Cotadutide is an investigational medication being developed to address metabolic conditions such as type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH). It is a synthetic peptide that works by mimicking the actions of two natural human hormones, glucagon-like peptide-1 (GLP-1) and glucagon, which are involved in regulating blood sugar and metabolism.
Understanding Cotadutide
What makes cotadutide distinct is its classification as a “dual agonist.” This means it activates two different types of receptors in the body: the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor (GCGR).
The dual action of cotadutide sets it apart from other medications that might only target one of these hormone pathways. By engaging both GLP-1 and glucagon receptors, cotadutide aims to provide a more comprehensive approach to managing metabolic imbalances. This combined activation is designed to influence various physiological processes related to glucose control, energy balance, and fat metabolism.
Conditions Cotadutide Targets
Cotadutide is being developed to treat complex metabolic conditions, including Type 2 Diabetes, Obesity, and Non-alcoholic Steatohepatitis (NASH). These conditions often coexist and pose significant health challenges due to their progressive nature and limited long-term treatment options. Type 2 Diabetes involves high blood sugar levels, while obesity is characterized by excessive body fat.
NASH involves the accumulation of fat in the liver, which can lead to inflammation, liver damage, and potentially more severe conditions like cirrhosis or liver failure. A dual-acting drug like cotadutide offers a promising therapeutic strategy by simultaneously addressing several underlying issues associated with these disorders, such as improving glucose regulation, promoting weight loss, and reducing liver fat.
How Cotadutide Works in the Body
Cotadutide exerts its effects by activating both GLP-1 and glucagon receptors, leading to a synergistic impact on metabolism. When cotadutide activates the GLP-1 receptor, it promotes glucose-dependent insulin secretion from the pancreas. This action helps to lower elevated blood glucose.
Activation of GLP-1 receptors also slows down gastric emptying, which helps to reduce post-meal blood sugar spikes and contributes to a feeling of fullness, leading to reduced food intake and weight loss.
Simultaneously, cotadutide’s activation of glucagon receptors influences liver function and energy expenditure. Glucagon receptor activation in the liver can reduce the production of new fats and glycogen synthesis, leading to lower lipid content and improved glucose processing within the liver. This dual action on both GLP-1 and glucagon receptors works to improve overall metabolic control, reduce liver fat, and contribute to weight management.
Clinical Trial Outcomes
Clinical trials have shown promising results for cotadutide in improving various metabolic parameters. In studies involving patients with type 2 diabetes and obesity, cotadutide led to significant reductions in HbA1c and body weight. A 54-week study demonstrated that cotadutide significantly decreased HbA1c and body weight compared to placebo at both 14 and 54 weeks.
Patients treated with cotadutide also showed improvements in liver health, with reductions in elevated liver enzymes such as AST and ALT, and positive changes in markers associated with liver fat and fibrosis. In some trials, cotadutide 300 µg resulted in greater weight loss and reductions in ALT compared to liraglutide 1.8 mg. These findings suggest cotadutide’s potential to address multiple facets of metabolic disease beyond just glucose control and weight loss, including liver health.
Safety and Administration
The safety profile of cotadutide in clinical trials indicates that it is generally well-tolerated, with common side effects primarily affecting the gastrointestinal system. These include nausea and vomiting, which are frequently reported. In one phase 2b study, nausea occurred in 35% of participants and vomiting in 17%, though these symptoms tended to decrease over time.
Cotadutide is administered as a subcutaneous injection, meaning it is given under the skin. Dosing in clinical trials has varied, with doses ranging from 50 µg to 600 µg, often with an initial titration period to allow the body to adjust. Studies have indicated that dose adjustments due to renal impairment may not be necessary, suggesting consistent tolerability across different levels of kidney function.