Mazdutide 10mg vial

                                            NOT FOR HUMAN CONSUMPTION

Mazdutide is an investigational, once-weekly injectable peptide developed collaboratively by Innovent Biologics and Eli Lilly. It functions as a dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). This dual mechanism aims to synergistically enhance glycemic control and promote weight loss, positioning mazdutide as a promising therapeutic candidate for obesity and type 2 diabetes mellitus (T2DM).

2. Mechanism of Action

Mazdutide's dual agonism of GLP-1R and GCGR facilitates multiple metabolic benefits:

• GLP-1R Activation: Enhances glucose-dependent insulin secretion, suppresses glucagon release, delays gastric emptying, and promotes satiety.

• GCGR Activation: Increases energy expenditure and promotes lipolysis, contributing to weight reduction.

By concurrently targeting these receptors, mazdutide aims to achieve superior metabolic outcomes compared to agents that activate GLP-1R alone.

3. Clinical Efficacy

3.1. Phase 2 Trial in Overweight and Obese Adults

A randomized, double-blind, placebo-controlled Phase 2 trial evaluated mazdutide's efficacy over 24 weeks in Chinese adults with overweight or obesity. 

• Participants: 248 individuals randomized to receive mazdutide (3 mg, 4.5 mg, or 6 mg) or placebo.

• Results:

  • Mazdutide 3 mg: Mean weight reduction of 6.7%.

  • Mazdutide 4.5 mg: Mean weight reduction of 10.4%.

  • Mazdutide 6 mg: Mean weight reduction of 11.3%.

  • Placebo: Mean weight change of +1.0%.

All mazdutide doses were well tolerated, with gastrointestinal symptoms (e.g., nausea, diarrhea) being the most common adverse events.

3.2. Phase 3 GLORY-1 Study

The GLORY-1 Phase 3 trial assessed mazdutide's efficacy in weight management among adults with obesity or overweight.

• Findings:

  • Significant weight loss compared to placebo.

  • Reduction in waist circumference and improvement in cardiometabolic risk factors.

3.3. Phase 3 DREAMS-2 Study

In the DREAMS-2 Phase 3 trial, mazdutide was compared to dulaglutide in Chinese patients with T2DM. 

• Outcomes:

  • Mazdutide demonstrated superior glycemic control and greater weight reduction compared to dulaglutide.

4. Safety and Tolerability

Across clinical trials, mazdutide has exhibited a favorable safety profile:

• Common Adverse Events: Gastrointestinal symptoms such as nausea and diarrhea, generally mild to moderate in severity.

• Serious Adverse Events: No significant increase in serious adverse events compared to placebo.

• Cardiovascular Safety: No notable adverse effects on heart rate or blood pressure.

5. Pharmacokinetics

• Administration: Subcutaneous injection once weekly.

• Half-life: Extended half-life supporting weekly dosing.

• Metabolism: Primarily degraded by proteolytic enzymes; minimal renal excretion.

6. Regulatory Status and Future Directions

Mazdutide is currently undergoing Phase 3 clinical trials for obesity and T2DM. Pending successful outcomes, regulatory submissions are anticipated in the near future. Its dual receptor activity positions it as a potential alternative to existing GLP-1R agonists, with the added benefit of enhanced weight loss through increased energy expenditure.

7. Conclusion

Mazdutide represents a novel therapeutic approach targeting both GLP-1 and glucagon receptors to address obesity and T2DM. Clinical trials have demonstrated its efficacy in weight reduction and glycemic control, with a tolerable safety profile. Ongoing Phase 3 studies will further elucidate its potential role in the management of metabolic disorders.

References:

1. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) in Chinese adults with overweight or obesity: a randomised, double-blind, placebo-controlled, phase 2 trial. Nature Communications.

2. Innovent Presents the Results of the First Phase 3 Study of Mazdutide for Weight Management at the ADA's 84th Scientific Sessions. PR Newswire. 

3. Innovent's Phase 3 Clinical Trial DREAMS-2 of Mazdutide in Chinese Patients with Type 2 Diabetes Were Orally Presented at EASD 2024. PR Newswire.