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Peptide profile

Metabolic Fat loss Cardiovascular Clinical evidence

Mazdutide

Dual GLP-1/glucagon agonist for metabolic health · also known as IBI362, OXM3, Oxyntomodulin Analog 3

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Summary

Mazdutide is a dual GLP-1/glucagon receptor co-agonist peptide developed by Innovent Biologics, originally derived from oxyntomodulin. It simultaneously activates both GLP-1 and glucagon receptors to produce robust reductions in body weight, blood glucose, and hepatic fat. Clinical trials in China have demonstrated significant efficacy for obesity and type 2 diabetes management.

Typical dose
3–9 mg once weekly (clinical trial doses); research use typically 3–6 mg/week
Half-life
~7 days (once-weekly dosing supported)
Route
Subcutaneous
Cycle length
12–24 weeks (based on clinical trial durations)

Mechanism

How it works

Mazdutide binds and activates both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) with balanced agonism. GLP-1R activation enhances glucose-dependent insulin secretion, reduces glucagon release, slows gastric emptying, and suppresses appetite via central hypothalamic pathways. Concurrent GCGR activation increases energy expenditure through thermogenesis, hepatic fatty acid oxidation, and lipolysis, amplifying weight loss and metabolic benefits beyond GLP-1 mono-agonism alone.

Reported in research

Benefits

  • Significant body weight reduction (up to 10-15% in clinical trials at higher doses)
  • Improved glycemic control and reduced HbA1c in type 2 diabetes patients
  • Reduction in hepatic fat content and improvement in MASLD/NASH markers
  • Favorable improvements in cardiovascular risk factors including blood pressure, lipids, and waist circumference

Context, not a prescription

Dosing

Typical range
3–9 mg once weekly (clinical trial doses); research use typically 3–6 mg/week (Subcutaneous)
Cycle length
12–24 weeks (based on clinical trial durations)
Half-life
~7 days (once-weekly dosing supported)

Safety

Side effects & contraindications

Possible side effects

  • Nausea (most common, especially during dose escalation)
  • Vomiting
  • Diarrhea or constipation
  • Decreased appetite progressing to reduced caloric intake
  • Injection site reactions (mild erythema or irritation)
  • Transient elevations in heart rate

Contraindications

  • Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia type 2 (MEN2)
  • History of pancreatitis
  • Severe renal or hepatic impairment (limited safety data)
  • Pregnancy or breastfeeding
  • Known hypersensitivity to the compound or any excipient

Research information, not medical advice. Always consult a licensed clinician before considering any peptide.

In depth

Full profile

What it does

You'll likely notice feeling full faster at meals, fewer food cravings, gradually decreasing body weight, and potentially more stable energy levels throughout the day. Blood sugar improvements happen even before significant weight loss.

How it works

Imagine your metabolism is a car that's been running sluggishly. GLP-1 is the GPS that stops you from taking detours to the snack cupboard, while glucagon is the turbo boost that makes the engine burn fuel faster. Mazdutide presses both at once, getting you to your destination — fat loss and better blood sugar — much faster than either alone.

After a weekly injection under the skin, Mazdutide slowly releases into your bloodstream. It tells your brain you're full sooner, slows down how fast food leaves your stomach, helps your pancreas release the right amount of insulin after meals, and tells your liver to burn stored fat for energy — all at the same time.

What to expect

Most people notice reduced appetite within the first 1–2 weeks. Measurable weight loss typically appears within 4 weeks, with more significant changes by weeks 8–12.

  • Week 1–2: Appetite begins to decrease and you may feel full much faster than usual. Mild nausea is common as your body adjusts. Weight may not change significantly yet.
  • Weeks 2–8: Consistent weekly injections lead to progressive weight loss, often 1–2 kg per month. Blood sugar levels start improving. Nausea typically diminishes as your body adapts.
  • Weeks 8–24: More significant weight reduction (potentially 8–15% of body weight in clinical studies at therapeutic doses). Improvements in energy levels, waist circumference, blood lipids, and blood pressure become measurable.

Good to know

  • Start at the lowest dose and increase slowly (dose escalation over weeks) to minimize GI side effects
  • Take injections at the same time each week, with or after a meal to reduce nausea
  • Stay well hydrated and eat smaller, more frequent meals during the adjustment period
  • Monitor your blood sugar if you are also taking insulin or sulfonylureas to avoid hypoglycemia

Staying safe

  • Nausea, especially in the first few weeks or after dose increases
  • Mild digestive upset including loose stools or constipation
  • Reduced appetite (desired effect that can sometimes feel uncomfortable)

Avoid if you have:

  • Anyone with a personal or family history of thyroid cancer (specifically medullary thyroid carcinoma)
  • People who have had pancreatitis
  • Pregnant or breastfeeding women
  • People with type 1 diabetes without medical supervision

Overview

Documented physiological changes include: dose-dependent reductions in body weight (3 mg/week ~6–8%; 6 mg/week ~10–12%; 9 mg/week ~13–15% at 24 weeks in Phase 2), HbA1c reductions of 1.5–2.5% in T2D cohorts, significant hepatic fat fraction reduction measured by MRI-PDFF, reductions in waist circumference, triglycerides, LDL-C, and systolic blood pressure. Modest increases in resting heart rate (~2–5 bpm) have been observed, consistent with GCGR agonism.

How it works

Mazdutide operates like a dual-key ignition system in metabolic physiology: the GLP-1R key throttles down caloric input by reprogramming hypothalamic feeding circuits and slowing nutrient absorption, while the GCGR key opens the afterburner on hepatic and adipose fuel combustion. Unlike tirzepatide, which combines GLP-1R with GIP receptor agonism (primarily amplifying insulin secretion), Mazdutide's GCGR component directly increases energy expenditure — a mechanistically distinct and potentially complementary thermogenic pathway.

Following subcutaneous injection, Mazdutide's fatty acid side chain mediates reversible albumin binding, extending plasma half-life to approximately 7 days and supporting once-weekly dosing. Peak plasma concentrations (Tmax) occur at approximately 24–72 hours post-injection. The compound distributes to GLP-1R-expressing tissues including pancreas, gut, brain (area postrema, hypothalamus), and GCGR-expressing tissues including liver and adipose tissue. Hepatic GCGR activation reduces steatosis via enhanced β-oxidation and reduced de novo lipogenesis, supported by preliminary biomarker and imaging data from Phase 2 trials. Renal clearance and proteolytic degradation are the primary elimination pathways.

Onset & timeline

Pharmacodynamic appetite suppression begins within 24–48 hours of the first dose as plasma levels rise. Glycemic effects in T2D patients (reduced fasting glucose, postprandial glucose excursion) are measurable within 1–2 weeks. Statistically significant weight loss versus placebo emerges by weeks 4–8 in Phase 2 data. Full pharmacokinetic steady state is achieved after approximately 4–5 weekly doses (~4–5 weeks).

  • Days 1–7 (Week 1): Initial dose administered. Plasma levels rise toward Tmax (~24–72h). GLP-1R-mediated gastric emptying delay and appetite suppression begin. Nausea most likely in this window. No significant weight change expected; glycemic improvements in T2D may begin within first 48–72 hours.
  • Weeks 1–4: Pharmacokinetic accumulation progresses toward steady state (achieved ~4–5 weeks). Progressive appetite reduction with decreased caloric intake. Measurable fasting glucose improvements and initial HbA1c trajectory changes in T2D. Early weight loss (~1–3%) may be detectable. Nausea typically diminishes as GI tolerance improves.
  • Weeks 4–24: Sustained dual GLP-1R/GCGR agonism drives continued weight loss trajectory. Phase 2 data demonstrate 10–15% body weight reduction at 24 weeks with 6–9 mg/week doses. Hepatic fat content decreases measurably on MRI-PDFF. Cardiometabolic risk markers (blood pressure, lipids, waist circumference) improve in parallel. Phase 3 trials (GLORY program) are ongoing to confirm cardiovascular outcomes.

Getting the most from it

  • Implement a structured dose escalation protocol (e.g., start at 1–2 mg/week, increase by 1–2 mg every 2–4 weeks) to minimize GI adverse events and improve tolerability
  • Monitor fasting glucose and HbA1c every 4–8 weeks; adjust hypoglycemic co-medications proactively
  • Assess lipase and amylase at baseline; discontinue if symptomatic pancreatitis is suspected
  • Use right lower abdomen, thigh, or upper arm for injection rotation to minimize site reactions
  • Screen for history of thyroid carcinoma and perform thyroid palpation at baseline per class precautions

Common side effects

  • Nausea (incidence ~40–60% during dose escalation, declining to ~15–20% at steady state)
  • Vomiting (10–25% during escalation)
  • Diarrhea and constipation (alternating in some subjects, ~15–20%)
  • Decreased appetite extending to anorexia at higher doses (~20–30%)
  • Transient heart rate elevation (GCGR-mediated sympathomimetic effect, ~2–5 bpm above baseline)

Mechanism of action

Mazdutide (IBI362/OXM3) is a structurally optimized oxyntomodulin-derived peptide engineered with fatty acid conjugation for extended half-life, enabling once-weekly subcutaneous dosing. It exerts balanced agonism at the GLP-1 receptor (GLP-1R, a class B GPCR) and glucagon receptor (GCGR), activating adenylyl cyclase via Gαs coupling to elevate intracellular cAMP. At GLP-1R, this potentiates glucose-dependent insulinotropic signaling in pancreatic β-cells, suppresses glucagon from α-cells, delays gastric emptying, and activates hypothalamic POMC/CART neurons to reduce food intake. At GCGR, concurrent signaling upregulates hepatic fatty acid β-oxidation via PPARα, stimulates brown adipose tissue thermogenesis via sympathetic activation, and promotes lipolysis in white adipose tissue. The net result is a synergistic metabolic phenotype: reduced caloric intake from GLP-1R satiety signaling combined with increased energy expenditure from GCGR-driven thermogenesis — two mechanisms rarely achieved simultaneously by mono-agonists.

Following subcutaneous injection, Mazdutide's fatty acid side chain mediates reversible albumin binding, extending plasma half-life to approximately 7 days and supporting once-weekly dosing. Peak plasma concentrations (Tmax) occur at approximately 24–72 hours post-injection. The compound distributes to GLP-1R-expressing tissues including pancreas, gut, brain (area postrema, hypothalamus), and GCGR-expressing tissues including liver and adipose tissue. Hepatic GCGR activation reduces steatosis via enhanced β-oxidation and reduced de novo lipogenesis, supported by preliminary biomarker and imaging data from Phase 2 trials. Renal clearance and proteolytic degradation are the primary elimination pathways.

Pharmacodynamics

Pharmacodynamic appetite suppression begins within 24–48 hours of the first dose as plasma levels rise. Glycemic effects in T2D patients (reduced fasting glucose, postprandial glucose excursion) are measurable within 1–2 weeks. Statistically significant weight loss versus placebo emerges by weeks 4–8 in Phase 2 data. Full pharmacokinetic steady state is achieved after approximately 4–5 weekly doses (~4–5 weeks).

Documented physiological changes include: dose-dependent reductions in body weight (3 mg/week ~6–8%; 6 mg/week ~10–12%; 9 mg/week ~13–15% at 24 weeks in Phase 2), HbA1c reductions of 1.5–2.5% in T2D cohorts, significant hepatic fat fraction reduction measured by MRI-PDFF, reductions in waist circumference, triglycerides, LDL-C, and systolic blood pressure. Modest increases in resting heart rate (~2–5 bpm) have been observed, consistent with GCGR agonism.

Timeline

  • Days 1–7 (Week 1): Initial dose administered. Plasma levels rise toward Tmax (~24–72h). GLP-1R-mediated gastric emptying delay and appetite suppression begin. Nausea most likely in this window. No significant weight change expected; glycemic improvements in T2D may begin within first 48–72 hours.
  • Weeks 1–4: Pharmacokinetic accumulation progresses toward steady state (achieved ~4–5 weeks). Progressive appetite reduction with decreased caloric intake. Measurable fasting glucose improvements and initial HbA1c trajectory changes in T2D. Early weight loss (~1–3%) may be detectable. Nausea typically diminishes as GI tolerance improves.
  • Weeks 4–24: Sustained dual GLP-1R/GCGR agonism drives continued weight loss trajectory. Phase 2 data demonstrate 10–15% body weight reduction at 24 weeks with 6–9 mg/week doses. Hepatic fat content decreases measurably on MRI-PDFF. Cardiometabolic risk markers (blood pressure, lipids, waist circumference) improve in parallel. Phase 3 trials (GLORY program) are ongoing to confirm cardiovascular outcomes.

Comparisons

  • Mazdutide (GLP-1R/GCGR) — effectiveness High, safety Moderate, cost $$$, Medium to use
  • Tirzepatide (GLP-1R/GIPR) — effectiveness Very High, safety Good, cost $$$$, Medium to use
  • Semaglutide 2.4mg (GLP-1R) — effectiveness High, safety Good, cost $$$$, Medium to use
  • Liraglutide 3.0mg (GLP-1R) — effectiveness Moderate, safety Good, cost $$$, Low to use

Adverse effects

Common:

  • Nausea (incidence ~40–60% during dose escalation, declining to ~15–20% at steady state)
  • Vomiting (10–25% during escalation)
  • Diarrhea and constipation (alternating in some subjects, ~15–20%)
  • Decreased appetite extending to anorexia at higher doses (~20–30%)
  • Transient heart rate elevation (GCGR-mediated sympathomimetic effect, ~2–5 bpm above baseline)

Rare:

  • Acute pancreatitis (<1%, causality not definitively established in current trial data)
  • Cholelithiasis / gallstone formation (class effect of GLP-1R agonists, mechanism involves reduced gallbladder motility)
  • Hypoglycemia (rare in monotherapy; risk increases with concomitant insulin secretagogues or insulin)
  • Injection site nodules or lipohypertrophy with chronic use

Contraindications & risk mitigation

Contraindicated in:

  • Patients with personal or family history of MTC or MEN2 syndrome (rodent thyroid C-cell hyperplasia observed with GLP-1R agonist class; human relevance uncertain but contraindicated by class precaution)
  • Active or recent history of pancreatitis
  • Patients with severe hepatic impairment (Child-Pugh C) — pharmacokinetic data insufficient
  • Patients with significant cardiac arrhythmia history where heart rate elevation is poorly tolerated
  • Patients on concomitant insulin or sulfonylurea without glucose monitoring protocols
  • Implement a structured dose escalation protocol (e.g., start at 1–2 mg/week, increase by 1–2 mg every 2–4 weeks) to minimize GI adverse events and improve tolerability
  • Monitor fasting glucose and HbA1c every 4–8 weeks; adjust hypoglycemic co-medications proactively
  • Assess lipase and amylase at baseline; discontinue if symptomatic pancreatitis is suspected
  • Use right lower abdomen, thigh, or upper arm for injection rotation to minimize site reactions
  • Screen for history of thyroid carcinoma and perform thyroid palpation at baseline per class precautions

Qué hace

You'll likely notice feeling full faster at meals, fewer food cravings, gradually decreasing body weight, and potentially more stable energy levels throughout the day. Blood sugar improvements happen even before significant weight loss.

Cómo funciona

Imagine your metabolism is a car that's been running sluggishly. GLP-1 is the GPS that stops you from taking detours to the snack cupboard, while glucagon is the turbo boost that makes the engine burn fuel faster. Mazdutide presses both at once, getting you to your destination — fat loss and better blood sugar — much faster than either alone.

After a weekly injection under the skin, Mazdutide slowly releases into your bloodstream. It tells your brain you're full sooner, slows down how fast food leaves your stomach, helps your pancreas release the right amount of insulin after meals, and tells your liver to burn stored fat for energy — all at the same time.

Qué esperar

Most people notice reduced appetite within the first 1–2 weeks. Measurable weight loss typically appears within 4 weeks, with more significant changes by weeks 8–12.

  • Week 1–2: Appetite begins to decrease and you may feel full much faster than usual. Mild nausea is common as your body adjusts. Weight may not change significantly yet.
  • Weeks 2–8: Consistent weekly injections lead to progressive weight loss, often 1–2 kg per month. Blood sugar levels start improving. Nausea typically diminishes as your body adapts.
  • Weeks 8–24: More significant weight reduction (potentially 8–15% of body weight in clinical studies at therapeutic doses). Improvements in energy levels, waist circumference, blood lipids, and blood pressure become measurable.

Bueno saber

  • Start at the lowest dose and increase slowly (dose escalation over weeks) to minimize GI side effects
  • Take injections at the same time each week, with or after a meal to reduce nausea
  • Stay well hydrated and eat smaller, more frequent meals during the adjustment period
  • Monitor your blood sugar if you are also taking insulin or sulfonylureas to avoid hypoglycemia

Manteniéndose seguro

  • Nausea, especially in the first few weeks or after dose increases
  • Mild digestive upset including loose stools or constipation
  • Reduced appetite (desired effect that can sometimes feel uncomfortable)

Evitar si tienes:

  • Anyone with a personal or family history of thyroid cancer (specifically medullary thyroid carcinoma)
  • People who have had pancreatitis
  • Pregnant or breastfeeding women
  • People with type 1 diabetes without medical supervision

Descripción general

Documented physiological changes include: dose-dependent reductions in body weight (3 mg/week ~6–8%; 6 mg/week ~10–12%; 9 mg/week ~13–15% at 24 weeks in Phase 2), HbA1c reductions of 1.5–2.5% in T2D cohorts, significant hepatic fat fraction reduction measured by MRI-PDFF, reductions in waist circumference, triglycerides, LDL-C, and systolic blood pressure. Modest increases in resting heart rate (~2–5 bpm) have been observed, consistent with GCGR agonism.

Cómo funciona

Mazdutide operates like a dual-key ignition system in metabolic physiology: the GLP-1R key throttles down caloric input by reprogramming hypothalamic feeding circuits and slowing nutrient absorption, while the GCGR key opens the afterburner on hepatic and adipose fuel combustion. Unlike tirzepatide, which combines GLP-1R with GIP receptor agonism (primarily amplifying insulin secretion), Mazdutide's GCGR component directly increases energy expenditure — a mechanistically distinct and potentially complementary thermogenic pathway.

Following subcutaneous injection, Mazdutide's fatty acid side chain mediates reversible albumin binding, extending plasma half-life to approximately 7 days and supporting once-weekly dosing. Peak plasma concentrations (Tmax) occur at approximately 24–72 hours post-injection. The compound distributes to GLP-1R-expressing tissues including pancreas, gut, brain (area postrema, hypothalamus), and GCGR-expressing tissues including liver and adipose tissue. Hepatic GCGR activation reduces steatosis via enhanced β-oxidation and reduced de novo lipogenesis, supported by preliminary biomarker and imaging data from Phase 2 trials. Renal clearance and proteolytic degradation are the primary elimination pathways.

Inicio y cronología

Pharmacodynamic appetite suppression begins within 24–48 hours of the first dose as plasma levels rise. Glycemic effects in T2D patients (reduced fasting glucose, postprandial glucose excursion) are measurable within 1–2 weeks. Statistically significant weight loss versus placebo emerges by weeks 4–8 in Phase 2 data. Full pharmacokinetic steady state is achieved after approximately 4–5 weekly doses (~4–5 weeks).

  • Days 1–7 (Week 1): Initial dose administered. Plasma levels rise toward Tmax (~24–72h). GLP-1R-mediated gastric emptying delay and appetite suppression begin. Nausea most likely in this window. No significant weight change expected; glycemic improvements in T2D may begin within first 48–72 hours.
  • Weeks 1–4: Pharmacokinetic accumulation progresses toward steady state (achieved ~4–5 weeks). Progressive appetite reduction with decreased caloric intake. Measurable fasting glucose improvements and initial HbA1c trajectory changes in T2D. Early weight loss (~1–3%) may be detectable. Nausea typically diminishes as GI tolerance improves.
  • Weeks 4–24: Sustained dual GLP-1R/GCGR agonism drives continued weight loss trajectory. Phase 2 data demonstrate 10–15% body weight reduction at 24 weeks with 6–9 mg/week doses. Hepatic fat content decreases measurably on MRI-PDFF. Cardiometabolic risk markers (blood pressure, lipids, waist circumference) improve in parallel. Phase 3 trials (GLORY program) are ongoing to confirm cardiovascular outcomes.

Cómo aprovecharlo al máximo

  • Implement a structured dose escalation protocol (e.g., start at 1–2 mg/week, increase by 1–2 mg every 2–4 weeks) to minimize GI adverse events and improve tolerability
  • Monitor fasting glucose and HbA1c every 4–8 weeks; adjust hypoglycemic co-medications proactively
  • Assess lipase and amylase at baseline; discontinue if symptomatic pancreatitis is suspected
  • Use right lower abdomen, thigh, or upper arm for injection rotation to minimize site reactions
  • Screen for history of thyroid carcinoma and perform thyroid palpation at baseline per class precautions

Efectos secundarios comunes

  • Nausea (incidence ~40–60% during dose escalation, declining to ~15–20% at steady state)
  • Vomiting (10–25% during escalation)
  • Diarrhea and constipation (alternating in some subjects, ~15–20%)
  • Decreased appetite extending to anorexia at higher doses (~20–30%)
  • Transient heart rate elevation (GCGR-mediated sympathomimetic effect, ~2–5 bpm above baseline)

Mecanismo de acción

Mazdutide (IBI362/OXM3) is a structurally optimized oxyntomodulin-derived peptide engineered with fatty acid conjugation for extended half-life, enabling once-weekly subcutaneous dosing. It exerts balanced agonism at the GLP-1 receptor (GLP-1R, a class B GPCR) and glucagon receptor (GCGR), activating adenylyl cyclase via Gαs coupling to elevate intracellular cAMP. At GLP-1R, this potentiates glucose-dependent insulinotropic signaling in pancreatic β-cells, suppresses glucagon from α-cells, delays gastric emptying, and activates hypothalamic POMC/CART neurons to reduce food intake. At GCGR, concurrent signaling upregulates hepatic fatty acid β-oxidation via PPARα, stimulates brown adipose tissue thermogenesis via sympathetic activation, and promotes lipolysis in white adipose tissue. The net result is a synergistic metabolic phenotype: reduced caloric intake from GLP-1R satiety signaling combined with increased energy expenditure from GCGR-driven thermogenesis — two mechanisms rarely achieved simultaneously by mono-agonists.

Following subcutaneous injection, Mazdutide's fatty acid side chain mediates reversible albumin binding, extending plasma half-life to approximately 7 days and supporting once-weekly dosing. Peak plasma concentrations (Tmax) occur at approximately 24–72 hours post-injection. The compound distributes to GLP-1R-expressing tissues including pancreas, gut, brain (area postrema, hypothalamus), and GCGR-expressing tissues including liver and adipose tissue. Hepatic GCGR activation reduces steatosis via enhanced β-oxidation and reduced de novo lipogenesis, supported by preliminary biomarker and imaging data from Phase 2 trials. Renal clearance and proteolytic degradation are the primary elimination pathways.

Farmacodinamia

Pharmacodynamic appetite suppression begins within 24–48 hours of the first dose as plasma levels rise. Glycemic effects in T2D patients (reduced fasting glucose, postprandial glucose excursion) are measurable within 1–2 weeks. Statistically significant weight loss versus placebo emerges by weeks 4–8 in Phase 2 data. Full pharmacokinetic steady state is achieved after approximately 4–5 weekly doses (~4–5 weeks).

Documented physiological changes include: dose-dependent reductions in body weight (3 mg/week ~6–8%; 6 mg/week ~10–12%; 9 mg/week ~13–15% at 24 weeks in Phase 2), HbA1c reductions of 1.5–2.5% in T2D cohorts, significant hepatic fat fraction reduction measured by MRI-PDFF, reductions in waist circumference, triglycerides, LDL-C, and systolic blood pressure. Modest increases in resting heart rate (~2–5 bpm) have been observed, consistent with GCGR agonism.

Cronología

  • Days 1–7 (Week 1): Initial dose administered. Plasma levels rise toward Tmax (~24–72h). GLP-1R-mediated gastric emptying delay and appetite suppression begin. Nausea most likely in this window. No significant weight change expected; glycemic improvements in T2D may begin within first 48–72 hours.
  • Weeks 1–4: Pharmacokinetic accumulation progresses toward steady state (achieved ~4–5 weeks). Progressive appetite reduction with decreased caloric intake. Measurable fasting glucose improvements and initial HbA1c trajectory changes in T2D. Early weight loss (~1–3%) may be detectable. Nausea typically diminishes as GI tolerance improves.
  • Weeks 4–24: Sustained dual GLP-1R/GCGR agonism drives continued weight loss trajectory. Phase 2 data demonstrate 10–15% body weight reduction at 24 weeks with 6–9 mg/week doses. Hepatic fat content decreases measurably on MRI-PDFF. Cardiometabolic risk markers (blood pressure, lipids, waist circumference) improve in parallel. Phase 3 trials (GLORY program) are ongoing to confirm cardiovascular outcomes.

Comparaciones

  • Mazdutide (GLP-1R/GCGR) — efectividad High, seguridad Moderate, costo $$$, Medium de usar
  • Tirzepatide (GLP-1R/GIPR) — efectividad Very High, seguridad Good, costo $$$$, Medium de usar
  • Semaglutide 2.4mg (GLP-1R) — efectividad High, seguridad Good, costo $$$$, Medium de usar
  • Liraglutide 3.0mg (GLP-1R) — efectividad Moderate, seguridad Good, costo $$$, Low de usar

Efectos adversos

Comunes:

  • Nausea (incidence ~40–60% during dose escalation, declining to ~15–20% at steady state)
  • Vomiting (10–25% during escalation)
  • Diarrhea and constipation (alternating in some subjects, ~15–20%)
  • Decreased appetite extending to anorexia at higher doses (~20–30%)
  • Transient heart rate elevation (GCGR-mediated sympathomimetic effect, ~2–5 bpm above baseline)

Raros:

  • Acute pancreatitis (<1%, causality not definitively established in current trial data)
  • Cholelithiasis / gallstone formation (class effect of GLP-1R agonists, mechanism involves reduced gallbladder motility)
  • Hypoglycemia (rare in monotherapy; risk increases with concomitant insulin secretagogues or insulin)
  • Injection site nodules or lipohypertrophy with chronic use

Contraindicaciones y mitigación de riesgos

Contraindicado en:

  • Patients with personal or family history of MTC or MEN2 syndrome (rodent thyroid C-cell hyperplasia observed with GLP-1R agonist class; human relevance uncertain but contraindicated by class precaution)
  • Active or recent history of pancreatitis
  • Patients with severe hepatic impairment (Child-Pugh C) — pharmacokinetic data insufficient
  • Patients with significant cardiac arrhythmia history where heart rate elevation is poorly tolerated
  • Patients on concomitant insulin or sulfonylurea without glucose monitoring protocols
  • Implement a structured dose escalation protocol (e.g., start at 1–2 mg/week, increase by 1–2 mg every 2–4 weeks) to minimize GI adverse events and improve tolerability
  • Monitor fasting glucose and HbA1c every 4–8 weeks; adjust hypoglycemic co-medications proactively
  • Assess lipase and amylase at baseline; discontinue if symptomatic pancreatitis is suspected
  • Use right lower abdomen, thigh, or upper arm for injection rotation to minimize site reactions
  • Screen for history of thyroid carcinoma and perform thyroid palpation at baseline per class precautions

Reference data

Specifications

Molecular formula
C174H271N47O52S2
Molecular weight
~3,900 Da (approximate; exact weight varies by salt form)
Half-life
~7 days (once-weekly dosing supported)
Route
Subcutaneous
Cycle length
12–24 weeks (based on clinical trial durations)
Storage
Store lyophilized powder at 2–8°C (refrigerated). Protect from light and moisture. Once reconstituted, use within 28 days if refrigerated. Do not freeze reconstituted solution. Avoid repeated freeze-thaw cycles.
Legal status
Investigational drug; not approved by the FDA or EMA. Approved for clinical trials in China. Available as a research compound in some jurisdictions. Not for human therapeutic use outside of approved clinical trials.

FAQ

Common questions

How does Mazdutide's dual GLP-1R/GCGR mechanism compare mechanistically to tirzepatide's GLP-1R/GIPR dual agonism?

Tirzepatide (GLP-1R/GIPR) primarily amplifies insulin secretion through GIP receptor co-stimulation and may improve adipocyte insulin sensitivity via GIPR signaling in adipose tissue. Mazdutide's GCGR component instead directly drives hepatic β-oxidation, brown adipose thermogenesis, and lipolysis — increasing energy expenditure rather than primarily modulating insulin. This means Mazdutide may have particular advantage in fatty liver disease and thermogenic weight loss, while tirzepatide may have superior glycemic control in insulin-resistant T2D. Direct head-to-head data are not yet available.

What is the significance of the GCGR component given that glucagon typically raises blood glucose?

The apparent paradox of GCGR agonism in a metabolic therapy is resolved by the co-dominant GLP-1R signaling: GLP-1R activation potently suppresses glucagon's glycogenolytic effects and enhances glucose-dependent insulin secretion, maintaining glycemic stability even in the presence of GCGR activation. The net effect is euglycemic or hypoglycemic relative to monotherapy, with the GCGR component primarily contributing to energy expenditure and hepatic lipid metabolism rather than adverse glycemic excursion. This balance has been confirmed in Phase 2 data with no significant hyperglycemia signals.

What Phase 3 trial data are available for Mazdutide?

As of early 2025, Innovent Biologics has initiated the GLORY Phase 3 program in China, studying Mazdutide in obesity, T2D, and MASLD/NASH populations. Interim Phase 2 data published in The Lancet Diabetes & Endocrinology (2023) showed significant dose-dependent weight loss and glycemic improvements. Full Phase 3 efficacy and cardiovascular outcomes data are anticipated by 2025–2026. Global regulatory submissions outside China have not yet been announced.

What is the evidence level?

This compound is classified as Clinical evidence. Randomized controlled trial data in humans exists and supports use in specific contexts.

Research

Research & sources

Clinical evidence

Current evidence for Mazdutide is rated as Clinical evidence. Human clinical evidence supports the reported effects.

  1. 1. Once-weekly IBI362 (mazdutide) in Chinese adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, multiple-dose, phase 2 trial (2023) — The Lancet Diabetes & Endocrinology, DOI: 10.1016/S2213-8587(23)00191-4
  2. 2. IBI362 Phase 2 trial in type 2 diabetes mellitus — ClinicalTrials.gov registry (2022) — ClinicalTrials.gov Identifier: NCT04432844
  3. 3. Dual GLP-1/glucagon receptor agonism for metabolic disease: mechanistic rationale and clinical development landscape (2022) — Nature Reviews Drug Discovery (review article)
  4. 4. Oxyntomodulin and related peptides as metabolic regulators: from physiology to pharmacology (2021) — Diabetes, Obesity and Metabolism

Explore

Often discussed alongside

Semaglutide · fat-loss Tirzepatide · fat-loss BPC-157 · healing AOD-9604 · fat-loss