Updated August 2026
Survodutide Dosage, Results, Side Effects & MASH Clinical-Trial Guide
Research status: Survodutide (BI 456906) is an investigational, once-weekly glucagon receptor/GLP-1 receptor dual agonist. It is not FDA approved and has no approved dosage. The doses on this page are clinical-trial protocols—not prescribing instructions. FDA Fast Track and Breakthrough Therapy designations for MASH accelerate development and review; they do not mean the drug is approved.
Survodutide is a long-acting peptide engineered to activate two metabolic receptors: GLP-1 receptors, which reduce appetite and support glucose regulation, and glucagon receptors, which may add liver-directed and energy-balance effects.
In the 76-week Phase 3 SYNCHRONIZE-1 trial in adults with obesity but no diabetes, the treatment-regimen analysis found mean weight changes of −12.2% with 3.6 mg, −13.0% with 6.0 mg, and −5.4% with placebo. A different on-treatment efficacy estimand produced the sponsor’s widely quoted “up to 16.6%” result; the two figures answer different questions.
The drug’s clearest potential differentiator is its liver program. In Phase 3 SYNCHRONIZE-MASLD, 6.0 mg produced a ≥30% liver-fat reduction in 84.2% versus 24.3% with placebo under the efficacy estimand. In a biopsy-based Phase 2 MASH trial, improvement in MASH without worsening fibrosis occurred in 47%, 62%, and 43% at 2.4, 4.8, and 6.0 mg versus 14% placebo.
Tolerability is the main unresolved limitation. Gastrointestinal adverse events occurred in 80.9%–89.7% of active-treatment participants in SYNCHRONIZE-1, and adverse events caused discontinuation in 23.7%–24.8% versus 5.4% on placebo.
30-Second Summary
| Question | Answer |
|---|---|
| What is it? | A long-acting, acylated peptide and dual glucagon/GLP-1 receptor agonist (BI 456906) |
| Main mechanism | GLP-1 receptor activation plus lower relative glucagon-receptor activation (~8× more potent at GLP-1R in vitro) |
| Administration studied | Subcutaneous injection, usually once weekly |
| Studied dosage | Phase 2: 0.6–6.0 mg weekly; Phase 3 obesity: titrated to 3.6 or 6.0 mg weekly |
| Strongest obesity result | Week 76: −12.2% / −13.0% (treatment-regimen); up to −16.6% (efficacy estimand) |
| Strongest liver result | 84.2% ≥30% liver-fat reduction; 61.0% reached liver fat <5% (efficacy estimand) |
| Main side effects | Nausea, vomiting, diarrhea, constipation; substantial AE discontinuation |
| Half-life | >100 hours in Phase 1 — supports weekly dosing |
| FDA status | Not approved; Fast Track and Breakthrough Therapy for noncirrhotic MASH F2–F3 |
What Is Survodutide?
Survodutide is an investigational peptide drug developed for obesity and metabolic liver disease. It was discovered through a Zealand Pharma program, licensed to Boehringer Ingelheim, and is now developed and commercialized globally by Boehringer Ingelheim.
Survodutide is sometimes described as “oxyntomodulin-like” because endogenous oxyntomodulin can signal through both glucagon and GLP-1 receptors. Structurally, it was engineered from a glucagon-based peptide scaffold. A C18 fatty-acid component promotes albumin binding and extends exposure.
Survodutide is not the same as semaglutide (GLP-1 only), tirzepatide (GIP/GLP-1), retatrutide (GIP/GLP-1/glucagon), cagrilintide (amylin analog), or other glucagon/GLP-1 dual agonists such as mazdutide or pemvidutide.
Survodutide Dosage Used in Clinical Trials
There is no approved human survodutide dose. Trial target doses should not be converted into a self-treatment schedule. Milligram numbers cannot be compared directly with semaglutide, tirzepatide, or another peptide.
- A target dose is the dose an arm attempted to reach — not proof every participant remained on it.
- Phase 3 protocols allowed delay, interruption, dose reduction, or re-escalation for GI intolerance.
- A trial dose is not an approved dose or evidence that an online product contains the stated amount.
Major research exposures
| Trial / population | Target dose | Frequency | Duration | Study role |
|---|---|---|---|---|
| Phase 2 obesity (NCT04667377) | 0.6, 2.4, 3.6, or 4.8 mg | Weekly SC | 46 weeks | Dose finding |
| SYNCHRONIZE-1 obesity, no T2D | 3.6 or 6.0 mg | Weekly SC | 76 weeks | Confirmatory obesity |
| SYNCHRONIZE-2 obesity + T2D | 3.6 or 6.0 mg | Weekly SC | 76 weeks | Publication pending |
| Phase 2 MASH F1–F3 | 2.4, 4.8, or 6.0 mg | Weekly SC | 48 weeks | Biopsy histology |
| SYNCHRONIZE-MASLD | Titrated to 6.0 mg | Weekly SC | 48 weeks | MRI liver-fat co-primary |
| LIVERAGE / LIVERAGE-Cirrhosis | Titrated to 6.0 mg | Weekly SC | Years | Confirmatory MASH outcomes |
Survodutide Dose Escalation
Escalation is central to interpreting efficacy and safety. Survodutide was not started at the highest maintenance dose in the major trials. Phase 3 generally increased doses at four-week intervals over about 24 weeks toward 3.6 or 6.0 mg.
Slower escalation is pharmacologically sensible, but Phase 3 data do not show that titration fully solves gastrointestinal tolerability limitations — AE discontinuation remained about 24–25% in active obesity arms.
Phase 3 dose-escalation timeline
SYNCHRONIZE schedule — clinical-trial protocol, not approved dosing
Clinical-trial protocol — not approved dosing. Intermediate week-by-week ladders are not presented as official schedules.
Start low
Do not begin at the Phase 3 target dose.
Escalate every ~4 weeks
Approximately weeks 0–24 toward 3.6 or 6.0 mg.
Flexible management
Delay increase, temporarily interrupt, reduce dose, or attempt re-escalation under protocol rules.
Maintenance to week 76
Continue assigned target or protocol-permitted lower dose.
Safety follow-up
~3 weeks after treatment for off-treatment events.
Slower Phase 3 escalation did not eliminate tolerability problems — AE discontinuation remained ~24–25% in active arms.
What Happens at Each Studied Dose?
The clearest dose-response evidence comes from the 46-week Phase 2 obesity trial. These are assigned target-dose arms — not outcomes guaranteed for an individual. The primary planned-treatment analysis is the correct basis for the dose table; the often-cited 18.7% at 4.8 mg was an actual-treatment sensitivity analysis.
Phase 2 dose-response explorer
Week-46 planned-treatment weight change (obesity)
Primary analysis is planned-treatment — not individual predictions
| Dose | Weight Δ | ≥5% / ≥10% / ≥15% | GI / Nausea |
|---|---|---|---|
| Placebo | −2.8% | 25.9% / 9.1% / 2.6% | 42% / 20% |
| 0.6 mg | −6.2% | 53.2% / 24.7% / 10.4% | 57% / 34% |
| 2.4 mg | −12.5% | 74.2% / 59.7% / 39.5% | 86% / 65% |
| 3.6 mg | −13.2% | 79.7% / 56.3% / 39.1% | 75% / 62% |
| 4.8 mg | −14.9%(sens. −18.7%) | 82.8% / 68.8% / 54.7% | 82% / 64% |
Survodutide Results for Weight Loss
SYNCHRONIZE-1 randomized 725 adults without diabetes to 3.6 mg, 6.0 mg, or placebo, alongside diet and activity counseling. The treatment-regimen estimand includes the effect of assignment regardless of early discontinuation — the more pragmatic headline for “what happened after assignment.”
Phase 3 weight-loss estimand toggle
SYNCHRONIZE-1 week 76 — why 13.0% and 16.6% both appear
Effect of assignment, including treatment discontinuation and protocol-defined intercurrent events — the more pragmatic headline.
3.6 mg
−12.2%
n=241
6.0 mg
−13%
n=242
Placebo
−5.4%
n=242
AE discontinuation was 23.7% (3.6 mg) and 24.8% (6.0 mg) versus 5.4% placebo — do not replace treatment-regimen with efficacy when discussing real-world-like effectiveness.
Why some pages report 16.6% instead of 13.0%
Both numbers came from SYNCHRONIZE-1. The efficacy estimand estimates the effect if participants remained on treatment without specified intercurrent events. It is useful for pharmacologic potential among people able to continue — it should not replace the treatment-regimen result when discussing real-world-like effectiveness, especially with substantial discontinuation.
Weight-loss responder chart
SYNCHRONIZE-1 treatment-regimen responders at week 76
- 3.6 mg
- 6.0 mg
- Placebo
Body Composition and Liver Fat in SYNCHRONIZE-1
A prespecified MRI substudy assessed participants with interpretable baseline and end-of-treatment scans while on treatment. Lean-body volume still decreased; “muscle preserved” is too strong.
Body-composition MRI module
SYNCHRONIZE-1 MRI substudy at 6.0 mg target
Total body-fat volume
−27.8%
Visceral-fat volume
−34%vs −11.8% pbo
Liver-fat content
−63.1%vs −24.5% pbo
Lean-body volume
−9.8%
Lean-body volume is not a direct measure of muscle strength or function. Most measured tissue-volume loss was fat, but “muscle preserved” is too strong.
Survodutide Results for MASLD and MASH
SYNCHRONIZE-MASLD was a 48-week trial in adults with obesity and at-risk MASLD. Most disease was identified through noninvasive tests — this was not a confirmatory biopsy trial in advanced MASH. The lack of a significant MRE stiffness difference matters; histologic fibrosis benefit must be established in ongoing LIVERAGE trials.
Liver evidence dashboard
MRI fat ≠ elastography ≠ biopsy histology
≥30% liver-fat reduction
Efficacy · MRI
84.2% vs 24.3% pbo
≥30% liver-fat reduction
Treatment-regimen · MRI
68.5% vs 28.6% pbo
≥50% liver-fat reduction
Efficacy · MRI
75.3% vs 8.6% pbo
≥70% liver-fat reduction
Efficacy · MRI
55.5% vs 2.9% pbo
Liver fat <5%
Efficacy · MRI
61% vs 5.7% pbo
Mean relative liver-fat change
Efficacy · MRI
−58.7% vs −9.5% pbo
Why some pages say “83% improved”
The 83% figure came from an actual-treatment analysis among participants with paired biopsies, not the conservative planned-treatment population. In planned-treatment analysis, the highest dose-arm response for MASH improvement without worsening fibrosis was 62% at 4.8 mg.
Weight-loss mediation
A 2026 post hoc mediation analysis estimated weight loss mediated ~72% of MASH improvement without worsening fibrosis and ~36% of fibrosis improvement without worsening MASH. Consistent with — but not proof of — a weight-independent liver effect.
Survodutide Side Effects
Gastrointestinal symptoms dominate the current safety profile. They were usually mild or moderate and most frequent during escalation, but “usually mild” should not be confused with “unimportant”: GI events caused many participants to stop treatment.
Side-effect comparison
Preserve 3.6 mg and 6.0 mg arms separately
| Adverse event | 3.6 mg | 6.0 mg | Placebo |
|---|---|---|---|
| Any GI adverse event | 80.9% | 89.7% | 47.9% |
| Any AE leading to discontinuation | 23.7% | 24.8% | 5.4% |
| GI AE leading to discontinuation | 17.8% | 20.2% | 2.9% |
| Serious adverse event | 8.3% | 8.3% | 6.2% |
Other safety findings
- Heart rate: Mean increases of roughly 2–4 bpm across trials; CVOT outcomes not yet published.
- Cardiovascular outcomes: Risk factors improved, but survodutide has not been shown to reduce MACE.
- Pancreatic enzymes: Asymptomatic hyperenzymemia more frequent in Phase 2 MASH; Phase 3 MASLD reported no adjudication-confirmed acute pancreatitis in the active arm.
- Thyroid / pregnancy: No approved label — do not copy approved incretin boxed warnings word-for-word onto an investigational molecule.
How Survodutide Works
Survodutide combines an appetite/fullness signal with a liver-focused metabolic signal. Its GLP-1 activity helps people eat less; its glucagon activity may increase hepatic fat oxidation. The intended balance is enough glucagon-receptor activity to add metabolic and liver effects without overwhelming GLP-1 glucose-lowering.
Mechanism visualization
Two pathways converging on weight, liver fat, and metabolic markers
GLP-1 receptor
Brain → lower intake · Pancreas → glucose-dependent insulin · GI → early gastric emptying
Glucagon receptor
Liver → fatty-acid oxidation / liver-fat clearance · Energy expenditure labeled as proposed
Receptor-balance badge: ~1:8 GCGR:GLP-1R activation in vitro
- Target
- GLP-1 receptor
- Tissue / pathway
- Hypothalamus, brainstem, pancreas, GI tract
- Expected effect
- Reduced appetite and energy intake; glucose-dependent insulin; transient gastric emptying slowdown
- Evidence level
- Supported by human PD and clinical data
Survodutide vs Similar Compounds
There is no completed Phase 3 head-to-head obesity trial comparing survodutide with semaglutide, tirzepatide, retatrutide, mazdutide, or pemvidutide. Cross-trial percentages are not direct rankings.
| Compound | Receptor mechanism | U.S. status (Aug 2026) |
|---|---|---|
| Survodutide | Glucagon + GLP-1 | Investigational; not approved |
| Semaglutide | GLP-1 | Approved for several indications |
| Tirzepatide | GIP + GLP-1 | Approved for diabetes and weight management |
| Retatrutide | GIP + GLP-1 + glucagon | Not approved |
| Mazdutide | Glucagon + GLP-1 | Not FDA approved (approved in China) |
| Pemvidutide | Glucagon + GLP-1 | Not approved |
| Resmetirom | THRβ | FDA approved for a specific MASH population |
Survodutide Clinical Trials
Published Phase 3 obesity and MASLD results sit alongside Phase 2 biopsy MASH data and ongoing confirmatory liver and cardiovascular programs.
Clinical-trial explorer
Obesity, MASLD, MASH, T2D, and cardiovascular programs
- Published
SYNCHRONIZE-1
NCT06066515 · Phase 3 · 76 weeks
Obesity/overweight + complication, no diabetes
Dose: 3.6 or 6.0 mg weekly · n=725
−12.2% / −13.0% vs −5.4% (treatment-regimen)
View source → - Published
SYNCHRONIZE-MASLD
NCT06309992 · Phase 3 · 48 weeks
Obesity + at-risk MASLD; ~38% T2D
Dose: Titrated to 6.0 mg · n=216
Both co-primaries met; 84.2% ≥30% fat reduction (efficacy)
View source → - Published
Phase 2 obesity dose-finding
NCT04667377 · Phase 2 · 46 weeks
Adults without diabetes, BMI ≥27
Dose: 0.6–4.8 mg weekly · n=387
−6.2% to −14.9% vs −2.8% placebo (planned-treatment)
View source → - Published
Phase 2 biopsy MASH
NCT04771273 · Phase 2 · 48 weeks · Biopsy
Biopsy-confirmed MASH, F1–F3
Dose: 2.4, 4.8, or 6.0 mg · n=293
47% / 62% / 43% vs 14% placebo
View source → - Published
Phase 2 type 2 diabetes
NCT04153929 · Phase 2 · 16 weeks
T2D on metformin
Dose: 0.3–2.7 mg weekly; exploratory BID arms · n=411
HbA1c down to −1.71 points; weight to −8.7%
View source → - Results pending
SYNCHRONIZE-2
NCT06066528 · Phase 3 · 76 weeks
Obesity with type 2 diabetes
Dose: 3.6 or 6.0 mg
Full efficacy publication not found by Aug 20, 2026
View source → - Results pending
SYNCHRONIZE-CVOT
NCT06077864 · Phase 3 · Event-driven
Overweight/obesity + CV/kidney disease or high risk
Dose: 3.6 or 6.0 mg
Registry completed; outcomes not yet published
View source → - Ongoing
LIVERAGE
NCT06632444 · Phase 3 · Histology @ 52 wk; outcomes ~7 yr · Biopsy
Biopsy-confirmed MASH, F2–F3
Dose: Titrated to 6.0 mg
Recruiting / ongoing
View source → - Ongoing
LIVERAGE-Cirrhosis
NCT06632457 · Phase 3 · ~4.5 years planned · Biopsy
Compensated MASH cirrhosis, F4
Dose: Titrated to 6.0 mg
Recruiting / ongoing
View source →
Evidence-maturity tracker
What is established vs still pending
Weight loss vs placebo
Phase 3 publishedMRI liver fat
Phase 3 publishedBiopsy MASH histology
Phase 2 published; Phase 3 ongoingCardiovascular outcomes
Trial completed / results pendingClinical liver outcomes & mortality
Ongoing (LIVERAGE)Regulatory approval
None
Evidence Quality
| Evidence type | Strength | What remains uncertain |
|---|---|---|
| Human randomized obesity trials | High for 76-week weight vs placebo | Comparative effectiveness; durability after stopping |
| Human MASLD trial | Moderate–high for MRI liver fat | Biopsy fibrosis regression; clinical liver events |
| Human biopsy MASH trial | Moderate | Confirmatory Phase 3 histology and long-term outcomes |
| Cardiovascular evidence | Insufficient for outcomes | MACE, heart failure, kidney outcomes, mortality |
| FDA approval | None | Submission, label, approved dose, contraindications |
Regulatory and Research Status
As of August 20, 2026, survodutide is not approved for marketing by the FDA, EMA, or any other regulatory authority. There is no approved obesity, diabetes, MASLD, MASH, or bodybuilding indication.
- FDA Fast Track and Breakthrough Therapy designations for noncirrhotic MASH with F2–F3 fibrosis.
- EMA PRIME scheme access for MASH with fibrosis.
- SYNCHRONIZE-1 and SYNCHRONIZE-MASLD results published; LIVERAGE programs ongoing.
- SYNCHRONIZE-CVOT listed completed in the registry; outcome results not yet published.
- Expedited designations are development pathways — not marketing authorization.
Frequently Asked Questions
What is survodutide?
Survodutide is an investigational once-weekly peptide that activates glucagon and GLP-1 receptors. It is being developed for obesity and metabolic liver disease.
What is the survodutide dosage?
There is no approved survodutide dosage. Clinical trials titrated participants to target doses ranging from 0.6 to 6.0 mg weekly depending on the study.
How much weight did people lose with survodutide?
In Phase 3 SYNCHRONIZE-1, mean weight change at 76 weeks was −12.2% with 3.6 mg and −13.0% with 6.0 mg versus −5.4% with placebo under the treatment-regimen estimand. The on-treatment efficacy estimand produced up to −16.6%.
Why is 18.7% weight loss also reported?
The 18.7% figure came from an actual-treatment sensitivity analysis in the Phase 2 4.8 mg group. The primary planned-treatment result for that arm was −14.9%.
What are the most common survodutide side effects?
Nausea, vomiting, diarrhea, and constipation. In Phase 3 obesity research, GI adverse events occurred in 80.9% at 3.6 mg and 89.7% at 6.0 mg versus 47.9% with placebo.
How often did people stop because of side effects?
In SYNCHRONIZE-1, 23.7% at 3.6 mg and 24.8% at 6.0 mg discontinued because of adverse events versus 5.4% on placebo.
Is survodutide FDA approved?
No. Survodutide is investigational and has no FDA-approved indication or dose as of August 20, 2026.
Does Breakthrough Therapy designation mean it is approved?
No. Breakthrough Therapy designation is a development and review pathway, not marketing authorization.
Does survodutide treat fatty liver disease?
It is not approved to treat MASLD or MASH, but trials show strong liver-fat reductions and encouraging biopsy-based MASH findings. Phase 3 LIVERAGE trials must still establish histologic and long-term clinical benefit.
Does survodutide preserve muscle?
Survodutide reduced mostly fat volume in an MRI substudy, but lean-body volume also decreased by 9.8% at the highest dose. The study did not establish preservation of muscle strength, function, or quality.
Is survodutide better than semaglutide or tirzepatide?
No direct Phase 3 head-to-head trial has established that. Survodutide has a distinct glucagon/GLP-1 mechanism and strong liver-fat data, but cross-trial weight-loss comparisons cannot prove superiority.
Does survodutide reduce cardiovascular risk?
That has not been established. Blood pressure, lipids, and other risk markers improved, but dedicated cardiovascular-outcomes results are not yet published.
Can survodutide be bought legally online?
There is no approved commercial survodutide product. Online “research” products are not the regulated investigational formulation and may be mislabeled, contaminated, incorrectly concentrated, or nonsterile.
References
le Roux CW, et al.
Survodutide once weekly for the treatment of adults with obesity (SYNCHRONIZE-1)N Engl J Med. 2026.
Kaplan LM, et al.
Survodutide in adults with obesity and MASLD (SYNCHRONIZE-MASLD)Nat Med. 2026.
le Roux CW, et al.
Phase 2 obesity dose-finding trial of survodutideLancet Diabetes Endocrinol. 2024.
Sanyal AJ, et al.
Phase 2 randomized trial of survodutide in MASH and fibrosisN Engl J Med. 2024.
Blüher M, et al.
Dose-response effects on HbA1c and bodyweight of survodutide in T2DDiabetologia. 2024.
Noureddin M, et al.
Weight reduction-dependent/-independent effects of survodutide on liver endpointsHepatology. 2026.
ClinicalTrials.gov
SYNCHRONIZE-CVOTNCT06077864 — outcomes pending.
ClinicalTrials.gov
LIVERAGE Phase 3 MASH programNCT06632444 · NCT06632457.
Important Safety Information
Survodutide (BI 456906) is an investigational glucagon/GLP-1 dual agonist. It is not FDA approved, has no approved dosage, and is not an established compounded-drug regimen.
Gastrointestinal adverse events and treatment discontinuation were substantial in Phase 2 and Phase 3. Cardiovascular and long-term liver-outcome results are not yet established.
This page is an evidence reference for educational purposes. It is not a prescribing, self-injection, or reconstitution guide.