Retatrutide Side Effects: What Clinical Trials Reveal About Risks and Weight Loss

Key Takeaways

Weight loss medications are more popular than ever, with several highly effective options already on the market. Retatrutide is one potential weight loss treatment still being developed by researchers.

Retatrutide works differently from medications being prescribed for weight loss right now. Semaglutide (Ozempic, Rybelsus, Wegovy) works by mimicking one hunger-regulating hormone (GLP-1). Tirzepatide (Mounjaro, Zepbound) mimics two (GLP-1 and GIP).

Retatrutide is the first drug to mimic three different metabolic hormones (GLP-1, GIP, and glucagon). This triple-hormone mechanism is a main reason why retatrutide causes such large weight loss: it affects your appetite, blood sugar, and energy use.

The full safety profile of retatrutide is still being explored, including its long-term effects.

What is retatrutide and what is it being studied for?

Retatrutide is an experimental drug being studied for its use as a weight loss medication, as well as a treatment for several conditions related to metabolic health and obesity:

• Type 2 diabetes
• Obstructive sleep apnea (OSA)
• MASLD (Metabolic dysfunction-associated steatotic liver disease)—a fatty liver disease
• Knee osteoarthritis
• Cardiovascular and chronic kidney disease

Because retatrutide is still in development, it is not approved for commercial sale or prescription by healthcare providers.

What are the most common side effects of retatrutide?

Because retatrutide acts on GLP‑1 and related pathways, its most common side effects are gastrointestinal (GI). Clinical studies show that these GI symptoms are mostly mild to moderate. They are most common during early dose increases and with faster or larger dose increases. Recent Phase 3 clinical trials looked at patients taking the highest dose (12 mg) of retatrutide. The most commonly reported side effects included:

• Nausea: Up to 43% of patients
• Vomiting: Up to 34% of patients
• Diarrhea: Up to 26% of patients
• Constipation: Up to 25% of patients
• Reduced appetite was reported in Phase 2 trials

These GI side effects are similar to those of other GLP-1-based medications. They were significantly reduced by starting with a lower dose of retatrutide and increasing the dosage gradually.

During Phase 3 trials, researchers also noted another mild-to-moderate side effect called dysesthesia—a tingling, burning, or altered sensation in the skin. Depending on the dose, roughly 9% to 20% of patients reported experiencing this.

Researchers believe this skin sensitivity is linked to how retatrutide acts on glucagon receptors. This side effect mostly resolved on its own as treatment continued, and patients rarely had to stop taking the medication because of it.

Rare or potentially serious side effects of retatrutide

Because retatrutide is still in the clinical trial phase, researchers are actively collecting data to understand its long-term impact on the body. Possible rare but serious side effects of the drug seem to include severe gastrointestinal complications and cardiovascular changes.

During a Phase 2 trial for obesity, up to 6% of patients taking retatrutide experienced serious adverse events (side effects that were life-threatening or required hospitalization). In comparison, 4% of patients experienced a serious adverse event while taking a placebo (a drug with no medical effect).

Importantly, some patients experienced an elevated resting heart rate. This was most noticeable around the 6-month mark (24 weeks) but generally declined as treatment continued.

Before the drug can be approved for the public, the FDA must assess all completed Phase 3 clinical trial data on the safety of retatrutide.

Eli Lilly (who is also the manufacturer of the weight loss drug Zepbound) is expected to finish these final Phase 3 trials throughout 2026. While they have not officially announced any dates, the drug could be submitted for FDA approval as early as late 2026 or early 2027.

Who should be cautious about using retatrutide?

Only a qualified healthcare professional can assess and determine whether a prescription medication is safe for you. Because the FDA has not yet released a final safety profile for retatrutide, it should not be used outside of an approved clinical trial setting, and there is no definitive list of who should avoid it.

However, researchers are closely monitoring safety signals in ongoing trials. Based on early studies and the known side effects of approved GLP-1-acting medications, extra caution may be advised for the following patient groups:

• Serious GI conditions: One study on humans and mice showed that retatrutide significantly slows down how fast your stomach empties. While this is one of the benefits of the medication, it may actually cause people with severe gastrointestinal conditions to have severe side effects.
• Pancreatitis: Large clinical trials have not shown a solid link between GLP-1 medications and pancreatitis. However, the FDA still lists pancreatitis as a rare but serious side effect of existing GLP-1 and GIP drugs.
• Complex cardiovascular conditions: Phase 2 clinical trials show retatrutide can cause changes in blood pressure, occasional irregular heartbeats (arrhythmias), and increases in resting heart rate (especially at higher doses).
• Chronic kidney disease: FDA labels for GLP-1 drugs recommend closely monitoring kidney function in patients with a history of kidney conditions.

How retatrutide may support weight loss

Retatrutide can cause substantial weight loss. Recent clinical trials show that participants taking the highest dose of retatrutide (12 mg) lost an average of 28% of their body weight (about 70 pounds) over 80 weeks.

In a study extension, patients with a baseline BMI of 35 or higher who stayed on this maximum dose for 104 weeks lost an average of 30% of their body weight (85 pounds).

This level is similar to the results from patients who have bariatric surgery. Some patients actually dropped out of Phase 3 trials because they reported losing too much weight.

Retatrutide causes weight loss by:

• Lowering your appetite and hunger signals, so your calorie intake is lower
• Slowing your stomach emptying, which keeps you feeling fuller for longer after meals
• Keeping your blood sugar stable and improving how your body releases and responds to insulin

Frequently asked questions

How long do retatrutide side effects last?

Retatrutide side effects are usually worse early on and improve over several weeks as your body adjusts.

• Digestive Issues: Nausea and diarrhea typically peak during the first period where doses are increased. They then decline as treatment continues.
• Heart rate increases: This side effect generally peaks temporarily around week 24 before gradually declining.

Exact individual symptom timelines are not yet known until final Phase 3 clinical trials studies are complete.

How fast do you lose weight on retatrutide?

Clinical trials show that people on retatrutide usually start losing weight in the first 4 to 8 weeks. This weight loss continues through at least 9 to 12 months on treatment without a clear plateau. Weight loss tends to be slower and smaller in people with type 2 diabetes than in those without diabetes, and results are different from person to person.

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