Survodutide: what it is, how it works and what studies have found

Survodutide is one of the most advanced glucagon receptor and GLP-1 receptor dual agonists in clinical development. It has finished three phase 3 obesity trials, has a cardiovascular outcomes trial that has completed follow-up, and is in phase 3 for metabolic dysfunction-associated steatohepatitis (MASH). This overview covers its chemistry, its pharmacology, the published trial data and its regulatory position, with every quantitative statement linked to a primary source. It describes published research only and is not medical guidance.

What is survodutide?

Survodutide (development code BI 456906) is a synthetic, acylated peptide that acts as an agonist at two class B G protein-coupled receptors: the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R) [1]. Its design follows the gut hormone oxyntomodulin, which activates both receptors and reduces body weight in humans by lowering energy intake and raising energy expenditure [1].

The developers selected survodutide from 19 dual GCGR/GLP-1R agonists after comparing in vitro potency with in vivo biomarkers of target engagement in mice [2]. It was chosen for a “balanced” profile: glucagon receptor engagement strong enough to add weight-lowering efficacy, with glucose-lowering activity comparable to selective GLP-1 receptor agonism [2].

Survodutide is investigational. Its INN and USAN is survodutide [3], and it is studied in obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), MASH and MASH-related cirrhosis [4][5][6].

Survodutide structure, sequence and molecular weight

Survodutide is built on a glucagon-type backbone of 29 amino acids. Position 2 carries the non-coded residue 1-aminocyclobutane-1-carboxylic acid (Ac4c), introduced for proteolytic stability, and the C-terminus is amidated [1]. Lysine 24 is linked to a short spacer carrying a C18 fatty diacid, the half-life-extending element intended to support once-weekly administration [1][3].

Property	Survodutide
INN / USAN	Survodutide [3]
Development code	BI 456906 [1]
CAS number	2805997-46-8 [7]
Molecular formula	C192H289N47O61 [3][7]
Average molecular weight	About 4,232 g/mol (KEGG: 4231.63; PubChem: 4232) [3][7]
Main-chain length	29 amino acids [1]
Main-chain sequence (one-letter)	H-X-QGTFTSDYSKYLDERAAKDFIKWLESA-NH2, X = Ac4c [3][7]
Side chain	Glu-Gly-Ser-Gly-Ser-Gly-Gly spacer joined to Lys24 by an amide bridge, carrying a C18 fatty diacid [3][1]
Other modifications	Ac4c at position 2; C-terminal amide [1]
Receptors	Glucagon receptor and GLP-1 receptor (agonist) [1]
Salt form	Not defined by the INN; synthetic peptides are usually isolated as acetate or trifluoroacetate salts, which changes the mass per vial

The formula and molecular weight in the table refer to the free peptide. Research material is supplied as a salt, so net peptide content is lower than the gross weight of the powder; a certificate of analysis should state both.

Survodutide mechanism of action

Survodutide activates both target receptors at sub-nanomolar concentrations. In CHO-K1 cells expressing the human receptors, its cAMP EC50 was 0.33 nM at GLP-1R and 0.52 nM at GCGR, roughly tenfold weaker than native GLP-1 (60 pM) and glucagon (20 pM) [1]. Measured in human plasma, the GLP-1R to GCGR potency ratio was about 1:8, which the authors compared with the earlier once-daily dual agonist cotadutide [1]. Evidence level: in vitro.

GLP-1 receptor arm. In mice, survodutide improved glucose tolerance, reduced food intake and slowed gastric emptying, and GLP-1R knockout mice were used to confirm the GLP-1R contribution [1]. A 2026 mouse study found that the glucagon receptor is barely detectable at single-cell level in the area postrema and the arcuate nucleus, whereas GLP-1R is expressed there. Fluorescently labelled survodutide reached circumventricular organs and adjacent nuclei without uniformly crossing the blood-brain barrier, and a long-acting selective GCGR agonist did not activate satiety regions or reduce food intake, supporting a GLP-1R-dependent effect on intake [8]. Evidence level: animal.

Glucagon receptor arm. Glucagon receptor engagement in vivo was shown by increased liver nicotinamide N-methyltransferase (NNMT) mRNA, raised plasma fibroblast growth factor-21 (FGF21) and lower circulating amino acids [1][2]. In diet-induced obese mice survodutide lowered body weight more than maximally effective semaglutide doses, an effect attributed to reduced food intake plus increased energy expenditure [1]. In humans, phase 1 studies recorded lower plasma amino acids and glucagon, read as indirect evidence of engagement at both receptors [9]. Evidence level: animal and phase 1 biomarker.

Survodutide half-life and pharmacokinetics

The developers report mean residence times of 44 hours in mice and 140 hours in dogs, with times to peak concentration of 7 and 51 hours, and considered this profile compatible with once-weekly dosing in humans [1]. The published abstracts of the human phase 1 trials do not state a terminal half-life [9]. In a phase 1 study in people with Child-Pugh A, B or C cirrhosis, single-dose exposure (AUC and Cmax) was similar to that in matched healthy individuals, and the authors concluded that no pharmacokinetic dose adjustment was needed for hepatic impairment [6].

Development history and timeline

Boehringer Ingelheim selected survodutide as its clinical candidate through a structured biomarker programme [2][1]. According to the developer, it was licensed from Zealand Pharma; Boehringer Ingelheim holds global development and commercialisation rights and Zealand Pharma has co-promotion rights in the Nordic countries [10].

Year	Milestone	Ref
2021	Phase 2 obesity trial enrols 387 participants (March to November)	[11]
May 2021	FDA Fast Track designation (MASH)	[10]
2022	Preclinical pharmacology published (as BI 456906)	[1]
2023	Phase 1 single and multiple rising-dose studies published	[9]
Nov 2023	EMA PRIME eligibility for MASH with fibrosis	[10]
Nov 2023	SYNCHRONIZE-1 starts; SYNCHRONIZE-CVOT starts the same month	[12][13]
2024	Phase 2 MASH results published in NEJM	[5]
Sep 2024	FDA Breakthrough Therapy designation, non-cirrhotic MASH with F2 to F3 fibrosis (announced 8 October 2024)	[10]
Oct 2024	Phase 3 LIVERAGE (MASH F2 to F3) starts; LIVERAGE-Cirrhosis announced	[14][10]
Jun 2026	SYNCHRONIZE-1 (NEJM) and SYNCHRONIZE-MASLD (Nature Medicine) published	[4][15]
Oct 2026	SYNCHRONIZE-2 published in NEJM	[16]

Survodutide clinical trials: key studies and findings

Study	Phase / design	Population	n	Duration	Primary endpoint	Main finding	Ref
Phase 1a/1b (NCT03175211, NCT03591718)	1, single and multiple rising doses vs placebo	Healthy men; adults with BMI 27–40	24 + 125	Up to 16 weeks	Safety, PK	Placebo-corrected weight change up to -13.8% at week 16	[9]
NCT04667377	2, dose-finding, double-blind	BMI 27 or more, no diabetes	387	46 weeks	% weight change	-6.2% to -14.9% across four dose arms vs -2.8% placebo	[11]
NCT04153929	2, dose-finding; open-label semaglutide arm	Type 2 diabetes on metformin	413	16 weeks	HbA1c change	HbA1c reduced by up to 1.71 percentage points; weight up to -8.7%	[17]
NCT04771273	2, double-blind	Biopsy-confirmed MASH, F1 to F3	293 treated	48 weeks	MASH improvement, no fibrosis worsening	43% to 62% vs 14% placebo	[5]
NCT05296733	1, open-label	Compensated or decompensated cirrhosis	82	Single dose, then 28 weeks	PK, drug-related AEs	Exposure similar to healthy controls	[6]
SYNCHRONIZE-1 (NCT06066515)	3, double-blind	Obesity without diabetes	725	76 weeks	% weight change; 5% or more loss	-12.2% and -13.0% vs -5.4% placebo	[4]
SYNCHRONIZE-2 (NCT06066528)	3, double-blind	Obesity with type 2 diabetes	752	76 weeks	% weight change; 5% or more loss	-8.2% and -9.8% vs -3.9% placebo	[16]
SYNCHRONIZE-MASLD	3, double-blind, 2:1	Obesity with at-risk MASLD or MASH	216	48 weeks	30% or more liver-fat reduction; % weight change	84.2% vs 24.3% reached the liver-fat threshold (efficacy estimand)	[15]

Phase 2 obesity trial

The phase 2 obesity trial ran at 43 centres in 12 countries and randomised adults with a BMI of 27 kg/m² or more and no diabetes to one of four once-weekly subcutaneous survodutide dose levels or placebo for 46 weeks, comprising 20 weeks of escalation and 26 of maintenance [11]. By planned treatment, mean body-weight change at week 46 ranged from -6.2% in the lowest dose arm to -14.9% in the highest, against -2.8% with placebo [11]. Only 60.4% of the 386 treated participants completed the 46-week treatment period, with similar completion in the survodutide (61%) and placebo (60%) groups [11]. Evidence level: phase 2.

Phase 2 type 2 diabetes trial

In 413 people with type 2 diabetes on metformin, 16 weeks of survodutide lowered HbA1c dose-dependently, by up to 1.71 percentage points from a baseline of 8.07% [17]. A low survodutide dose arm gave an HbA1c reduction similar to open-label semaglutide (-1.46% versus -1.47%), and higher arms gave more weight loss than semaglutide (up to -8.7% versus -5.3%) [17]. Evidence level: phase 2, short duration.

Phase 2 MASH trial

Sanyal and colleagues randomised adults with biopsy-confirmed MASH and fibrosis stage F1 to F3 to three survodutide dose levels or placebo for 48 weeks [5]. Improvement in MASH with no worsening of fibrosis occurred in 47%, 62% and 43% of the three survodutide arms versus 14% with placebo; a decrease in liver fat of at least 30% occurred in 63%, 67% and 57% versus 14%; and fibrosis improved by at least one stage in 34%, 36% and 34% versus 22% [5]. Evidence level: phase 2 with paired biopsies. These data underpinned the FDA Breakthrough Therapy designation and the phase 3 LIVERAGE programme [10].

SYNCHRONIZE-1: obesity without diabetes

SYNCHRONIZE-1 randomised 725 adults with a BMI of 30 kg/m² or more, or 27 kg/m² or more with an obesity-related complication other than diabetes, 1:1:1 to two survodutide maintenance regimens or placebo plus lifestyle counselling [4]. Mean baseline BMI was 37.9 and mean weight 108.8 kg [4]. At week 76, by the treatment-regimen estimand, weight changed by -12.2% and -13.0% with survodutide and -5.4% with placebo; 72.6%, 71.9% and 46.3% lost at least 5% of body weight (P<0.001 for all comparisons with placebo) [4]. The treatment-regimen estimand counts early discontinuation and protocol-prohibited weight-loss drugs, so it is more conservative than an “on-treatment” estimate [4]. A substudy measures body composition and liver fat by MRI [18]. Evidence level: phase 3.

SYNCHRONIZE-2: obesity with type 2 diabetes

SYNCHRONIZE-2 enrolled 752 adults with type 2 diabetes and a BMI of 27 kg/m² or more (mean BMI 36.5, mean age 55.7 years) [16]. At week 76, mean weight change was -8.2% and -9.8% in the two survodutide arms versus -3.9% with placebo, and 57.6%, 64.5% and 35.1% reached at least 5% weight loss [16]. HbA1c fell by 0.9 and 0.8 percentage points with survodutide and 0.2 points with placebo from a baseline of 7.4% [16]. Weight change was smaller than in SYNCHRONIZE-1, which excluded people with diabetes [4][16]. Evidence level: phase 3.

SYNCHRONIZE-MASLD: liver fat

SYNCHRONIZE-MASLD randomised 216 adults with obesity and at-risk MASLD (MASLD with non-invasive or biopsy evidence of inflammation or fibrosis) 2:1 to survodutide or placebo for 48 weeks [15]. At least 30% relative reduction in MRI-PDFF liver fat occurred in 84.2% versus 24.3% by the efficacy estimand and 68.5% versus 28.6% by the treatment-regimen estimand [15]. Mean weight change was -12.2% versus -1.0% (efficacy estimand) and -8.7% versus -1.4% (treatment-regimen estimand) [15]. The authors list the 48-week duration and recruitment limited to the United States and Spain as limitations [15]. Evidence level: phase 3, imaging endpoint.

Ongoing phase 3 programmes

SYNCHRONIZE-CVOT is an event-driven cardiovascular safety trial with a five-point major adverse cardiovascular event (MACE) primary endpoint in adults with a BMI of 27 kg/m² or more and established cardiovascular disease, chronic kidney disease or multiple risk factors [19]. Its registry record lists 5,531 participants and a primary completion date of June 2026; results had not been published at the time of writing [13]. LIVERAGE (MASH with F2 to F3 fibrosis, about 1,800 participants) is recruiting [14], and LIVERAGE-Cirrhosis (compensated MASH cirrhosis, about 1,590 participants) was initiated alongside it in 2024 [10].

Safety findings reported in survodutide studies

The safety profile reported so far is dominated by gastrointestinal events, as with other GLP-1 receptor agonists.

• Phase 2 obesity: adverse events in 91% of survodutide recipients versus 75% with placebo; gastrointestinal events in 75% versus 42% [11].
• Phase 2 MASH: nausea 66% versus 23%, diarrhoea 49% versus 23%, vomiting 41% versus 4%; serious adverse events 8% versus 7% [5].
• SYNCHRONIZE-1: gastrointestinal events, typically mild to moderate, in 80.9% and 89.7% of the survodutide arms versus 47.9% with placebo; no deaths were reported [4].
• SYNCHRONIZE-2: gastrointestinal events in 72.8% and 77.7% versus 38.6% with placebo, generally mild to moderate and transient [16].
• Phase 1: in the multiple rising-dose study, 12.5% of Part A participants discontinued, most commonly because of a cardiac or vascular adverse event (7.5%); in Part B, 17.8% discontinued, mainly because of adverse events (13.3%), most commonly gastrointestinal disorders [9].

Long-term cardiovascular safety will be defined by SYNCHRONIZE-CVOT [19].

Regulatory status of survodutide by region

Region	Status (October 2026)	Ref
United States	Investigational; Fast Track (2021) and Breakthrough Therapy (2024) designations for non-cirrhotic MASH with F2 to F3 fibrosis; not approved	[10][16]
European Union	Investigational; PRIME eligibility (2023) for MASH with fibrosis; not authorised	[10]
United Kingdom	Investigational; no marketing authorisation identified	[16]
China	Investigational; not approved	[16]
Japan	Investigational; not approved	[16]
India	Investigational; no marketing authorisation identified	[16]

The SYNCHRONIZE-2 paper of October 2026 still describes survodutide as investigational [16]. Breakthrough Therapy and PRIME status speed development and regulatory interaction but do not establish efficacy or safety for any use.

Survodutide in laboratory research

Published preclinical work gives a practical template for in vitro and animal studies of the molecule.

• Receptor potency. cAMP accumulation in CHO-K1 cells stably expressing human GCGR or GLP-1R, with and without human plasma to account for albumin binding [1][2]. Endogenous-receptor assays used MIN6 insulinoma cells (mouse GLP-1R) and rat primary hepatocytes (GCGR) [2].
• Target-engagement biomarkers. Oral glucose tolerance for GLP-1R; liver NNMT mRNA, plasma FGF21 and amino acids for GCGR [2][1].
• Models. Diet-induced obese mice for body weight and energy expenditure, db/db mice for glycaemia, GLP-1R knockout and reporter mice for receptor attribution, and fluorophore-labelled peptide with c-Fos mapping for central sites of action [1][2][8].
• Analytical identity and quantitation. A 2026 multiplexed LC-HRMS method separates and identifies survodutide alongside eight other GLP-1-based peptides, including tirzepatide and mazdutide, on a C18 column with accurate-mass full scan plus data-dependent MS/MS, with mass accuracy of 0.0 to 0.5 ppm [20].

For research material, identity is normally confirmed by LC-MS intact mass and peptide mapping, and purity by reversed-phase HPLC or UPLC. The C18 diacid makes the molecule strongly retained on reversed-phase columns; the LC-HRMS method above used a C18 column at 50 °C with difluoroacetic acid and dimethyl sulfoxide as mobile-phase additives [20].

Synthesis, purity and impurities

Survodutide is made by chemical synthesis, normally Fmoc solid-phase peptide synthesis (SPPS), with the spacer and fatty diacid built onto lysine 24 through an orthogonally protected lysine. Our guide to SPPS versus LPPS explains the route choices for long acylated peptides.

The impurity classes to watch follow from the structure: deletion and insertion sequences from incomplete couplings along the 29-residue chain, racemised (D-amino acid) variants, deamidation of Gln3, oxidation of Trp25, incomplete or misplaced acylation, and truncated spacer variants. Purity specifications and impurity thresholds for synthetic peptides are covered in peptide API impurities and specifications. Impurity profile matters even for in vitro work, because closely related variants can carry different receptor potencies and skew EC50 estimates.

Storage and stability of lyophilized survodutide

Survodutide research material is supplied as a lyophilized (freeze-dried) powder. Typical laboratory practice is storage at -20 °C or below, protected from light and moisture, with the container brought to room temperature before opening to avoid condensation. Acylated peptides can adsorb to plastic and glass surfaces in dilute solution, so assay buffers often include a carrier such as albumin; this also matches the plasma-shift conditions used in published potency assays [1]. General principles are in lyophilised peptide stability and storage.

Survodutide vs tirzepatide

Survodutide and tirzepatide are both once-weekly, fatty-acid-acylated peptides that activate the GLP-1 receptor, but they pair it with different second receptors: the glucagon receptor for survodutide and the GIP receptor for tirzepatide [1][21]. Tirzepatide was approved by the FDA for chronic weight management in November 2023 [21]; survodutide is investigational [16].

Feature	Survodutide	Tirzepatide
Receptors	GCGR + GLP-1R [1]	GIPR + GLP-1R [21]
Main-chain length	29 amino acids [1]	39 amino acids [22]
Molecular formula	C192H289N47O61 [3]	C225H348N48O68 [22]
Status	Investigational [16]	FDA-approved for chronic weight management (2023) [21]
Phase 3, obesity without diabetes	SYNCHRONIZE-1, 76 weeks: -13.0% (higher arm) vs -5.4% placebo [4]	SURMOUNT-1, 72 weeks: -20.9% (highest arm) vs -3.1% placebo [23]
Phase 3, obesity with type 2 diabetes	SYNCHRONIZE-2, 76 weeks: -9.8% vs -3.9% [16]	SURMOUNT-2, 72 weeks: -14.7% vs -3.2% [24]
Phase 2, MASH	Improvement in MASH without fibrosis worsening: up to 62% vs 14% [5]	Resolution of MASH without fibrosis worsening: up to 62% vs 10% [25]

All figures in the table come from separate trials, and none of these is a head-to-head comparison. SYNCHRONIZE-1 and SURMOUNT-1 both used treatment-regimen estimands, but they differ in duration, dose-escalation schemes, populations and placebo responses (-5.4% versus -3.1%) [4][23]. The MASH trials used different histological endpoints (“improvement” versus “resolution” of MASH), so their percentages are not comparable [5][25]. The scientific question that separates the two molecules is whether glucagon receptor agonism brings added liver-fat and energy-expenditure effects; the MASLD and LIVERAGE programmes are designed to test the liver side of that question [15][14]. Tirzepatide’s structure and supply are covered on our tirzepatide page, and the other glucagon/GLP-1 dual agonist in late development is reviewed in mazdutide: structure, mechanism and research findings.

How Winhycare Pharma supplies survodutide

Winhycare Pharma supplies survodutide as research-use-only material to research organisations and laboratories, at a purity of 99% or higher as stated in our product brochure, with a certificate of analysis covering HPLC purity and mass confirmation. Custom synthesis of survodutide analogues, labelled variants and fragments is available. Product details are on the survodutide research peptide page, and enquiries go through our research peptide contact form.

For laboratory research use only. Not for human or veterinary use.