Survodutide (BI 456906): what the phase 3 trials found, how it compares with tirzepatide and retatrutide, and what 'survodutide peptide' vials are
What 91 indexed publications and 10 randomized trials actually state about survodutide, sentence by sentence, each tied to its source and labeled by the kind of evidence it is.
At a glance
What survodutide is, and where its trials stand
Survodutide is a peptide in the incretin & amylin analogs class (glucagon and GLP-1 receptor dual agonist). Europe PMC indexes 91 publications naming it or a listed alias in a title or abstract, including 10 randomized controlled trials and 15 clinical trials of any design, as of . The strongest evidence tier in that literature is human clinical trials.
This page reports what those studies state, sentence by sentence, with each statement tied to its source and labeled by the kind of evidence it is. It does not recommend use, and it does not translate study doses into anything personal.
What the evidence level means
Publication counts show what is indexed, not how strong the evidence is. The ledger below separates human clinical records from preclinical, analytical, and in-vitro work.
Interpretation boundary: An indexed publication count is a discovery measure. It does not establish efficacy, safety, approval, or a personal treatment plan.
Survodutide in two minutes
What it is. A once-weekly injectable peptide that activates both the glucagon and GLP-1 receptors, designed by Zealand Pharma and developed by Boehringer Ingelheim for obesity, type 2 diabetes and metabolic liver disease.
What the research actually shows. 91 indexed publications and a phase 1 to phase 3 programme. In SYNCHRONIZE-1 (725 adults with obesity, 76 weeks) weight fell 12.2% on 3.6 mg and 13.0% on 6.0 mg against 5.4% on placebo. In SYNCHRONIZE-MASLD (216 adults with obesity and at-risk liver disease) 84% on 6.0 mg cut liver fat by at least 30%, against 24% on placebo. In type 2 diabetes it lowered HbA1c by up to 1.7 points at 16 weeks and improved beta-cell function. Nausea and diarrhoea lead the side effects and fall with slower titration.
Where it stands. Not approved anywhere yet. A 4,935-person cardiovascular outcomes trial is enrolling. The type 2 diabetes phase 3 has not published results.
How it compares. Its 76-week weight loss sits below the published figures for tirzepatide and retatrutide and near semaglutide's; its liver-fat result is its distinctive claim. No trial has compared it head-to-head with any of them.
What 'survodutide peptide' vials are. Unregulated copies of an investigational drug, sold before any regulator has reviewed it, with no way for a buyer to verify the contents.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
How survodutide works: glucagon plus GLP-1 in one molecule
Written from general pharmacology and the development record, and marked as editorial synthesis; the measurements behind it are quoted in the biomarker section.
- Editorial synthesis from general knowledge
- Editorial synthesis from general knowledge
- Editorial synthesis from general knowledge
What happened in the human studies?
This record's ledger holds 12 primary human studies, of which 9 are trials. Few enough to show in full: each card quotes what its abstract reported about Survodutide. Read them before any other section on this page.
-
At week 76, the mean change in body weight from baseline according to the treatment-regimen estimand was -12.2% (95% confidence interval [CI], -13.6 to -10.8) in the 3.6-mg group, -13.0% (95% CI, -14.4 to -11.6) in the 6.0-mg group, and -5.4% (95% CI, -6.9 to -4.0) in the placebo group; 72.6%, 71.9% and 46.3% of the participants, respectively, had weight reduction of at least 5% (P Conclusions Survodutide led to significantly greater reductions in body weight than placebo in adults with obesity without diabetes.
Sourcepmid-42253238· quoted verbatim from the abstract -
Survodutide was associated with significant decreases in HOMA-IR, glucagon, C-peptide, fasting insulin, and FPG versus placebo, and significant increases in HMW adiponectin.
Sourcepmid-42331726· quoted verbatim from the abstract -
In total, 84.2% of survodutide-treated patients versus 24.3% of placebo-treated patients had ≥30% reduction in LFC using the efficacy estimand (P < 0.0001; treatment regimen estimand: 68.5% versus 28.6%, respectively; P < 0.0001).
Sourcepmid-42252333· quoted verbatim from the abstract -
Recommendations from the CTS led to changes in visit interval, increased virtual visit options, and changes in participant materials.
Sourcepmid-41704810· quoted verbatim from the abstract -
SYNCHRONIZE-2 will determine the efficacy, safety and tolerability of survodutide for BW reduction in people with obesity and T2D, whose baseline characteristics suggest a representative, diverse cohort.
Sourcepmid-41216778· quoted verbatim from the abstract -
Mean haemoglobin A1c was 5.5%, estimated glomerular filtration rate 93.0 mL/min/1.73 m 2 , systolic/diastolic blood pressure 127.0/82.7 mmHg, and low-density lipoprotein cholesterol 116.4 mg/dL; 21.8% were taking lipid-lowering drugs.
Sourcepmid-41187967· quoted verbatim from the abstract -
After 46 weeks of survodutide treatment, females had greater reductions in bodyweight and waist circumference than males.
Sourcepmid-39821928· quoted verbatim from the abstract -
The mean reduction in HbA 1c was similar with low-dose survodutide (DG2: -15.95 mmol/mol [-1.46%]; n=46) and semaglutide (-16.07 mmol/mol [-1.47%]; n=45).
Sourcepmid-38095657· quoted verbatim from the abstract -
BI 456906 reduced plasma amino acids and glucagon, indicating target engagement at GCGRs and GLP-1Rs.
Sourcepmid-36527386· quoted verbatim from the abstract -
The primary endpoints are percentage change in body weight and achievement of body weight reduction ≥ 5% from baseline to Week 76.
Sourcepmid-42219222· quoted verbatim from the abstract -
The primary endpoints are percentage change in body weight and proportion of participants achieving ≥5% body weight reduction from baseline to week 76.
Sourcepmid-39495965· quoted verbatim from the abstract -
SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk.
Sourcepmid-39453356· quoted verbatim from the abstract
Trial by trial: what survodutide did in people
Every human study in the ledger with results, then the phase 3 trials that have published only their design.
| Trial | Participants | Dose and duration | Primary result | Adverse events |
|---|---|---|---|---|
| SYNCHRONIZE-1 (le Roux 2026, NEJM) | 725 adults with obesity, no diabetes; mean BMI 37.9 | Weekly SC, titrated to 3.6 or 6.0 mg; 76 weeks | -12.2% and -13.0% vs -5.4% placebo | Full tables in the paper; abstract gives efficacy |
| SYNCHRONIZE-MASLD (Kaplan 2026, Nature Medicine) | 216 adults with obesity and at-risk MASLD or biopsy-confirmed MASH | Weekly SC 6.0 mg vs placebo, 2:1 | 84.2% vs 24.3% achieved a 30% liver-fat reduction; weight also fell | Most frequent events gastrointestinal (from the abstract) |
| Phase 2 obesity (le Roux 2025 subgroup paper) | 387 adults with BMI 27 or more | Weekly SC, several doses; 46 weeks | Clinically meaningful weight and waist reductions at all doses; larger in women and at lower baseline BMI | Nausea the most frequent GI event in every subgroup |
| Phase 2 type 2 diabetes (Blüher 2024) | 413 adults on metformin; open-label semaglutide arm | 0.3 to 2.7 mg weekly or 1.2 to 1.8 mg twice weekly; 16 weeks | HbA1c down 0.9 to 1.7 points; weight down | Dose-related GI events, reduced by slower titration |
| Beta-cell analysis (Ekinci 2026) | Participants of both phase 2 trials | As above | HOMA-β up rapidly in diabetes; insulin resistance, glucagon and fasting glucose down in both | — |
| Phase 1 (Jungnik 2023) | 24 in single-dose; multiple-dose parts | Single rising doses; multiple doses over 16 weeks | Placebo-corrected weight loss 13.8% at week 16 on the top schedule | Drug-related events rose with dose; decreased appetite in 50% at single doses |
| Meta-analysis (Awad 2025) | Four randomized trials to May 2024 | Pooled | Weight and HbA1c reduced | Overall events comparable with placebo; diarrhoea 1.9 times as likely |
| Trial | Population | Size | Status in the ledger |
|---|---|---|---|
| SYNCHRONIZE-2 | Obesity with type 2 diabetes, 19 countries | 752 treated | Baseline characteristics published; results not yet |
| SYNCHRONIZE-JP | Japanese adults with obesity disease | 274 | Design and baseline published |
| SYNCHRONIZE-CVOT | Obesity with cardiovascular or kidney disease | 4,935 target | Event-driven cardiovascular safety trial; enrolling |
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
What the evidence shows
One row per primary study in this record's ledger. Fields are read from each paper's indexing and abstract. "Analytical method" marks papers about detecting or measuring the compound rather than about its effects.
| Study | Design | n | Species | Dose | Route | Duration | Reported outcome | Tier |
|---|---|---|---|---|---|---|---|---|
| le 2026 | Randomized controlled trial | 725 | Humans | 3.6 mg | subcutaneous | — | At week 76, the mean change in body weight from baseline according to the treatment-regimen estimand was -12.2% (95% confidence interval [CI], -13.6 to -10.8) in the 3.6-mg group, -13.0% (95% CI, -14.4 to -11.6) in the… | Human clinical trial |
| Ekinci 2026 | Randomized controlled trial | 413 | Humans | — | — | 16 weeks; 46 weeks | Survodutide was associated with significant decreases in HOMA-IR, glucagon, C-peptide, fasting insulin, and FPG versus placebo, and significant increases in HMW adiponectin. | Human clinical trial |
| Kaplan 2026 | Randomized controlled trial | 146 | Humans | 6.0 mg | subcutaneous | — | In total, 84.2% of survodutide-treated patients versus 24.3% of placebo-treated patients had ≥30% reduction in LFC using the efficacy estimand (P < 0.0001; treatment regimen estimand: 68.5% versus 28.6%, respectively;… | Human clinical trial |
| Rubino 2026 | Clinical trial | — | Humans | — | — | — | Recommendations from the CTS led to changes in visit interval, increased virtual visit options, and changes in participant materials. | Human clinical trial |
| Wharton 2026 | Randomized controlled trial | — | Humans | — | subcutaneous | — | SYNCHRONIZE-2 will determine the efficacy, safety and tolerability of survodutide for BW reduction in people with obesity and T2D, whose baseline characteristics suggest a representative, diverse cohort. | Human clinical trial |
| le 2026 | Randomized controlled trial | 725 | Humans | — | subcutaneous | — | Mean haemoglobin A1c was 5.5%, estimated glomerular filtration rate 93.0 mL/min/1.73 m 2 , systolic/diastolic blood pressure 127.0/82.7 mmHg, and low-density lipoprotein cholesterol 116.4 mg/dL; 21.8% were taking… | Human clinical trial |
| le 2025 | Randomized controlled trial | 387 | Humans | — | subcutaneous | 46 weeks | After 46 weeks of survodutide treatment, females had greater reductions in bodyweight and waist circumference than males. | Human clinical trial |
| Blüher 2024 | Randomized controlled trial | 50 | Humans | 1.8 mg | subcutaneous | 75 years; 16 weeks | The mean reduction in HbA 1c was similar with low-dose survodutide (DG2: -15.95 mmol/mol [-1.46%]; n=46) and semaglutide (-16.07 mmol/mol [-1.47%]; n=45). | Human clinical trial |
| Jungnik 2023 | Phase 1 clinical trial | 24 | Humans | — | subcutaneous | — | BI 456906 reduced plasma amino acids and glucagon, indicating target engagement at GCGRs and GLP-1Rs. | Human clinical trial |
| Yokote 2026 | Human study | — | Humans | — | — | — | The primary endpoints are percentage change in body weight and achievement of body weight reduction ≥ 5% from baseline to Week 76. | Observational, human |
| Wharton 2025 | Human study | 726 | Humans | — | subcutaneous | — | The primary endpoints are percentage change in body weight and proportion of participants achieving ≥5% body weight reduction from baseline to week 76. | Observational, human |
| Kosiborod 2024 | Human study | 935 | Humans | — | subcutaneous | — | SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk. | Observational, human |
| Zimmermann 2026 | Animal study | — | Mice | — | — | — | Consistent with the hypothesis that the intake suppressive effects of survodutide are GLP-1R dependent, a long-acting GCGR agonist did not induce neuronal activation in satiety-mediating regions, nor reduced food… | Animal, preclinical |
| Doiron 2025 | Animal study | — | Rats, Mice | — | — | — | Cystathionine-γ-lyase knockout worsened HFpEF, whereas pharmacological supplementation with an H 2 S donor improved diastolic function and reduced cardiac fibrosis. | Animal, preclinical |
| Augustin 2025 | Animal study | — | Mice | — | — | — | Significant bodyweight reductions were not observed with BI 1820237 alone in diet-induced obese mice, however combination with survodutide led to bodyweight reduction of 22% which was significantly (p Conclusion… | Animal, preclinical |
| Thomas 2024 | Animal study | — | Rats, Mice | — | — | — | Upon acute dosing in lean mice, target engagement biomarkers for the GCGR and GLP-1R demonstrated a significant correlation (Spearman correlation coefficient with p Conclusions Survodutide was selected as the clinical… | Animal, preclinical |
| Zimmermann 2022 | Animal study | — | Mice | — | — | — | Pharmacological doses of BI 456906 provided greater bodyweight reductions in mice compared with maximally effective doses of the GLP-1R agonist semaglutide. | Animal, preclinical |
Doses reported in studies
Each entry is a sentence quoted from the study's abstract, with the study's design, sample size and year in front of it. Comparator doses in the same sentence are not attributed to survodutide.
- Source
pmid-42253238 - Source
pmid-42252333 - Source
pmid-38095657 - Source
pmid-39495965
Every survodutide dose in the trials, in one table
Every figure here is a trial dose with medical supervision and titration. The drug is not sold by any pharmacy.
| Trial phase | Route | Dose | Schedule | Population |
|---|---|---|---|---|
| Phase 3 (SYNCHRONIZE-1, -2, -JP) | Subcutaneous | Titrated up to 3.6 mg or 6.0 mg; flexibility permitted | Once weekly, 76 weeks | Obesity with and without type 2 diabetes |
| Phase 3 (SYNCHRONIZE-MASLD) | Subcutaneous | 6.0 mg | Once weekly | Obesity with at-risk liver disease |
| Phase 2 obesity | Subcutaneous | Several doses (0.6 to 4.8 mg in the published design) | Once weekly, 46 weeks | BMI 27 or more |
| Phase 2 type 2 diabetes | Subcutaneous | 0.3, 0.9, 1.8, 2.7 mg weekly; 1.2 or 1.8 mg twice weekly | 16 weeks with titration | Type 2 diabetes on metformin |
| Phase 1 | Subcutaneous | Single rising doses; multiple-dose schedules | Up to 16 weeks | Healthy and overweight volunteers |
The titration is the point of the table: every phase 3 participant reached 3.6 or 6.0 mg over weeks, and the phase 2 diabetes trial showed the gastrointestinal effects depend on how fast that climb is. A vial sold as 'survodutide peptide' comes with neither the titration nor the supervision, and its content is unverified. Nothing on this page is an instruction to take anything.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Side effects: what the trials recorded, and what is still being measured
From placebo-controlled trials with hundreds of participants: gastrointestinal events lead, are dose-related and are reduced by slower titration. The cardiovascular outcomes trial has not reported. Events and their frequency as each study reported them, with the denominator where the abstract gives one.
- Source
pmid-38095657 - Source
pmid-36527386 - Source
pmid-39821928 - Source
pmid-40557198 - Editorial synthesis from general knowledge
Who survodutide is discussed for, and the cautions that recur
Studied: adults with a BMI of 30 or more, or 27 with a complication, with and without type 2 diabetes; adults with obesity and at-risk metabolic liver disease; healthy volunteers in phase 1. Being studied: adults with obesity and cardiovascular or kidney disease, in the outcomes trial. Community: people buying gray-market vials as an alternative to the approved GLP-1 drugs.
The cautions follow from the class and from what the programme has not yet measured:
- Gastrointestinal effects. Nausea and diarrhoea are dose-related and titration-dependent; the trials titrated over weeks under supervision.
- The glucagon component. Glucagon raises heart rate and glucose and increases energy expenditure; the GLP-1 half offsets the glucose effect in the trials. Cardiovascular outcomes are unmeasured until SYNCHRONIZE-CVOT reports.
- Class warnings. GLP-1 receptor agonists carry warnings on pancreatitis, gallbladder disease, thyroid C-cell tumours in rodents and, for people with diabetes, retinopathy progression; nothing specific to survodutide is documented in the ledger, and nothing rules it out.
- Lean mass. Rapid weight loss on any agent in this class includes muscle and bone; a 2024 review in the ledger addresses it for the class.
- Gray-market vials. No reference standard, no pharmacy, no titration guidance and no way to verify contents. The trial data describe a drug, not a vial.
- Pregnancy and children. Excluded from every trial.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Biomarkers measured in studies
Laboratory and clinical measures the studies report tracking, including which hormones did and did not change.
-
In this phase 3, double-blind trial, we randomly assigned adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes), in a 1:1:1 ratio to receive once-weekly survodutide administered subcutaneously at a dose adjusted up to 3.6 mg or 6.0 mg or placebo, in addition to counseling for lifestyle modification.
Sourcepmid-42253238· quoted verbatim from the abstract -
This post hoc analysis evaluated the effect of survodutide on beta-cell function, insulin sensitivity, and glucose biomarkers in two phase 2 trial populations.
Sourcepmid-42331726· quoted verbatim from the abstract -
Mean percentage change in body weight was -12.2% with survodutide and -1.0% with placebo using the efficacy estimand (P < 0.0001; treatment regimen estimand: -8.7% versus -1.4%, respectively; P < 0.0001).
Sourcepmid-42252333· quoted verbatim from the abstract -
Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m 2 and T2D were randomized 1:1:1 to weekly subcutaneous survodutide (up-titrated to 3.6 or 6.0 mg) or placebo with recommendations for modified diet and physical activity.
Sourcepmid-41216778· quoted verbatim from the abstract -
Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m 2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 or 6.0 mg) or placebo for 76 weeks.
Sourcepmid-41187967· quoted verbatim from the abstract -
To explore the effects of sex and baseline body mass index (BMI) on the efficacy and safety of survodutide in people with a BMI ≥27 kg/m 2 .
Sourcepmid-39821928· quoted verbatim from the abstract
Reported interactions
Sentences in which the compound is studied alongside another agent. Read the quotation: the word interaction can also be statistical.
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We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy alone and in combination with the glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist survodutide.
Sourcepmid-40619099· quoted verbatim from the abstract
Reported timelines
Onset, peak and duration figures as each study reported them.
- Source
pmid-42253238 - Source
pmid-36527386 - Source
pmid-36356832 - Source
pmid-42331726
What is measured over time, and what is not
Survodutide's time course is well mapped for an unapproved drug. Weeks: appetite falls with the first doses and gastrointestinal effects peak during titration. 16 weeks: HbA1c down up to 1.7 points in diabetes; 13.8% placebo-corrected weight loss on the top phase 1 schedule. 46 weeks: the phase 2 obesity result. 76 weeks: 12 to 13% weight loss in SYNCHRONIZE-1. What is not measured is what happens after stopping, whether the beta-cell improvements persist off treatment, and, above all, hard cardiovascular outcomes, which the enrolling outcomes trial exists to measure. 'How long does it take to work' has a trial answer of weeks for appetite and a year and a half for the full effect.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Escalation schedules used in studies
How trials stepped doses, reported as study design.
-
The most frequently reported adverse events with survodutide were gastrointestinal, commonly occurring during dose escalation, and were generally of mild-to-moderate severity.
Sourcepmid-42252333· quoted verbatim from the abstract -
Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m 2 and T2D were randomized 1:1:1 to weekly subcutaneous survodutide (up-titrated to 3.6 or 6.0 mg) or placebo with recommendations for modified diet and physical activity.
Sourcepmid-41216778· quoted verbatim from the abstract -
Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m 2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 or 6.0 mg) or placebo for 76 weeks.
Sourcepmid-41187967· quoted verbatim from the abstract -
Totally 387 people (aged 18-75 years, BMI ≥27 kg/m 2 , without diabetes) were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6 or 4.8 mg) or placebo for 46 weeks (20-week dose escalation; 26-week dose maintenance).
Sourcepmid-39821928· quoted verbatim from the abstract -
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m 2 .
Sourcepmid-36527386· quoted verbatim from the abstract
Study durations
Treatment and follow-up periods as stated in each abstract.
- Durations stated: 16 weeks; 46 weeks
Trial 1404-0002 randomised 413 participants with type 2 diabetes on metformin to receive survodutide, placebo, or semaglutide over 16 weeks.
Sourcepmid-42331726· quoted verbatim from the abstract, emphasis added - Durations stated: 46 weeks
After 46 weeks of survodutide treatment, females had greater reductions in bodyweight and waist circumference than males.
Sourcepmid-39821928· quoted verbatim from the abstract, emphasis added - Durations stated: 75 years; 16 weeks
This Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, conducted in clinical research centres, assessed survodutide in participants aged 18-75 years with type 2 diabetes, an HbA 1c level of 53-86 mmol/mol (7.0-10.0%) and a BMI of 25-50 kg/m 2 on a background of metformin therapy.
Sourcepmid-38095657· quoted verbatim from the abstract, emphasis added
Routes: once-weekly subcutaneous injection in every trial
Subcutaneous once a week in every human trial, titrated over weeks. Nothing else has been studied in people. Routes of administration named in each study.
- administration by subcutaneous route reported
In this phase 3, double-blind trial, we randomly assigned adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes), in a 1:1:1 ratio to receive once-weekly survodutide administered subcutaneously at a dose adjusted up to 3.6 mg or 6.0 mg or placebo, in addition to counseling for lifestyle modification.
Sourcepmid-42253238· quoted verbatim from the abstract - administration by subcutaneous route reported
Participants were randomized (2:1) and treated with once-weekly subcutaneous injections of survodutide 6.0 mg (n = 146) or placebo (n = 70).
Sourcepmid-42252333· quoted verbatim from the abstract - administration by subcutaneous route reported
Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m 2 and T2D were randomized 1:1:1 to weekly subcutaneous survodutide (up-titrated to 3.6 or 6.0 mg) or placebo with recommendations for modified diet and physical activity.
Sourcepmid-41216778· quoted verbatim from the abstract - administration by subcutaneous route reported
Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m 2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 or 6.0 mg) or placebo for 76 weeks.
Sourcepmid-41187967· quoted verbatim from the abstract - administration by subcutaneous route reported
Totally 387 people (aged 18-75 years, BMI ≥27 kg/m 2 , without diabetes) were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6 or 4.8 mg) or placebo for 46 weeks (20-week dose escalation; 26-week dose maintenance).
Sourcepmid-39821928· quoted verbatim from the abstract - administration by subcutaneous route reported
Aims/hypothesis The aim of this study was to assess the dose-response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide (BI 456906) on HbA 1c levels and bodyweight reduction.
Sourcepmid-38095657· quoted verbatim from the abstract
What people report outside the literature
Forum reports are experiences with grey-market vials of an investigational drug. The trial results are public; the vials' contents are not. What circulates in user communities and clinic marketing, reported so a reader knows the figures and their origin. None of it has been tested in a trial, and none of it is a suggestion.
- Editorial synthesis from general knowledge
Reconstitution mathematics
Lyophilised peptide is supplied as a mass in a vial and dissolved in a stated volume of diluent. Two figures follow from that and nothing else:
- Concentration = mass in vial ÷ diluent volume. A 5 mg vial in 2 mL is 2.5 mg/mL, or 2,500 mcg/mL.
- Volume for a given mass = that mass ÷ concentration. 250 mcg at 2,500 mcg/mL is 0.1 mL. On a U-100 insulin syringe, where 1 mL is 100 units, that is 10 units.
Study doses on this page are quoted as published, in the units the authors used. Converting between mcg, mg and IU, or between a mass and a syringe volume, is arithmetic; deciding a mass is not, and this page does not do it. The reconstitution calculator performs the conversion with the formula shown.
Reading a certificate of analysis
A certificate of analysis is a laboratory report on one batch. Reading it means checking four things in order.
- Identity. Mass spectrometry should report an observed molecular mass matching the peptide's theoretical mass within the instrument's stated tolerance. A certificate with no mass spectrometry, or one that lists only the expected value, has not confirmed identity.
- Purity. HPLC purity is the area of the main peak as a share of all peaks, at a stated wavelength. It says nothing about what the other peaks are, and it is not a measure of quantity.
- Quantity. Net peptide content, by amino acid analysis or UV, is the fraction of the vial's mass that is peptide rather than counter-ions and water. A 5 mg vial at 80% net content holds 4 mg of peptide, and every concentration figure above changes accordingly.
- Provenance. The batch number on the certificate should match the vial, the laboratory should be named and independent of the seller, and the test date should be recent.
This page rates no supplier and links to none. It describes how to read the document.
Equipment described in studies
Published human studies of injectable peptides report the same small set of materials: single-use insulin syringes with fixed needles, most often U-100 with 29 to 31 gauge needles; bacteriostatic water or sterile water for injection as diluent, with the choice stated in the methods; alcohol swabs; and refrigerated storage of reconstituted solution. Animal studies more often report intraperitoneal or intragastric administration and state the vehicle used. Where a study in this record's ledger names its materials or vehicle, that sentence appears under storage or routes above; where it does not, nothing is assumed here.
Storage and handling
Trial product was supplied by the sponsor as a solution for weekly injection under its own handling instructions, which are not public. Gray-market vials are lyophilised powders of unverified content; nothing about their stability has been published, and the drug's albumin-binding side chain makes it sensitive to how it is reconstituted.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Common mistakes in how survodutide is discussed
- Ranking it against tirzepatide and retatrutide on trial percentages. Different trials, populations, durations and estimands. No head-to-head trial exists.
- Calling it approved, or 'coming soon' with a date. Phase 3 is complete in two indications; no regulator has decided, and the ledger holds no filing document.
- Treating a vial as the drug. The trial data belong to a sponsor-manufactured product given with titration and supervision. A 'survodutide peptide' vial is a claim on a label.
- Missing what is different about it. The glucagon receptor is the reason for the liver-fat result and for the cardiovascular question. A page that treats it as another GLP-1 drug misses both.
- Quoting the phase 1 13.8% as the headline. That was placebo-corrected at 16 weeks in a small study; the phase 3 figure is 12 to 13% at 76 weeks against 5% on placebo.
- Assuming the diabetes phase 3 has reported. Only its baseline paper is out.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Survodutide vs tirzepatide, semaglutide, retatrutide and mazdutide
| Agent | Receptors | Weight loss in its pivotal trial | Status |
|---|---|---|---|
| Survodutide | Glucagon + GLP-1 | 12.2 to 13.0% vs 5.4% placebo at 76 weeks (SYNCHRONIZE-1) | Phase 3 complete in obesity and MASLD; not approved |
| Tirzepatide | GIP + GLP-1; 2756 indexed publications, 131 randomized trials | About 15 to 21% at 72 weeks (SURMOUNT-1) | Approved 2022 |
| Semaglutide | GLP-1; 6039 indexed publications, 305 randomized trials | About 15% at 68 weeks (STEP 1) | Approved 2017 |
| Retatrutide | Glucagon + GIP + GLP-1; 197 indexed publications, 7 randomized trials | About 24% at 48 weeks in phase 2; phase 3 ongoing | Not approved |
| Mazdutide | Glucagon + GLP-1 (the closest analogue) | About 15% at 48 weeks in its Chinese phase 3 | Approved in China (2025); no record on this site |
| Cagrilintide (with semaglutide as CagriSema) | Amylin + GLP-1; 105 indexed publications | About 20% at 68 weeks in REDEFINE-1 | Not approved; see the CagriSema record |
Two comparisons are worth more than the percentages. Mazdutide is the same receptor pair and is approved in China, so it is the nearest evidence for what a glucagon-GLP-1 dual agonist does at scale. Retatrutide adds a third receptor and posts larger phase 2 numbers over shorter periods. Against the approved drugs, survodutide's liver-fat result is its distinctive claim and its cardiovascular data its missing piece. No trial has compared it with any of them, and the site's comparison pages keep the pairs that have been examined separate from those that have not.
Editorial synthesis Written from general pharmacology, the development record and what is commonly reported; not a cited finding. Cited findings on this page carry their own tier.
Other compounds in its class
Same class in the registry: Cagrilintide, Retatrutide, Semaglutide, Tirzepatide. Each row shows what that compound's own record states; nothing is inferred across rows.
| Compound | Tier | Publications | RCTs | Record |
|---|---|---|---|---|
| Survodutide | Human clinical trial | 91 | 10 | draft |
| Cagrilintide | Human clinical trial | 105 | 15 | draft |
| Retatrutide | Human clinical trial | 197 | 7 | draft |
| Semaglutide | Approved label | 6,039 | 305 | draft |
| Tirzepatide | Approved label | 2,756 | 131 | draft |
Regulatory status: phase 3 complete in obesity, not yet approved
Registry facts only. Jurisdiction-level status, compounding categories and sport prohibitions need their own cited documents before they appear here.
- Editorial synthesis from general knowledge · primary document to be added to the ledger
Open questions and limitations
What is genuinely unknown, stated plainly. A missing field is not evidence that the outcome is safe, effective, or established.
- SYNCHRONIZE-2 (type 2 diabetes) and SYNCHRONIZE-CVOT (cardiovascular outcomes) have not reported.
- No head-to-head trial against tirzepatide, semaglutide, retatrutide or mazdutide exists.
- No regulatory filing or decision document is in the ledger; the status paragraph is from the trial papers and the sponsor's timeline.
Questions people ask
What is survodutide?
Survodutide (BI 456906) is a once-weekly injectable peptide that activates both the glucagon receptor and the GLP-1 receptor. Zealand Pharma designed it and Boehringer Ingelheim is developing it for obesity, type 2 diabetes and metabolic liver disease. In the phase 3 SYNCHRONIZE-1 trial published in June 2026, adults with obesity lost 12 to 13 percent of body weight over 76 weeks against 5 percent on placebo. It is not yet approved anywhere.
What is the half-life of survodutide?
Long enough for once-weekly injection: the molecule carries a C18 fatty acid chain, the same half-life-extending device as semaglutide, so that it binds albumin and clears over about a week. The abstracts in the ledger state the design principle and the weekly schedule rather than a figure in hours.
Is survodutide available now?
Not as a medicine. As of the sources available on it has completed phase 3 in obesity and metabolic liver disease and is under regulatory review or heading there; no approval is documented, and no licensed pharmacy sells it. Vials sold online as 'survodutide peptide' are unregulated products claiming to contain an investigational drug.
Is survodutide approved?
Not as of the sources available on . Phase 3 trials in obesity without diabetes and in obesity with at-risk liver disease were published in June 2026; the type 2 diabetes phase 3 has published only its baseline; the cardiovascular outcomes trial is enrolling. No approval decision is documented.
How much weight do people lose on survodutide?
In SYNCHRONIZE-1, 725 adults with obesity lost a mean 12.2% on 3.6 mg and 13.0% on 6.0 mg over 76 weeks, against 5.4% on placebo with the same lifestyle counselling. Phase 2 found larger proportional losses in women and at lower starting BMI.
What does survodutide do to the liver?
In SYNCHRONIZE-MASLD, 84.2% of adults with obesity and at-risk metabolic liver disease on 6.0 mg achieved at least a 30% reduction in MRI-measured liver fat, against 24.3% on placebo, alongside weight loss. The glucagon receptor, which drives fat oxidation in the liver, is the reason this result is expected to exceed GLP-1 drugs alone; no head-to-head trial has tested that.
What is the dose of survodutide?
In the phase 3 trials, once-weekly subcutaneous injection titrated over weeks to 3.6 mg or 6.0 mg, with flexibility allowed; the liver trial used 6.0 mg. Phase 2 tested 0.3 to 2.7 mg weekly and twice-weekly schedules in diabetes. The drug is not sold by any pharmacy, so no labelled dose exists.
What are the side effects of survodutide?
Gastrointestinal, as with every drug in the class: nausea most often, diarrhoea about 1.9 times as likely as placebo in a meta-analysis, decreased appetite, all dose-related and reduced by slower titration. Overall adverse-event rates matched placebo in the pooled analysis. Cardiovascular outcomes are still being measured.
How does survodutide compare with tirzepatide?
Indirectly, and unfavourably on the headline number: tirzepatide's pivotal trial reported 15 to 21% at 72 weeks against survodutide's 12 to 13% at 76 weeks, in different populations with different designs. Survodutide's distinctive result is liver fat; tirzepatide's is the larger weight loss and an approval. No trial has compared them.
How does survodutide compare with retatrutide?
Both add glucagon-receptor agonism to GLP-1; retatrutide adds GIP as well and reported about 24% weight loss at 48 weeks in phase 2, with phase 3 ongoing. Survodutide's phase 3 is complete. Neither is approved, and no trial has compared them.
How does survodutide compare with semaglutide?
Semaglutide's pivotal obesity trial reported about 15% at 68 weeks; survodutide's reported 12 to 13% at 76 weeks. The phase 2 diabetes trial included an open-label semaglutide arm for context but was not powered to compare them. Semaglutide is approved with a cardiovascular outcomes trial completed; survodutide's is enrolling.
What is a 'survodutide peptide' vial?
An unregulated product sold online claiming to contain an investigational drug that no regulator has approved and no pharmacy dispenses. There is no public reference standard, no titration guidance and no way for a buyer to verify contents; the trial data describe the sponsor's product, not the vial.
Who makes survodutide?
Zealand Pharma of Denmark designed it; Boehringer Ingelheim licensed it in 2011 and runs the SYNCHRONIZE phase 3 programme. Its development code is BI 456906.
What is the half-life of survodutide?
About a week, by design: a C18 fatty-acid side chain binds albumin, the same principle as semaglutide, which is why the trials dose once weekly. The abstracts in the ledger give the design and schedule rather than a figure in hours.
Is survodutide banned in sport?
Not by name. As an unapproved substance it falls under WADA's S0 category at all times, and anti-doping bodies have the GLP-1 class under review; an athlete should treat it as prohibited.
Sources
Full citations. Every claim above links to one of these by its id.
- 1From Potency Ratios to Target Engagement: Translational Identifiability of Multi-Incretin Receptor Balance
doi-10-22541-authorea-15008173-v1· · preprint - 2Phenotype-Directed Precision Therapeutics: A Framework for Multi-Agonist Therapy in Obesity, MASH and Cardio-Renal-Metabolic Disorders
doi-10-20944-preprints202607-0236-v2· · preprint - 3Phenotype-Directed Precision Therapeutics: A Framework for Multi-Agonist Therapy in Obesity, MASH and Cardio-Renal-Metabolic Disorders
doi-10-20944-preprints202607-0236-v1· · preprint - 4
- 5Survodutide Once Weekly for the Treatment of Adults with Obesity.
pmid-42253238· · peer-reviewed - 6
- 7
- 8
- 9
- 10
- 11
- 12
Show the remaining 14 sources
- 13
- 14Therapeutic horizons in metabolic dysfunction-associated steatohepatitis.
pmid-40590228· · peer-reviewed - 15
- 16
- 17
- 18Emerging pharmacotherapies for obesity: A systematic review.
pmid-39952695· · peer-reviewed - 19
- 20Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.
pmid-38843460· · peer-reviewed - 21
- 22Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial.
pmid-39453356· · peer-reviewed - 23The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.
pmid-38560764· · peer-reviewed - 24
- 25
- 26BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.
pmid-36356832· · peer-reviewed
Reference card
- Compound
- Survodutide, incretin and amylin analogs
- Evidence tier
- Human clinical trial
- Indexed publications
- 91 · 10 RCTs · 15 other clinical trials
- Approval
- not approved · max phase 3
- Routes reported
- subcutaneous
- Reviewed
- Adam Mirando, PharmD,
Study figures are as published in each source and are not recommendations. Print or save this card with its date.
Last reviewed and what changed
Newest first. These are the record's own revision dates, and the same dates feed the sitemap.
- · Reviewed by Adam Mirando, PharmD, on 2026-09-25.
- · Written under the sequencing rule after research/intents/survodutide.json: guide (8 sections incl. a trial table with the June 2026 phase 3 results), FAQ to 12 plus 3 from the map, dose, timeline and adverse-event claims from the abstracts, mechanism (glucagon plus GLP-1), reported-use (gray-market vials), regulatory; a misdrafted interaction claim ('interactive response technology') removed; intent-driven H1 and title. Triage: escalation claims that quoted the NEJM estimand sentence removed.
- · Claims drafted extractively from 23 ledger sources by scripts/draft_claims.py: 32 claims, 17 evidence-table rows. Status researched -> draft.
- · Claims drafted extractively from 23 ledger sources by scripts/draft_claims.py: 36 claims, 17 evidence-table rows. Status researched -> draft.
- · Evidence fetched from Europe PMC and ChEMBL by scripts/fetch_evidence.py; claims not yet written.