Mazdutide dosage protocol

What Mazdutide is

Mazdutide (also known as IBI362 or LY3305677) is a pharmaceutical compound classified as a novel glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist (PMID 36247927, PMID 40421736, PMID 41054801). It is an incretin-based dual agonist pharmacotherapy (PMID 40421736).

It is being developed by Eli Lilly and Company along with Innovent Biologics (PMID 41028652). Mazdutide received its first approval in China in June 2025 for long-term body weight management in adults with obesity or overweight, when used with diet control and increased physical activity (PMID 41028652). Subsequently, in September 2025, it was also approved in China for glycemic control in adults with type 2 diabetes (PMID 41028652).

How it is thought to work

Mazdutide functions as a dual agonist for both the glucagon receptor (GcgR) and the glucagon-like peptide-1 receptor (GLP-1R) (PMID 41028652). It is considered a multi-agonist therapy (PMID 42208956).

As a next-generation GLP-1-based therapeutic, mazdutide engages not only GLP-1 receptors but also receptors for other gastro-entero-pancreatic hormones, such as glucagon, to enhance energy uptake, storage, and expenditure through synergistic mechanisms (PMID 41054801).

Human evidence so far

In a phase 1b trial involving Chinese adults with overweight or obesity, mazdutide administered once-weekly subcutaneously led to body weight loss up to 6.4% over 12 weeks at doses up to 6 mg (human study) (PMID 36247927). Higher doses of mazdutide (9 mg and 10 mg) were further explored in this trial for safety and efficacy over 12 to 16 weeks (human study) (PMID 36247927). No serious adverse events were reported, and treatment-emergent adverse events were mild or moderate, primarily including upper respiratory tract infection, diarrhea, decreased appetite, nausea, urinary tract infection, abdominal distension, and vomiting (human study) (PMID 36247927).

A phase 3, double-blind, placebo-controlled trial in China involving 610 adults with overweight or obesity reported significant weight reduction (human study). At week 32, participants receiving 4 mg of mazdutide had a mean body weight change of -10.09%, and those receiving 6 mg had -12.55%, compared to 0.45% in the placebo group (human study) (PMID 40421736). At week 48, the mean body weight changes were -11.00% for 4 mg mazdutide and -14.01% for 6 mg mazdutide, versus 0.30% for placebo (human study) (PMID 40421736). A weight reduction of at least 15% at week 48 was observed in 35.7% of participants in the 4 mg group and 49.5% in the 6 mg group, compared to 2.0% in the placebo group (human study) (PMID 40421736). Beneficial effects were also seen on all prespecified cardiometabolic measures (human study) (PMID 40421736). The most frequent adverse events were gastrointestinal and mostly mild to moderate (human study) (PMID 40421736).

In a network meta-analysis of randomized controlled trials involving patients with obesity or overweight, mazdutide (6 or 4.5 mg) was among the GLP-1 receptor agonists and polyagonists studied for weight loss (human study) (PMID 39305981). Emerging agents, including mazdutide, may produce similar or greater reductions in weight (13.1-14.6%) compared to other weight loss drugs at one year, though with very low to low certainty of evidence (human study) (PMID 42419792).

Mazdutide is also under clinical evaluation for metabolic dysfunction-associated fatty liver disease, obstructive sleep apnea, and alcohol use disorder (human study) (PMID 41028652).

Open questions and limitations

While emerging pharmacotherapies for obesity, including incretin analogs like mazdutide, show promising results in phase 2 trials, more data are needed on mortality and obesity-related complications, such as cardio-renal-metabolic events (human study) (PMID 39952695). Long-term follow-up data on safety and efficacy for weight maintenance are also required (human study) (PMID 39952695).

Studies focusing on underrepresented populations, cost-effectiveness assessments, and drug availability are needed to address the care gap for patients with obesity (PMID 39952695).

Key terms explained

**GLP-1 receptor dual agonist**: A type of drug that activates two specific receptors in the body: the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor. Activating these receptors can influence appetite, metabolism, and blood sugar levels (PMID 36247927, PMID 40421736, PMID 41054801).

**BMI (Body-Mass Index)**: A measure that uses a person's weight and height to estimate body fat. It is calculated as weight in kilograms divided by the square of height in meters (PMID 40421736).

**Overweight or obesity**: Categories of BMI. Overweight is typically defined by a BMI of 24 to less than 28 kg/m² with at least one weight-related condition or ≥28 kg/m², while obesity is defined by a BMI of at least 28 kg/m² (PMID 40421736, PMID 41028652).

**Cardiometabolic measures**: Indicators related to heart health and metabolism, such as blood pressure, cholesterol levels, and blood glucose (PMID 40421736).

**Type 2 diabetes (T2D)**: A chronic condition where the body either doesn't produce enough insulin or doesn't use insulin well, leading to high blood sugar levels (PMID 41028652).