adequate protein intake reduce this risk.

Persistent gastrointestinal symptoms (minority of patients)

Usually mild, but long-term symptoms may include:

• Nausea
• Constipation
• Reduced appetite

Unknown long-term risks (still being studied)

Because retatrutide activates three hormone pathways (GLP-1, GIP, glucagon), long-term monitoring is ongoing for:

• Cardiovascular outcomes (positive or negative)
• Pancreatitis risk
• Thyroid tumour risk (theoretical, based on drug class)
• Long-term metabolic adaptation
• Effects beyond 2–5 years

When considering retatrutide, the most important thing to keep in mind is that it is still an investigational medication.

This means it is currently only available to people participating in official clinical trials and cannot be bought at a local pharmacy yet.

Because it is a “triple-action” drug, it is more potent than current options, and doctors are paying close attention to a few specific areas:

• Step-by-step dosing: To keep your stomach happy, retatrutide must be started at a very low dose and increased slowly over several months.
• Protein and nutrition: weight loss can be so fast, and your appetite may drop significantly, so focusing on eating enough protein is vital to protect your muscle mass and keep your energy up.
• Medical history: Like other drugs in this family, it may not be suitable for people with a history of certain conditions, such as pancreatitis or specific rare types of thyroid issues like Medullary Thyroid Carcinoma.
• Contraception: Some evidence suggests that these types of medications can affect how well oral contraceptives are absorbed, so doctors often recommend using a backup method of birth control when you first start or change your dose.

Overall, retatrutide appears to be well tolerated, with most side effects being mild to moderate and like existing weight-loss medications such as Mounjaro and Wegovy. The most common side effects are digestive, such as nausea, constipation, diarrhoea, and reduced appetite, particularly during the early stages of treatment while the body adjusts.

More serious side effects have been rare in clinical trials. Gallbladder issues have been reported in around 0.5–1% of patients, and pancreatitis in approximately 0.3%. A small increase in resting heart rate, typically around 5–10 beats per minute, is common, but clinically significant heart problems have been uncommon. Importantly, there have been no confirmed cases of severe liver injury linked to retatrutide so far.

As retatrutide is still being studied, ongoing trials will provide more long-term safety data. However, based on current evidence, its safety profile is reassuring and broadly consistent with other medications in the same class, with serious complications remaining uncommon.