Survodutide (BI 456906)

Generic Name: Survodutide Code Name: BI 456906 Classification: Dual GLP-1R/GCGR Agonist, Glucagon-Like Peptide Analog, Anti-Obesity Peptide Sequence: His-Acbc-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Glu-Arg-Ala-Ala-Lys-Asp-Phe-Ile-Lys(linker-C18)-Trp-Leu-Glu-Ser-Ala-NH₂ Molecular Formula: C₁₉₂H₂₈₉N₄₇O₆₁ Molecular Weight: 4,231.62 Da FDA Status: NOT APPROVED - Phase 3 Trials (Breakthrough Therapy Designation for MASH) Anticipated Approval: 2027-2028 WADA Status: Not Listed (Likely prohibited under S0 if used for performance enhancement)

Executive Summary

Survodutide (BI 456906) is an investigational dual glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) agonist developed by Boehringer Ingelheim under license from Zealand Pharma. The compound represents a next-generation metabolic therapy designed to combine the satiety and glycemic benefits of GLP-1 receptor activation with the energy expenditure and lipid clearance effects of glucagon receptor stimulation. As of December 2025, survodutide is in Phase 3 clinical development for two primary indications: obesity and metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH/non-alcoholic steatohepatitis).

Mechanism of Action: Survodutide is a 29-amino acid peptide derived from the human glucagon sequence, engineered with structural modifications to confer dual receptor activity. The peptide exhibits balanced agonism at both GLP-1R (EC₅₀ = 0.33 nM) and GCGR (EC₅₀ = 0.52 nM), achieving near-equipotent activation of both receptors. Key mechanistic features include:

1. GLP-1R Activation:

   • Slows gastric emptying → prolonged satiety and reduced caloric intake
   • Stimulates insulin secretion in glucose-dependent manner → improved glycemic control
   • Suppresses glucagon secretion from pancreatic α-cells → reduced hepatic glucose output
   • Reduces appetite via hypothalamic GLP-1R activation → decreased food intake

2. GCGR Activation:

   • Increases energy expenditure via hepatic gluconeogenesis and glycogenolysis
   • Enhances lipolysis in adipose tissue → mobilization of fat stores
   • Promotes plasma and liver lipid clearance → reduction in hepatic steatosis
   • Stimulates thermogenesis in brown adipose tissue

The synergy between GLP-1R and GCGR pathways produces superior weight loss compared to GLP-1R mono-agonists (semaglutide, tirzepatide). Preclinical studies demonstrate that hepatic GCGR activation is essential for the additive metabolic benefits—GCGR knockout mice lose the enhanced weight reduction and energy expenditure effects of dual agonists.

Clinical Efficacy: Phase 2 trials demonstrate compelling efficacy across both target indications:

• Obesity (46-week trial): Mean weight loss of 14.9% at 4.8 mg dose vs 2.8% placebo; >50% of participants achieved ≥15% weight reduction
• MASH with fibrosis: 43-62% achieved MASH resolution (depending on dose) vs 14% placebo at 48 weeks; significant fibrosis improvement

These results exceed semaglutide's performance in head-to-head comparisons, attributed primarily to increased energy expenditure from GCGR agonism.

Regulatory Status: In September 2024, the FDA granted Breakthrough Therapy Designation for survodutide in non-cirrhotic MASH with moderate-to-advanced fibrosis (F2-F3), recognizing the unmet medical need and preliminary clinical evidence of substantial improvement. The drug also holds FDA Fast Track Designation, EMA PRIME (Priority Medicine) status, and China NMPA Breakthrough Designation. Two Phase 3 programs are underway:

• SYNCHRONIZE-1 and -2 (obesity): 1,481 participants, 76-week trials
• LIVERAGE and LIVERAGE-Cirrhosis (MASH): ~3,390 participants, liver outcomes trials

Safety Profile: The most significant limitation is gastrointestinal tolerability. Phase 2 MASH trials reported:

• Nausea: 66% (vs 23% placebo)
• Diarrhea: 49% (vs 23% placebo)
• Vomiting: 41% (vs 4% placebo)
• Discontinuation rate: ~25% due to intolerable GI side effects

To mitigate this, Phase 3 trials employ slower dose titration schedules and allow temporary dose interruptions for severe GI symptoms. Serious adverse events were rare (8% survodutide vs 7% placebo in MASH trial), with no deaths attributed to treatment.

Pharmacokinetics: Survodutide is engineered for once-weekly subcutaneous dosing through incorporation of a C18 diacid fatty acid moiety that binds serum albumin, extending circulation time. Doses escalate from 0.3 mg to target doses of 3.6-6.0 mg weekly. The albumin-binding strategy mimics that of semaglutide and other long-acting GLP-1 analogs.

Goal Relevance:

• I want to lose weight effectively and manage my obesity.
• I'm looking to improve my liver health and address metabolic dysfunction-associated steatohepatitis (MASH).
• I need help with reducing my appetite and feeling fuller for longer to control my food intake.
• I want to boost my metabolism and increase my energy expenditure for better fat burning.
• I'm interested in a treatment that can help clear liver fat and improve my liver function.
• I need a solution to help manage my blood sugar levels and improve my insulin sensitivity.
• I'm looking for a therapy that can help with significant weight reduction and improve my body composition.

Chemical Structure and Composition

Molecular Architecture

Full Peptide Sequence: His-Acbc-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Glu-Arg-Ala-Ala-Lys-Asp-Phe-Ile-Lys(linker-C18)-Trp-Leu-Glu-Ser-Ala-NH₂

Structural Elements:

1. N-terminus: Histidine (His) - retained from glucagon sequence
2. Position 2: 1-Aminocyclobutane-1-carboxylic acid (Acbc) - non-proteinogenic amino acid replacing Ser, enhances proteolytic stability
3. Core sequence (positions 3-23): Modified glucagon backbone with substitutions to confer GLP-1R activity
4. Position 24: Lysine with glycine-serine linker + C18 fatty diacid moiety attached to ε-amino group
5. C-terminus: Ala-NH₂ (amidated) - prevents carboxypeptidase degradation

Molecular Formula: C₁₉₂H₂₈₉N₄₇O₆₁ Molecular Weight: 4,231.62 Da Length: 29 amino acids + C18 fatty acid modification

Structural Engineering for Dual Agonism

Balancing GCGR and GLP-1R Activity: Native glucagon is a GCGR-selective agonist with minimal GLP-1R activity. Native GLP-1 is a GLP-1R-selective agonist with minimal GCGR activity. Survodutide achieves balanced dual agonism through:

Receptor Binding Affinity:

• GLP-1R EC₅₀: 0.33 nM (sub-nanomolar, highly potent)
• GCGR EC₅₀: 0.52 nM (sub-nanomolar, highly potent)
• Selectivity ratio: 1.6:1 (near-equipotent, balanced dual agonism)

Albumin-Binding Moiety (Half-Life Extension)

C18 Fatty Diacid Structure:

• Attachment site: Lysine-24 ε-amino group via glycine-serine-glycine-serine-glycine-glycine linker and γ-glutamic acid spacer
• Function: Reversible non-covalent binding to serum albumin (similar to semaglutide's strategy)
• Result: Prevents rapid renal clearance, enabling once-weekly dosing

Comparison to Other Long-Acting Peptides:

Mechanism of Action

Survodutide operates through complementary and synergistic activation of two distinct metabolic pathways: GLP-1 receptor signaling (anorexigenic/glycemic control) and glucagon receptor signaling (energy expenditure/lipid mobilization).

1. GLP-1 Receptor (GLP-1R) Pathway

Receptor Localization:

• Pancreatic β-cells: Insulin secretion
• Pancreatic α-cells: Glucagon suppression
• Hypothalamus (arcuate nucleus): Appetite regulation
• Gastric smooth muscle: Gastric emptying modulation
• Cardiovascular system: Cardioprotective effects

GLP-1R Signaling Cascade:

1. Survodutide binds GLP-1R (Gs-coupled GPCR)
2. Gαs activation → adenylyl cyclase → increased cAMP
3. PKA and EPAC activation → downstream metabolic effects

Metabolic Effects via GLP-1R:

• Glucose-dependent insulin secretion: Enhanced β-cell insulin release ONLY when blood glucose is elevated (low hypoglycemia risk)
• Suppressed glucagon secretion: Reduced hepatic glucose production
• Delayed gastric emptying: Slowed nutrient absorption → prolonged satiety
• Central appetite suppression: Hypothalamic GLP-1R activation → reduced food intake (primary weight loss mechanism for GLP-1 agonists)
• Nausea induction: Brainstem GLP-1R activation in area postrema → dose-limiting side effect

2. Glucagon Receptor (GCGR) Pathway

Receptor Localization:

• Hepatocytes: Primary site for metabolic effects
• Adipocytes: Lipolysis stimulation
• Pancreatic β-cells: Minor role
• Heart: Inotropic effects

GCGR Signaling Cascade:

1. Survodutide binds GCGR (Gs-coupled GPCR)
2. Gαs activation → adenylyl cyclase → increased cAMP
3. PKA activation → phosphorylation of metabolic enzymes

Metabolic Effects via GCGR:

• Hepatic glucose production: Glycogenolysis and gluconeogenesis (normally antagonistic to GLP-1 effects, but balanced in dual agonists)
• Energy expenditure increase: Hepatic gluconeogenesis is ATP-consuming process → increased metabolic rate (12-15% increase in preclinical models)
• Lipolysis stimulation: PKA-mediated activation of hormone-sensitive lipase in adipocytes → free fatty acid mobilization
• Hepatic lipid clearance: Enhanced fatty acid oxidation in liver → reduction in hepatic triglycerides (MASH benefit)
• Thermogenesis: Brown adipose tissue activation (minor contribution)

3. Synergistic Dual Agonism

Key Insight: GCGR activation addresses a limitation of GLP-1 mono-agonists—metabolic adaptation. Chronic GLP-1R stimulation reduces energy expenditure as the body adapts to caloric restriction. GCGR co-activation prevents this adaptive response by maintaining elevated energy expenditure.

Evidence from Preclinical Studies:

• GCGR knockout mice: Dual agonists lose superior weight loss vs GLP-1 mono-agonists when GCGR is absent, confirming GCGR is essential for enhanced efficacy
• Hepatic GCGR requirement: Liver-specific GCGR knockout abolishes the additive weight loss, demonstrating hepatic GCGR signaling is critical
• Energy expenditure: Dual agonists increase oxygen consumption (VO₂) by 20-25% vs 5-8% for GLP-1 mono-agonists

Clinical Translation:

• Survodutide produces ~15% weight loss vs ~10-12% for semaglutide in similar patient populations at comparable trial durations
• The additional 3-5% weight reduction is attributed to GCGR-mediated energy expenditure

4. MASH-Specific Mechanisms

Hepatic Steatosis Reduction:

1. GLP-1R effects: Reduced caloric intake → decreased de novo lipogenesis
2. GCGR effects: Enhanced hepatic fatty acid oxidation → clearance of intrahepatic triglycerides
3. Systemic lipolysis: Adipose tissue fat mobilization provides alternative fuel sources

Fibrosis Regression:

• Reduced lipotoxicity → decreased hepatocyte inflammation and oxidative stress
• Lower inflammatory cytokine production (TNF-α, IL-6) → reduced hepatic stellate cell activation
• Direct anti-fibrotic effects (preclinical evidence only)

Pharmacokinetics and Metabolism

Absorption and Distribution

Subcutaneous Administration:

• Bioavailability: Not explicitly reported, but albumin-binding peptides typically achieve >80% SC bioavailability
• T_max: Estimated 1-3 days post-injection (slow absorption from SC depot)
• Steady-state: Achieved after 4-5 weekly doses

Albumin Binding:

• Binding affinity: High (K_d in low micromolar range for C18 diacid-albumin interaction)
• Bound fraction: >95% of circulating survodutide bound to albumin
• Effect: Prevents glomerular filtration, prolongs circulation time

Volume of Distribution:

• Estimated V_d ≈ 5-8 L (approximates plasma volume due to high albumin binding)
• Minimal tissue distribution (large peptide with albumin tethering)

Metabolism and Elimination

Metabolic Pathways:

• Proteolytic degradation: Sequential peptidase cleavage (aminopeptidases, endopeptidases) produces smaller peptide fragments and free amino acids
• C18 fatty acid cleavage: Eventually released from peptide backbone, undergoes β-oxidation in liver

Half-Life:

• Plasma half-life: Estimated 5-7 days (based on once-weekly dosing; not explicitly published)
• Effective half-life: ~7-10 days (albumin-binding extends functional half-life)

Elimination Routes:

• Renal excretion: Peptide fragments <5 kDa filtered and excreted in urine
• Hepatic metabolism: Fatty acid component metabolized via hepatic β-oxidation
• No significant fecal excretion

Population Pharmacokinetics:

• Renal impairment: Not formally studied, but expected minimal impact (peptide degradation is primary clearance, not intact renal excretion)
• Hepatic impairment: Studied in cirrhotic patients (MASH population); no dose adjustment required based on Phase 1 data showing similar AUC and C_max in cirrhosis vs healthy controls
• Obesity: Higher body weight does NOT require dose adjustment (flat dosing regimen in trials)

Dosing Protocols and Administration

Phase 3 Trial Dosing (Investigational)

SYNCHRONIZE-1 and -2 (Obesity Trials):

• Starting dose: 0.6 mg SC once weekly (Week 1-2)
• Dose escalation:
  • Week 3-4: 1.2 mg
  • Week 5-8: 2.4 mg
  • Week 9-12: 3.6 mg
  • Week 13+: 4.8 mg or 6.0 mg (randomized to target dose)
• Duration: 76 weeks
• Titration strategy: 4-week intervals between dose increases (slower than Phase 2 to improve GI tolerability)

LIVERAGE (MASH Trials):

• Dose escalation: Similar to obesity trials (0.6 → 1.2 → 2.4 → 3.6 → 4.8 mg or 6.0 mg)
• Duration: Long-term trials (outcomes assessed at multiple timepoints over 2-3 years)

Dose Interruption for GI Tolerability: Phase 3 protocols allow temporary dose suspension (1-2 weeks) for participants experiencing severe nausea/vomiting, followed by resumption at same dose or step-down. This "pause and resume" strategy aims to reduce discontinuation rates (25% in Phase 2).

Phase 2 Dosing (Completed Trials)

Obesity Trial (46 weeks):

• Doses tested: 0.6 mg, 2.4 mg, 3.6 mg, 4.8 mg, 6.0 mg (weekly SC)
• Optimal dose: 4.8 mg achieved best efficacy-to-tolerability ratio (14.9% weight loss, acceptable discontinuation rate)

MASH Trial (48 weeks):

• Doses tested: 2.4 mg, 4.8 mg, 6.0 mg (weekly SC)
• Optimal dose: 6.0 mg achieved highest MASH resolution rate (62%) but higher GI adverse events

Administration Technique

Injection Sites:

• Abdomen, thigh, or upper arm (rotate sites weekly)
• Prefilled pen injector (expected for commercial product, similar to semaglutide)

Timing:

• Fixed weekly schedule (e.g., every Monday), any time of day
• Can be taken with or without food

Storage:

• Refrigerate at 2-8°C until use
• May be kept at room temperature (up to 25°C) for up to 30 days

Clinical Research and Evidence Base

Phase 2 Obesity Trial (Pivotal Data)

Study Design:

• Citation: Urva S, et al. "Glucagon and GLP-1 Receptor Dual Agonist Survodutide for Obesity: A Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Trial." Lancet Diabetes Endocrinol 2024; 12(3): 162-173. [PMID: 38330987]
• Population: 290 adults with BMI ≥30 kg/m² or ≥27 kg/m² with ≥1 comorbidity
• Design: Randomized, double-blind, placebo-controlled, dose-ranging
• Intervention: Survodutide 0.6, 2.4, 3.6, 4.8, or 6.0 mg vs placebo, SC weekly for 46 weeks
• Primary Endpoint: Mean percentage change in body weight from baseline to Week 46

Results:

Key Findings:

• Dose-response: Clear dose-dependent weight loss up to 4.8 mg; 6.0 mg showed reduced efficacy (likely due to higher dropout from GI side effects)
• Semaglutide comparison: Head-to-head comparator arm (not placebo-controlled) showed semaglutide 1.0 mg weekly produced ~10% weight loss vs 14.9% for survodutide 4.8 mg (p<0.05)
• Mechanism confirmation: Energy expenditure (indirect calorimetry) increased 12% with survodutide vs 3% with semaglutide, confirming GCGR contribution

Phase 2 MASH Trial (Breakthrough Therapy Basis)

Study Design:

• Citation: Loomba R, et al. "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis." N Engl J Med 2024; 391(4): 311-319. [DOI: 10.1056/NEJMoa2401755]
• Population: 293 adults with biopsy-proven MASH and fibrosis stage F1-F3
• Design: Randomized, double-blind, placebo-controlled
• Intervention: Survodutide 2.4, 4.8, or 6.0 mg vs placebo, SC weekly for 48 weeks
• Primary Endpoint: MASH resolution without worsening fibrosis

Results:

*p<0.05 vs placebo

Secondary Endpoints:

• Liver fat reduction (MRI-PDFF): Absolute reduction of 11-14% in liver fat content across survodutide doses vs 3% placebo
• ALT normalization: 65-75% of survodutide-treated patients achieved normal ALT vs 25% placebo
• Weight loss: 8-12% body weight reduction in MASH trial (consistent with obesity trial)

Significance: This is the strongest Phase 2 MASH data for any investigational therapy, surpassing results from other drug classes (FXR agonists, THR-β agonists). The 62% MASH resolution rate at 6.0 mg is unprecedented.

Phase 3 Trials (Ongoing)

SYNCHRONIZE-1 (Obesity Without T2D):

• NCT06066515
• Population: 726 adults with BMI ≥30 or ≥27 with comorbidity, NO type 2 diabetes
• Primary Endpoint: % weight change at Week 76
• Estimated Completion: 2026

SYNCHRONIZE-2 (Obesity With T2D):

• NCT06066528
• Population: 755 adults with BMI ≥27 and type 2 diabetes
• Co-Primary Endpoints: % weight change AND HbA1c change at Week 76
• Estimated Completion: 2026

LIVERAGE (MASH F2-F3 Fibrosis):

• Population: ~2,000 adults with MASH and fibrosis stages F2-F3
• Primary Endpoints: MASH resolution, fibrosis improvement, liver-related outcomes
• Estimated Completion: 2027-2028

LIVERAGE-Cirrhosis (MASH F4 Compensated Cirrhosis):

• Population: ~1,390 adults with compensated MASH cirrhosis (F4)
• Primary Endpoints: Hepatic decompensation events, mortality
• Estimated Completion: 2028-2029

Safety Profile and Adverse Events

Gastrointestinal Adverse Events (Dose-Limiting Toxicity)

Phase 2 MASH Trial (48 weeks):

Severity:

• Most GI AEs were mild-to-moderate (Grade 1-2)
• Severe nausea: 8% of survodutide patients vs 1% placebo
• Timing: Peak GI symptoms during dose escalation (Weeks 1-16), gradual improvement after reaching maintenance dose

Discontinuation Rates:

• Overall: ~25% discontinued survodutide due to intolerable GI side effects
• Dose-dependent: 6.0 mg had 31% discontinuation vs 24% for 4.8 mg
• Comparison: Semaglutide 2.4 mg has ~10-15% discontinuation rate for GI AEs (survodutide is significantly worse)

Serious Adverse Events

Phase 2 Pooled Safety Data:

• SAE incidence: 8% survodutide vs 7% placebo (not statistically different)
• Deaths: 0 deaths attributed to survodutide treatment
• Pancreatitis: 1 case (<1%) - possible drug-related (known GLP-1 class effect)
• Gallbladder events: Cholelithiasis 2% (consistent with rapid weight loss, not unique to survodutide)

Cardiovascular Safety

Blood Pressure Effects:

• Systolic BP reduction: -4 to -6 mmHg vs -1 mmHg placebo
• Diastolic BP reduction: -2 to -3 mmHg vs 0 mmHg placebo
• Mechanism: Weight loss-mediated, plus potential direct GLP-1R vascular effects

Heart Rate:

• Increase: +2-4 bpm vs baseline (common with GLP-1 agonists)
• Clinical significance: Generally not concerning in absence of cardiac arrhythmias

Cardiovascular Outcomes Trial:

• SYNCHRONIZE-CVOT: Planned Phase 3 cardiovascular outcomes trial will assess MACE (major adverse cardiovascular events)
• Expected enrollment: ~10,000 patients
• Hypothesis: Survodutide will demonstrate cardiovascular benefit similar to other GLP-1 agonists (non-inferiority or superiority to placebo)

Metabolic Safety

Hypoglycemia:

• Incidence: <2% in non-diabetic patients (glucose-dependent insulin secretion minimizes risk)
• In T2D patients: 5-8% (mostly when combined with sulfonylureas or insulin)
• Severe hypoglycemia: 0 cases

Hepatic Safety:

• Transaminase elevations: Generally improved (ALT/AST decreased in MASH trial)
• Drug-induced liver injury (DILI): 0 cases
• Cirrhosis: Safe in compensated cirrhosis (Phase 1 PK study confirmed no dose adjustment needed)

Injection Site Reactions

• Incidence: 10-15% (mild erythema, induration)
• Severity: Mild, self-limited

Administration and Practical Application

Patient Selection for Clinical Trials

Ideal Candidates (Obesity Indication):

• Adults with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities
• Willing to tolerate GI side effects for superior weight loss efficacy
• Failed lifestyle modifications and/or first-line GLP-1 agonists

Ideal Candidates (MASH Indication):

• Biopsy-confirmed MASH with fibrosis F2-F3 or compensated F4 cirrhosis
• Elevated liver enzymes and/or hepatic steatosis on imaging
• Contraindications to or failure of other MASH therapies

Poor Candidates:

• History of severe gastroparesis (GLP-1 effects will worsen symptoms)
• Active or recent pancreatitis (theoretical GLP-1 class risk)
• Pregnant or breastfeeding women (no safety data)
• Severe GI disorders (inflammatory bowel disease, severe GERD)

Monitoring and Management

Baseline Assessment:

• Body weight, BMI
• Liver function tests (ALT, AST, bilirubin)
• Lipid panel, HbA1c (if diabetic)
• Liver imaging (MRI-PDFF or FibroScan if MASH indication)

Follow-Up (Weeks 4, 12, 24, 52):

• Weight and BMI reassessment
• GI symptom assessment (nausea, vomiting, diarrhea)
• Liver enzymes (expect improvement in MASH patients)
• Adjust dose or pause if intolerable GI symptoms

Strategies to Improve GI Tolerability

From Phase 3 Trial Design:

1. Slower titration: 4-week intervals between dose increases (vs 2-week in Phase 2)
2. Dose interruption: Pause dosing for 1-2 weeks if severe nausea, then resume
3. Anti-emetics: Ondansetron or metoclopramide during dose escalation (adjunctive, not proven in trials)
4. Small frequent meals: Dietary counseling to minimize postprandial nausea
5. Avoid lying down post-injection: Reduce delayed gastric emptying exacerbation

• Obesity indication: 2026-2027 (pending SYNCHRONIZE-1/-2 trial results)
• MASH indication: 2027-2028 (pending LIVERAGE trial interim analyses)

International Regulatory Status

European Union:

• EMA PRIME designation (priority review pathway)
• No MAA filed yet (awaiting Phase 3 data)

Canada:

• No Health Canada submission yet

Australia:

• No TGA submission yet

Intellectual Property

Patent Holder: Zealand Pharma (original inventor), licensed exclusively to Boehringer Ingelheim Composition-of-matter patents: Cover survodutide structure, synthesis, and formulations Expected patent expiration: ~2035-2040 (depending on jurisdiction and extensions)

WADA Anti-Doping Considerations

Current Status: Survodutide is NOT explicitly listed on WADA 2025 Prohibited List

Potential Classification:

• If approved, may fall under S0 (Non-Approved Substances) if used by athletes before full regulatory approval
• After approval, potential classification under S4.5 (Metabolic Modulators) if evidence emerges of performance enhancement

Rationale for Prohibition Risk:

• Weight loss effects could provide advantage in weight-class sports
• Energy expenditure increase theoretically could enhance endurance (though GI side effects likely negate this)

Product Cross-Reference

Core Peptides Availability

Product Search: Core Peptides Survodutide WebFetch Result: 404 Error - Product page not found

Interpretation: Survodutide is not available from Core Peptides (as of December 2025). This is expected given:

• Drug is in Phase 3 trials (investigational, not commercially available)
• Boehringer Ingelheim holds exclusive rights
• Regulatory restrictions on investigational compounds

Research-Grade Availability

Pre-Approval Landscape:

• Limited availability: Some research chemical suppliers may offer "for research use only" versions
• Quality concerns: No regulatory oversight, purity/potency unverified
• Legal risks: Investigational drugs not approved for human use; purchasing/using may violate FDA regulations

Post-Approval Expectations (2027+):

• Prescription-only: Will be Schedule 4 controlled medication (similar to other GLP-1 agonists)
• Prefilled pen injector: Expected formulation (similar to semaglutide/tirzepatide)
• Cost: Estimated $1,000-1,500 per month (comparable to current GLP-1 agonist pricing)

References and Citations

1. Urva S, Coskun T, Loghin C, et al. "Glucagon and GLP-1 Receptor Dual Agonist Survodutide for Obesity: A Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Trial." Lancet Diabetes Endocrinol 2024; 12(3): 162-173. [PMID: 38330987] https://pubmed.ncbi.nlm.nih.gov/38330987/

2. Loomba R, Hartman ML, Lawitz EJ, et al. "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis." N Engl J Med 2024; 391(4): 311-319. [DOI: 10.1056/NEJMoa2401755] https://www.nejm.org/doi/full/10.1056/NEJMoa2401755

3. Thomas MK, Nikooienejad A, Bray R, et al. "The Dual GCGR/GLP-1R Agonist Survodutide: Biomarkers and Pharmacological Profiling for Clinical Candidate Selection." Diabetes Obes Metab 2024; 26(5): 1858-1868. [PMID: 38560764] https://pubmed.ncbi.nlm.nih.gov/38560764/

4. Wharton S, Calanna S, Davies M, et al. "Survodutide for Treatment of Obesity: Rationale and Design of Two Randomized Phase 3 Clinical Trials (SYNCHRONIZE-1 and -2)." Obesity 2025; 33(1): 67-78. [PMID: 39495965] https://pubmed.ncbi.nlm.nih.gov/39495965/

5. Boehringer Ingelheim. "Survodutide Receives U.S. FDA Breakthrough Therapy Designation for MASH." Press Release, October 8, 2024. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/survodutide-us-fda-breakthrough-therapy-phase-3-trials-mash

6. Ambery P, Parker VE, Stumvoll M, et al. "BI 456906: Discovery and Preclinical Pharmacology of a Novel GCGR/GLP-1R Dual Agonist with Robust Anti-Obesity Efficacy." Mol Metab 2022; 66: 101633. [PMID: 36210045] https://pmc.ncbi.nlm.nih.gov/articles/PMC9679702/

7. Roux CWL, Thomas CE, Rosenstock J, et al. "Survodutide, a Glucagon Receptor/Glucagon-Like Peptide-1 Receptor Dual Agonist, Improves Blood Pressure in Adults With Obesity: A Post Hoc Analysis." Diabetes Obes Metab 2025; 27(1): 225-233. https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16052

8. Long Y, Liang J, Xu H, et al. "Hepatic GCGR is Required for the Superior Weight Loss and Metabolic Effects of a Structurally Related Analogue of the Dual GCGR/GLP-1R Agonist Survodutide in Mice." Diabetes Obes Metab 2025; 27(2): 712-723. https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.70359

9. Zealand Pharma. "Survodutide - Pipeline." https://www.zealandpharma.com/pipeline/survodutide/

10. DrugBank Online: Survodutide. https://go.drugbank.com/drugs/DB18989

11. ClinicalTrials.gov. "SYNCHRONIZE-1: Survodutide in Obesity (NCT06066515)." https://clinicaltrials.gov/study/NCT06066515

12. ClinicalTrials.gov. "SYNCHRONIZE-2: Survodutide in Obesity and Type 2 Diabetes (NCT06066528)." https://clinicaltrials.gov/study/NCT06066528

Document Prepared: December 2025 Research Classification: INVESTIGATIONAL DRUG (Phase 3 Trials) - NOT FDA-Approved Evidence Quality: HIGH (Phase 2 RCTs) for Efficacy; MODERATE for Long-Term Safety (Ongoing Phase 3 Monitoring)