Survodutide

Survodutide, designated as BI 456906 in development, is a synthetic peptide engineered as a dual agonist targeting both the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R). Structurally, it is a 29-amino-acid peptide derived from the glucagon backbone, featuring a distinctive chemical modification that enhances its pharmacokinetic and pharmacodynamic properties. At position 24, survodutide contains a C18 fatty-diacid side chain conjugated via a hydrophilic glycine-serine spacer, a design that facilitates reversible albumin binding. This albumin interaction extends the peptide's circulation time, enabling once-weekly dosing in clinical contexts. Additionally, a non-coded amino acid, 1-aminocyclobutane-1-carboxylic acid (Ac4c), is incorporated at position 2. This substitution differentiates survodutide from native glucagon and contributes to enhanced receptor selectivity and potency at its dual targets.

Pharmacologically, in vitro studies using CHO-K1 cells demonstrate survodutide's potent activity, with EC50 values of 0.52 nM for GCGR and 0.33 nM for GLP-1R, confirming its strong dual agonist profile. This receptor engagement underpins its investigational utility in metabolic research. The molecular formula of survodutide is C192H289N47O61, with a molecular weight of approximately 4231.7 g/mol. It is registered under CAS number 2805997-46-8 and PubChem CID 168429725, reflecting its well-characterized chemical identity.

The discovery of survodutide originated with Zealand Pharma, who identified its unique dual receptor agonist properties. Subsequently, Boehringer Ingelheim acquired licensing rights and has taken exclusive responsibility for its global development and potential commercialization. At Verified Peptides, we emphasize that survodutide remains an investigational compound available solely for research use. It is not approved by the U.S. Food and Drug Administration (FDA) for any clinical indication.

Importantly, survodutide received FDA Breakthrough Therapy Designation in October 2024 for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) in adults with non-cirrhotic MASH and moderate-to-advanced fibrosis (stages 2-3). This regulatory milestone is significant as it may expedite the drug’s development and review process; however, it is critical to distinguish this designation from FDA approval. Survodutide's investigational status remains unchanged, and it is not authorized for clinical use outside of research settings.

At Verified Peptides, we supply research-grade survodutide for laboratory investigations, supporting studies into its biochemical properties, receptor pharmacology, and potential therapeutic mechanisms. Our material is distinct from the pharmaceutical-grade compound under clinical development and is intended exclusively for experimental research.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

Survodutide (BI 456906) is a synthetic, acylated 29-amino-acid peptide engineered as a dual agonist of the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R). Its design includes a C18 fatty-diacid side chain at position 24, linked via a hydrophilic glycine-serine spacer to facilitate albumin binding, thereby extending its circulation half-life to support once-weekly dosing. Additionally, the incorporation of a non-coded amino acid, 1-aminocyclobutane-1-carboxylic acid (Ac4c), at position 2 enhances receptor selectivity relative to native glucagon. In vitro pharmacology using CHO-K1 cells demonstrates potent dual receptor activity with EC50 values of 0.52 nM at GCGR and 0.33 nM at GLP-1R, confirming its high affinity and balanced agonism.

At Verified Peptides, we recognize that the clinical development of survodutide is led by Boehringer Ingelheim, who licensed the compound from Zealand Pharma and are solely responsible for its global development and commercialization. The investigational drug has received FDA Breakthrough Therapy Designation as of October 2024 for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) in adults with non-cirrhotic disease and moderate-to-advanced fibrosis (stages 2-3). This regulatory milestone signifies an expedited development and review pathway but does not equate to FDA approval, and survodutide remains investigational.

The pivotal phase 3 trial SYNCHRONIZE-1, published in the New England Journal of Medicine (le Roux CW, et al., 2026, DOI 10.1056/NEJMoa2600751), evaluated survodutide in adults with obesity without diabetes. Conducted across 116 sites in 14 countries from November 2023 to February 2026, this double-blind, placebo-controlled study randomized participants 1:1:1 to once-weekly subcutaneous survodutide at dose levels titrated up to 3.6 mg or 6.0 mg, or placebo. Results demonstrated a mean weight loss of up to 16.6% at 76 weeks with survodutide, significantly greater than the 3.2% observed in the placebo group (p<0.0001). Notably, 85.1% of participants receiving survodutide achieved at least 5% weight reduction, while 28.5% of those on the 6.0 mg dose achieved at least 20% weight loss. The trial also reported substantial reductions in adiposity, including up to 34% reduction in visceral fat and up to 63.1% reduction in liver fat relative to baseline, underscoring the compound’s potential impact on obesity-related fat depots.

Complementing these findings, the topline results from the SYNCHRONIZE-MASLD trial, a 48-week study focusing on patients with confirmed liver inflammation or fibrosis, were reported by the sponsoring company. In this trial, 84.2% of survodutide-treated participants achieved at least a 30% relative reduction in liver fat compared to 24.3% of placebo recipients. Furthermore, 61% of those treated with survodutide reached liver-fat normalization, defined as liver fat content below 5%. These data highlight the investigational agent’s potential for modulating hepatic steatosis and inflammation in MASH, aligning with the FDA’s Breakthrough Therapy Designation for this indication.

It is important to emphasize that these clinical trials investigated the pharmaceutical formulation of survodutide developed by Boehringer Ingelheim. At Verified Peptides, we supply research-grade survodutide as a distinct product intended solely for laboratory research use. Our material enables researchers to explore the dual GCGR/GLP-1R agonist mechanism in vitro and in vivo models, independent of clinical development formulations.

Researchers interested in the emerging data on survodutide can access published trial results through PubMed and NIH resources, with SYNCHRONIZE-1 available via the New England Journal of Medicine DOI citation. The evolving clinical landscape and regulatory progress underscore the importance of continued basic and translational research using high-quality peptide reagents to elucidate mechanisms and optimize therapeutic strategies targeting metabolic dysfunction and steatohepatitis.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

At Verified Peptides, we recognize that survodutide (BI 456906) represents a distinct class of dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist peptides, with pharmacological properties that differentiate it from single-receptor GLP-1 agonists commonly studied in obesity and metabolic research. The dual agonism mechanism of survodutide contributes to a unique metabolic profile characterized by pronounced reductions in liver fat and visceral adiposity, effects that exceed what is typically observed with GLP-1 receptor agonism alone. In the SYNCHRONIZE-1 trial, survodutide demonstrated up to a 63.1% reduction in liver fat and a 34% decrease in visceral fat, highlighting its potential utility in research focused on metabolic dysfunction-associated steatohepatitis (MASH) and related conditions where ectopic fat accumulation is a critical factor.

Structurally, survodutide incorporates a non-coded amino acid, 1-aminocyclobutane-1-carboxylic acid (Ac4c), at position 2 of its 29-amino-acid glucagon backbone. This substitution is a significant innovation that enhances receptor selectivity and distinguishes survodutide from native glucagon and other dual agonists. Additionally, the presence of a C18 fatty-diacid side chain at position 24, linked through a hydrophilic glycine-serine spacer, facilitates albumin binding, thereby prolonging systemic circulation and enabling once-weekly dosing regimens in clinical trials. These molecular design features collectively contribute to survodutide’s potent receptor activity, with in vitro EC50 values of 0.52 nM at GCGR and 0.33 nM at GLP-1R, underscoring its high affinity and balanced dual agonism.

From a regulatory perspective, survodutide’s receipt of FDA Breakthrough Therapy Designation in October 2024 for the treatment of adults with non-cirrhotic MASH and moderate-to-advanced fibrosis represents a meaningful milestone in its development pathway. This designation is intended to expedite the clinical development and regulatory review process based on preliminary clinical evidence indicating potential substantial improvement over existing therapies. However, it is critical to emphasize that Breakthrough Therapy Designation is not equivalent to FDA approval; survodutide remains investigational and has not been approved for any indication at this time.

At Verified Peptides, we provide research-grade survodutide suitable for laboratory investigations, enabling the exploration of its dual receptor pharmacology and metabolic effects in preclinical and translational research settings. This availability supports the scientific community in advancing understanding of dual GCGR/GLP-1R agonism and its implications for metabolic disease research.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

At Verified Peptides, we prioritize rigorous quality assurance for our research-grade survodutide to support reliable laboratory investigations. Our survodutide material, a synthetic, acylated 29-amino-acid peptide with a distinctive C18 fatty-diacid side chain and a non-coded amino acid modification, is manufactured to meet stringent purity standards essential for experimental reproducibility. We ensure each batch undergoes comprehensive characterization, including high-performance liquid chromatography (HPLC) to verify purity levels consistently exceeding 95%, thereby minimizing impurities that could confound research outcomes.

In addition to purity assessment, we confirm molecular identity through mass spectrometry, verifying the peptide’s molecular weight of approximately 4231.7 g/mol and the presence of key structural features such as the glycine-serine spacer and 1-aminocyclobutane-1-carboxylic acid (Ac4c) at position 2. This dual analytical approach guarantees the integrity of the survodutide compound supplied for research use.

It is important to emphasize that the survodutide we supply is strictly research-grade and distinct from the pharmaceutical formulation under clinical development by Boehringer Ingelheim. At Verified Peptides, we do not distribute clinical or commercial drug products but focus exclusively on providing high-quality peptides for laboratory research. This distinction ensures that researchers receive material suitable for preclinical and mechanistic studies rather than for therapeutic use.

To support transparency and traceability, each lot of survodutide is accompanied by a third-party certificate of analysis (COA), detailing purity, identity, and quality control results. This documentation facilitates rigorous experimental design and regulatory compliance in academic and industrial research settings.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

At Verified Peptides, we emphasize proper storage and stability practices for research-grade survodutide to maintain its integrity for laboratory use. Survodutide, a synthetic, acylated 29-amino-acid peptide, is typically supplied as a lyophilized powder. For optimal preservation, the lyophilized peptide should be stored at -20°C or colder in a tightly sealed container, protected from moisture and light. This approach minimizes degradation and preserves biological activity over extended periods.

When reconstituting survodutide for experimental use, sterile water or appropriate buffer solutions are recommended, depending on specific assay requirements. It is crucial to avoid repeated freeze-thaw cycles of both lyophilized and reconstituted peptide aliquots, as these can accelerate peptide degradation and reduce potency. Therefore, aliquoting reconstituted peptide into single-use volumes is advisable to maintain consistency across experiments.

The peptide’s albumin-binding C18 fatty-diacid side chain and non-coded amino acid modifications contribute to its stability but do not obviate the need for careful handling. Shelf-life can vary depending on storage conditions, but maintaining low temperatures and minimizing exposure to moisture and repeated thawing cycles are central to preserving peptide quality in research settings. At Verified Peptides, we recommend following these guidelines to ensure reproducible results in preclinical and in vitro studies involving survodutide.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.