Retatrutide is an new drug that has shown promise in the treatment of obesity and type 2 diabetes.
Retatrutide is a type of multi-receptor agonist that targets multiple hormonal pathways involved in blood sugar regulation, appetite control and metabolic health.
As clinical trials progress, retatrutide has garnered attention for its ability to significantly lower blood glucose levels and promote substantial weight loss.
What is Retatrutide?
Retatrutide is an investigational once-weekly injectable medication developed by Eli Lilly.
It is a triple receptor agonist meaning it activates three key hormone pathways that play a role in glucose metabolism and appetite regulation:
- Glucagon-like peptide-1 (GLP-1) receptor – involved in insulin secretion, appetite suppression, and slowing digestion.
- Glucose-dependent insulinotropic polypeptide (GIP) receptor – enhances insulin release in response to food intake and may contribute to weight loss.
- Glucagon receptor – plays a role in energy expenditure and fat metabolism.
This multi-receptor action sets retatrutide apart from existing GLP-1 receptor agonists like semaglutide (Ozempic or Wegovy) and dual agonists like tirzepatide (Mounjaro or Zepbound).
How does Retatrutide work?
Retatrutide mimics the effects of naturally occurring gut hormones to improve metabolic health.
Lowering blood sugar
Stimulating insulin release when glucose levels are high while also reducing glucagon secretion to prevent excess sugar production by the liver.
Promoting weight loss
By targeting appetite regulation centers in the brain, retatrutide reduces hunger and increases feelings of fullness, leading to lower food intake.
Boosting metabolism
The glucagon component of retatrutide helps increase energy expenditure, potentially leading to greater fat loss compared to single or dual-receptor agonists.
History of Retatrutide
Eli Lilly developed retatrutide as part of its efforts to advance next-generation therapies. The drug builds on the success of earlier treatments such as GLP-1 receptor agonists such as liraglutide and semaglutide and the dual GIP/GLP-1 agonist tirzepatide.
Preclinical studies suggested that combining GLP-1, GIP and glucagon receptor activation could yield even greater metabolic benefits than previous therapies.
Retatrutide progressed through early-phase clinical trials, showing strong potential for both glycemic control and weight reduction.
Current evidence
Retatrutide has demonstrated remarkable results in clinical trials – particularly in weight loss and blood sugar control.
In the SURMOUNT-1 Trial (a study on obesity), participants lost up to 24.2% of their body weight over 48 weeks – the most significant weight reduction seen in an anti-obesity medication to date. Higher doses of retatrutide resulted in greater weight loss.
In type 2 diabetes trials, retatrutide significantly reduced HbA1c levels, with some participants achieving near-normal glucose levels. The combination of GLP-1, GIP and glucagon receptor activation provided superior glycemic control compared to existing GLP-1-based therapies.
While results are promising, long-term safety and efficacy studies are still ongoing.
What are the side effects?
Retatrutide has shown common side effects similar to other GLP-1 receptor agonists, including:
- Nausea
- Vomiting
- Diarrohea
- Constipation
- Abdominal discomfort or bloating
Some trial participants experienced a slight increase in resting heart rate, which has also been observed with other GLP-1 receptor agonists. However, its unique action on glucagon receptors requires further research to assess long-term metabolic effects.
How Retatrutide compares
Retatrutide is shaping up to be a potentially more powerful option than existing medications.
Retatrutide’s triple action may lead to greater weight loss and potentially stronger glucose control when compared to Semaglutide.
Early results suggest retatrutide could offer even better metabolic benefits that tirzepatide, though direct comparison trials are needed.
Retatrutide works via a completely different mechanism to other weight loss drugs such as orlistat and phentermine focusing on hormonal regulation rather than just suppressing appetite or blocking fat absorption.
Potential uses
Beyond diabetes and obesity, researchers are exploring Retatrutide’s role in:
- Non-alcoholic fatty liver disease (NAFLD) where its impact on glucagon receptors suggests it may help reduce liver fat.
- Cardiovascular benefits as weight loss and improved metabolic markers could lower heart disease risk.
- Type 1 diabetes as although primarily studied in type 2 diabetes, there is potential for adjunctive use in type 1 diabetes management.
As new findings emerge, we’ll keep you updated on retatrutide’s progress:
In the meantime, if you’re considering treatment options for diabetes or weight management, consult with a healthcare professional to explore the best approach for your needs.
