Retatrutide

Retatrutide is an investigational, once-weekly injectable drug that is being reviewed for the management of obesity and type 2 diabetes. It belongs to a class known as triple agonists, meaning it helps activate the receptors for three hormones: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1), and glucagon. By acting on these targets, retatrutide may help reduce appetite and support healthier blood sugar levels. To date in 2026, no regulatory body has approved it, and the only way to access it is through participation in a clinical trial.

Directions

At this time, retatrutide is intended for use in an authorized clinical trial or exactly as directed by a healthcare provider. In phase 2 studies, it was given as a weekly under-the-skin injection into the abdomen, thigh, or upper arm, and on the same day each week. Dosing generally starts at 2 mg per week and is increased gradually over several weeks to 4 mg, 8 mg, or 12 mg.

If you forget a dose, follow your healthcare provider’s directions and avoid taking two doses at the same time. The medication is meant to complement a calorie-reduced diet and a more active lifestyle.

Ingredients

The active ingredient in this medication is retatrutide.

Cautions

Before you start this medication, consider discussing the following with a healthcare provider:

• Any health conditions you have
• Any allergies you have
• A complete list of the medications you take

Use retatrutide only under a clinician’s supervision, since data on its long-term safety is still incomplete.

Trials showed that higher retatrutide doses increased heart rate, with the effect peaking around week 24. Your healthcare provider may keep an eye on your heart rate and blood pressure, especially if you have heart disease.

Gastrointestinal effects such as nausea, vomiting, and diarrhea occur frequently, mainly at the start of treatment or after a dose increase. Severe or continuing vomiting and diarrhea may lead to dehydration and possible kidney problems.

For people with type 2 diabetes who also use insulin or insulin-stimulating medications, the risk of low blood sugar, also called hypoglycemia, can increase, and the dose of those medicines may need to be lowered.

Medications in the GLP-1 receptor agonist category have been tied to pancreatitis and gallbladder complications. Seek medical care for intense abdominal pain, fever, or a yellow tint to the skin or eyes.

Because retatrutide delays stomach emptying, it may alter the absorption of food and other medicines taken by mouth.

Contraindications

Based on what is known about its drug class and the enrollment criteria of clinical trials, retatrutide should be avoided in the following cases:

• A previous serious allergic, or hypersensitivity, reaction to retatrutide or any ingredient it contains.
• A personal or family background of medullary thyroid carcinoma, or MTC, or Multiple Endocrine Neoplasia syndrome type 2, or MEN 2.
• During pregnancy or while breastfeeding, because retatrutide has not been tested in these groups.

Side Effects

The side effects most commonly linked to retatrutide in clinical trials involved the gastrointestinal tract. These are usually mild to moderate and typically appear when treatment starts or the dose is increased. They can include:

• Nausea
• Diarrhea
• Vomiting
• Constipation
• Loss of appetite
• Elevated heart rate

As retatrutide is still being investigated, not all serious side effects are known. Get medical help if you develop signs of a serious allergic reaction, such as trouble breathing, a severe rash, or swelling of the face, lips, tongue, or throat. Seek emergency care for severe or persistent abdominal pain, especially pain that moves toward the back, as it could mean pancreatitis. Notify your healthcare provider about heavy vomiting, diarrhea, or warning signs of low blood sugar like shakiness, sweating, confusion, or a pounding heartbeat. Be sure to mention any new neck lump or swelling, hoarseness, or difficulty swallowing as well.

References

1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526.

2. Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. Lancet. 2023;402(10401):529-544.

Medically Reviewed by Dr. Gerardo Sison

Dr. Sison graduated with honors from the University of Florida and has experience in community pharmacy, hospitals, clinics, and medication therapy management services. All information shared here at CanPharm has been medically reviewed and fact-checked for accuracy based on current guidelines, professional consensus, and the latest available research.