Mazdutide (IBI362)

Q: How much weight does mazdutide cause compared to semaglutide?

Mazdutide demonstrated 20.1% weight loss over 60 weeks in Phase 3 trials (GLORY-2), with 48.7% of users achieving ≥20% reduction. This exceeded semaglutide's typical 12-17% losses. The dual GLP-1/glucagon mechanism accounts for superior weight loss and metabolic improvements.

Q: Why does mazdutide cause thermogenesis while semaglutide doesn't?

Mazdutide's glucagon receptor agonism increases energy expenditure and thermogenesis—burning calories actively rather than just reducing appetite. Semaglutide is GLP-1 only. This dual-agonist approach explains mazdutide's superior metabolic rate elevation.

Q: Is mazdutide safer than semaglutide for nausea?

Not necessarily. Both cause GLP-1-induced nausea early in treatment, though it typically improves with dose escalation. Mazdutide's additional heart rate increase (5-17 bpm) from glucagon agonism is a distinct side effect requiring cardiovascular monitoring.

Q: Can I switch from semaglutide to mazdutide?

Potentially, but with medical supervision. Both are GLP-1 agonists, so overlap during transition risks hypoglycemia and severe GI effects. Wait 1-2 weeks after stopping semaglutide before starting mazdutide, and monitor glucose carefully. Never combine them.

Dual GLP-1/Glucagon Receptor Agonist · Weight Loss & Diabetes

Overview

First-in-class dual GLP-1 and glucagon receptor agonist combining appetite suppression with thermogenesis stimulation. Phase 3 trials demonstrated superiority over semaglutide for weight loss and glycemic control.

Dual agonist activation: GLP-1 stimulates insulin, suppresses glucagon, slows gastric emptying; Glucagon increases energy expenditure and thermogenesis while GLP-1 counteracts glucose-raising effects.

GLORY-2 demonstrated 20.1% weight loss with 9mg over 60 weeks; 48.7% achieved ≥20% reduction.

Significant reductions in waist circumference, systolic BP (-7.57 mmHg), triglycerides (-43%).

Exploratory analysis showed 80.2% reduction in liver fat, suggesting MASLD/MASH benefits.

HbA1c reductions of 1.41-2.03% across trials; DREAMS-3 showed -2.03% vs semaglutide -1.84%.

Mechanism

GLORY-2 demonstrated 20.1% weight loss with 9mg over 60 weeks; 48.7% achieved ≥20% reduction.

Research areas

First-in-class dual GLP-1 and glucagon receptor agonist combining appetite suppression with thermogenesis stimulation. Phase 3 trials demonstrated superiority over semaglutide for weight loss and glycemic control.
Dual agonist activation: GLP-1 stimulates insulin, suppresses glucagon, slows gastric emptying; Glucagon increases energy expenditure and thermogenesis while GLP-1 counteracts glucose-raising effects.
GLORY-2 demonstrated 20.1% weight loss with 9mg over 60 weeks; 48.7% achieved ≥20% reduction.
Significant reductions in waist circumference, systolic BP (-7.57 mmHg), triglycerides (-43%).
Exploratory analysis showed 80.2% reduction in liver fat, suggesting MASLD/MASH benefits.
HbA1c reductions of 1.41-2.03% across trials; DREAMS-3 showed -2.03% vs semaglutide -1.84%.
48% achieved HbA1c <7.0% AND ≥10% weight loss versus 21% with semaglutide.
Systolic reduction of -7.57 mmHg, diastolic -2.98 mmHg in clinical trials.
Total cholesterol -16.82%, triglycerides -43.29%, LDL -17.07%.

Research notes

Nausea (mild-moderate, typically improves over time)
Diarrhea
Vomiting
Increased heart rate (5-17 bpm observed)
Severe or persistent abdominal pain (potential pancreatitis)
Neck lumps, hoarseness, or difficulty swallowing
Severe nausea/vomiting preventing adequate nutrition or hydration
Signs of severe hypoglycemia (confusion, sweating, shakiness)
Severe allergic reactions (rash, difficulty breathing, facial swelling)
Unusual mood changes, depression, or suicidal thoughts
Signs of gallbladder problems (severe upper right abdominal pain)
Personal or family history of medullary thyroid carcinoma
MEN2 syndrome history (class warning for GLP-1 agonists)
Pregnancy or breastfeeding (insufficient safety data)

FAQs

How much weight does mazdutide cause compared to semaglutide?

Mazdutide demonstrated 20.1% weight loss over 60 weeks in Phase 3 trials (GLORY-2), with 48.7% of users achieving ≥20% reduction. This exceeded semaglutide's typical 12-17% losses. The dual GLP-1/glucagon mechanism accounts for superior weight loss and metabolic improvements.

Why does mazdutide cause thermogenesis while semaglutide doesn't?

Mazdutide's glucagon receptor agonism increases energy expenditure and thermogenesis—burning calories actively rather than just reducing appetite. Semaglutide is GLP-1 only. This dual-agonist approach explains mazdutide's superior metabolic rate elevation.

Is mazdutide safer than semaglutide for nausea?

Not necessarily. Both cause GLP-1-induced nausea early in treatment, though it typically improves with dose escalation. Mazdutide's additional heart rate increase (5-17 bpm) from glucagon agonism is a distinct side effect requiring cardiovascular monitoring.

Can I switch from semaglutide to mazdutide?

Potentially, but with medical supervision. Both are GLP-1 agonists, so overlap during transition risks hypoglycemia and severe GI effects. Wait 1-2 weeks after stopping semaglutide before starting mazdutide, and monitor glucose carefully. Never combine them.