Retatrutide is an investigational medication showing promise in the field of metabolic health. It is currently undergoing clinical trials to evaluate its effectiveness and safety. This novel drug targets multiple pathways involved in metabolism, offering a comprehensive approach to managing certain conditions.
What Retatrutide Is
Retatrutide is a novel drug developed by Eli Lilly and Company, distinguished by its unique mechanism as a “triple agonist.” It is designed to activate three distinct hormone receptors: Glucagon-Like Peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors.
The drug’s design ensures that while all three receptors are engaged, it exhibits particular potency at the GIP receptor. Activating the GIP receptor facilitates insulin secretion in a glucose-dependent manner and influences lipid metabolism, which can help reduce fat deposition and improve overall energy balance. This stronger effect at the GIP receptor is considered a differentiating factor from other incretin-based therapies.
The activation of GLP-1 receptors by retatrutide enhances insulin secretion, helping to control blood glucose levels and promoting a sense of fullness. Simultaneously, its interaction with glucagon receptors, although moderate, aids in increasing energy expenditure and fat breakdown. This combined action across GLP-1, GIP, and glucagon receptors results in a synergistic effect that aims to reduce appetite, enhance insulin sensitivity, and promote energy expenditure.
How Retatrutide Helps
Retatrutide is being investigated for its therapeutic effects primarily in the management of obesity and type 2 diabetes. Clinical trials have shown promising results in both areas.
In studies involving individuals with obesity, retatrutide has led to significant body weight reductions. For instance, participants receiving the highest dose of retatrutide in a phase 2 trial experienced an average weight loss of over 24% of their starting body weight within 48 weeks. This level of weight reduction surpasses outcomes observed with some other weight loss medications.
For people with type 2 diabetes, retatrutide has demonstrated clinically meaningful improvements in blood sugar control. Participants in a phase 2 trial showed reductions in their HbA1c levels, a key measure of long-term blood sugar control, with higher doses leading to more substantial decreases. The drug also contributed to weight loss in individuals with type 2 diabetes, with average reductions of around 16% over 36 weeks at higher doses.
Beyond weight and blood sugar, retatrutide has also shown benefits in reducing liver fat accumulation, with a high percentage of participants achieving normalization of liver fat in studies involving individuals with non-alcoholic fatty liver disease (NAFLD).
Is There an Oral Retatrutide?
Retatrutide is currently administered as a once-weekly injectable medication. This is a common method for drugs that are proteins or peptides. Such molecules are generally not well-absorbed orally due to their instability in the gastrointestinal (GI) tract and limited ability to cross the intestinal lining.
The digestive system’s harsh environment, including varying pH levels from acidic in the stomach to alkaline in the small intestine, and the presence of numerous enzymes like pepsin, can break down proteins and peptides. This degradation prevents them from reaching the bloodstream intact and in sufficient quantities to be effective.
While there is a strong demand for oral formulations of protein and peptide-based drugs due to patient preference and compliance, developing them presents significant challenges. Researchers are exploring various technologies, such as encapsulation in nanoparticles or using permeation enhancers, to overcome these GI barriers. However, as of now, retatrutide remains an injectable medication, and there is no publicly available information indicating advanced research or development of an oral formulation.
Important Considerations for Retatrutide
Retatrutide is still an investigational drug and has not yet received approval for general use. Data from phase 1 and phase 2 trials indicate that the medication is generally well-tolerated.
Common side effects reported in studies are primarily gastrointestinal. These include nausea, diarrhea, vomiting, and constipation. These symptoms are often mild to moderate and tend to decrease as the body adjusts to the medication, particularly with proper dosing adjustments. The incidence of gastrointestinal adverse reactions can be dose-dependent, with higher doses sometimes leading to a greater occurrence of these issues.
Less common side effects have also been observed, such as a slight increase in resting heart rate, particularly during the initial weeks of treatment, though heart rates typically normalize over time. Concerns regarding liver enzymes and the potential for gallstones have also been noted, especially with rapid weight loss. Regular monitoring of these parameters is part of the clinical trial process.