Cotadutide

Human clinical Weight Loss & Metabolism 2 sources

Cotadutide is an investigational dual agonist of the GLP-1 and glucagon receptors. Research indicates it improves glycemic control, promotes weight loss, and shows significant potential for improving liver health, particularly in conditions like non-alcoholic steatohepatitis (NASH).

01Dosing reference

Amount

100-300 mcg/day

Frequency

Once daily

Cycle

Continuous daily use in clinical trials (e.g., 12-54 weeks)

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

Dual Receptor Activation

Cotadutide binds to and activates both the glucagon-like peptide-1 (GLP-1) and glucagon receptors.

Metabolic and Hepatic Regulation

It increases insulin secretion and delays gastric emptying via GLP-1, while increasing energy expenditure and lipid metabolism via glucagon.

Clinical Outcomes

This dual action leads to improved blood glucose levels, significant weight loss, and reduced liver fat and inflammation.

03Human evidence

Significant reductions in HbA1c and body weight compared to placebo in patients with type 2 diabetes.

Phase 2b clinical trials involving patients with type 2 diabetes and overweight/obesity, demonstrating dose-dependent efficacy.

Reductions in liver fat content and improvements in liver enzymes (AST/ALT).

Phase 2a trials in patients with non-alcoholic steatohepatitis (NASH) and overweight/obesity.

04Preclinical evidence

Greater weight loss and liver fat reduction compared to GLP-1 monotherapy.

Animal models of diet-induced obesity, highlighting the added benefit of glucagon receptor agonism.

Reduced hepatic inflammation and fibrosis.

Rodent models of NASH, suggesting potential disease-modifying effects in the liver.

05What is known vs. unknown

Reasonably established

Acts as a dual agonist targeting both GLP-1 and glucagon receptors.
Demonstrates efficacy in reducing HbA1c and body weight in human trials.
Shows significant promise for reducing liver fat and improving NASH markers.
May offer renal benefits, as seen in trials involving patients with chronic kidney disease.

Unknowns & limits

Long-term cardiovascular safety and outcomes are not yet fully established.
Optimal dosing to balance efficacy and gastrointestinal tolerability needs further refinement.
Not yet FDA-approved for any indication.

06Safety & regulatory context

Regulatory statusCotadutide is currently an investigational drug and is not FDA-approved. In clinical trials, the most common adverse events were gastrointestinal in nature, such as nausea, vomiting, and diarrhea, which are typical for incretin-based therapies. The safety profile appears similar to other GLP-1 receptor agonists, though the addition of glucagon agonism requires careful monitoring of heart rate and glycemic balance.

07Compared with Semaglutide

Cotadutide vs. Semaglutide

Key difference

Cotadutide is a dual GLP-1/glucagon receptor agonist, whereas Semaglutide is a selective GLP-1 receptor agonist.

When researchers discuss each

Semaglutide is discussed as a standard highly effective GLP-1 agonist for diabetes and obesity, while Cotadutide is discussed when exploring the added metabolic and hepatic benefits of glucagon receptor co-activation, particularly for NASH.

08Glossary

GLP-1 Receptor Agonist

A class of drugs that mimic the incretin hormone GLP-1 to increase insulin secretion and lower blood sugar.

Glucagon

A hormone that typically raises blood sugar but also increases energy expenditure and lipid metabolism.

NASH

Non-alcoholic steatohepatitis, a severe form of fatty liver disease characterized by inflammation and liver damage.

09Knowledge check

Q1What two receptors does Cotadutide target?

Q2Which liver condition has Cotadutide shown significant promise in treating during Phase 2 trials?

Q3Which of the following is an explicitly stated limitation of the current Cotadutide evidence in the dossier?

Q4According to the dossier, researchers most often discuss Cotadutide instead of Semaglutide when exploring which context?

Q5Which safety or monitoring concern is specifically highlighted in the dossier because of Cotadutide’s glucagon agonism?

10Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.