Overview
Overview
Survodutide (BI 456906) is an investigational dual GLP‑1/glucagon receptor agonist under development for obesity and metabolic liver disease[1][2]. In phase 2 trials, once‑weekly subcutaneous dosing (0.6–4.8 mg) produced dose‑dependent weight loss of 12.5–14.9% versus placebo over 46 weeks[1]. This educational protocol presents a once‑weekly subcutaneous titration approach using a practical dilution for clear insulin‑syringe measurements. Reconstitute: Add 2.0 mL bacteriostatic water → 5 mg/mL
- Category
- Weight Loss
- Routes
- subcutaneous
Mechanism
Survodutide
Mechanism of action
Mechanism of action
Survodutide acts on two targets at the same time: the GLP-1 receptor and the glucagon receptor . That is why it is grouped with newer obesity peptides like tirzepatide and retatrutide, but it is not the same as either one. In plain English: GLP-1 may lower appetite and slow how fast food leaves the stomach. Glucagon may raise energy use , meaning the body may burn more calories at rest. Glucagon also acts in the liver, which is why Survodutide is being studied for MASH. In research papers, Survodutide is called a dual agonist because one peptide molecule turns on both receptors. It also has a fatty-acid tail, similar to semaglutide, which helps it last long enough for once-weekly dosing. In Phase 2, around 16.6% of survodutide participants reported decreased appetite vs 3.4% on placebo. Preclinical work showed Survodutide raised energy use in animal models and lowered liver fat. Glucagon receptors are common in the liver, which is why Survodutide is also being tested in MASH and MASH-cirrhosis trials.
Key research findings
- 01
Survodutide (BI 456906) is a once-weekly dual glucagon (GCG) and GLP-1 receptor agonist (mechanistic / human study).
- 02
In Phase 2 obesity research, survodutide produced dose-dependent body-weight reduction (human study, Phase 2).
- 03
Phase 3 SYNCHRONIZE obesity trials reported positive primary-endpoint results, with substantial reductions in liver fat in associated analyses (human study, Phase 3; SYNCHRONIZE-1 published in the New England Journal of Medicine, 2025).
- 04
The compound is also studied in metabolic dysfunction-associated steatohepatitis (MASH) research (LIVERAGE Phase 3 program) and received FDA Breakthrough Therapy designation in that research context in 2024 (human study; regulatory designation).
- 05
Gastrointestinal effects were the most commonly observed effects in research (human study observation).
Primary source: Phase 3 obesity (SYNCHRONIZE-1): 725 adults, 76 weeks, average 16.6% weight loss vs 3.2% placebo. 85.1% reached ≥5% loss. Topline reported by Boehringer Ingelheim, April 28, 2026. Phase 2 obesity (Le Roux et al., Lancet Diabetes & Endocrinology, 2024): 387 adults, 46 weeks, with more weight loss at higher weekly doses. The 4.8 mg arm reached around 14.9% loss in the main analysis, or about 18.7% among people who completed the trial. Phase 2 MASH (NEJM, 2024): 295 adults with MASH and liver scarring. More people on Survodutide improved than on placebo, but stomach and gut observed effects were common. Phase 2 type 2 diabetes (Blüher et al., Diabetologia, 2023): Compared to placebo and open-label semaglutide. Survodutide reduced HbA1c by ~1.5% versus placebo, comparable to 1.0 mg/week semaglutide. Systematic review and meta-analysis (PMC, 2025): A pooled review of randomized Survodutide trials in obesity. It supported the dose-related weight-loss finding and the stomach-and-gut observed effect pattern.
Pharmacokinetic profile
Single-dose plasma curve over 24h. Shaded band = commonly-cited therapeutic window. Illustrative only.
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
Dose‑dependent weight loss of 12.5–14.9% (vs placebo) over 46 weeks in phase 2 obesity trials[1].
Improvements in liver‑related biomarkers in NAFLD/NASH populations[2].
Meta‑analysis confirms consistent weight‑loss efficacy across multiple randomized controlled trials[5].
Protocol Reference
Protocol reference
Commonly cited research range: 0.6–6 mg, weekly.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
46 weeks (0.6 mg arm)
0.6 mg
46 weeks (2.4 mg arm)
2.4 mg
46 weeks (3.6 mg arm)
3.6 mg
46 weeks (4.8 mg arm)
4.8 mg
Weeks 0–20 (Dose-increase phase)
Escalating to assigned arm
Weeks 20–46 (Steady-dose phase)
Assigned arm dose held steady
76 weeks (Phase 3 SYNCHRONIZE-1 — extended exposure)
Not stated as a fixed mg value in the topline release
| Phase | Reference amount | Units / volume |
|---|---|---|
| 46 weeks (0.6 mg arm) | 0.6 mg | 12 units (0.12 mL) |
| 46 weeks (2.4 mg arm) | 2.4 mg | 48 units (0.48 mL) |
| 46 weeks (3.6 mg arm) | 3.6 mg | 72 units (0.72 mL) |
| 46 weeks (4.8 mg arm) | 4.8 mg | 96 units (0.96 mL) |
| Weeks 0–20 (Dose-increase phase) | Escalating to assigned arm | — |
| Weeks 20–46 (Steady-dose phase) | Assigned arm dose held steady | — |
| 76 weeks (Phase 3 SYNCHRONIZE-1 — extended exposure) | Not stated as a fixed mg value in the topline release | — |
Titration protocol
- 46 weeksStart0.6 mg
Lowest studied dose. Once weekly, subcutaneous. Rotate injection sites.
- 46 weeksBuild2.4 mg
Mid dose. Once weekly, subcutaneous. Rotate injection sites.
- 46 weeksBuild3.6 mg
Mid-high dose. Once weekly, subcutaneous. Rotate injection sites.
- 46 weeksBuild4.8 mg
Top dose studied. Once weekly, subcutaneous. Rotate injection sites.
- Weeks 0–20BuildEscalating to assigned arm
The dose went up during the first 20 weeks. Once weekly.
- Weeks 20–46BuildAssigned arm dose held steady
Dose stayed steady for the next 26 weeks — hold, do not increase further. Once weekly.
- 76 weeksMaintenanceNot stated as a fixed mg value in the topline release
Phase 3 SYNCHRONIZE-1. The dose increase was slower and more flexible than in Phase 2. Once weekly.
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️01 Wipe the vial top — Use a fresh alcohol swab on the rubber stopper of both the survodutide vial and the BAC water vial.
- 02🧴Draw 2 mL bacteriostatic water into a sterile syringe — this 10 mg vial yields 5 mg/mL.
- 03💉03 Add slowly — Insert the needle and let the water run down the inside wall of the survodutide vial, not directly onto the powder.
- 04💧04 Swirl, do not shake — Gently swirl or roll the vial between your hands until the powder dissolves into a clear solution. Shaking can damage the peptide.
- 05🔄05 Inspect — The solution should look clear with no cloudiness or particles. If it looks off, do not use the vial.
- 06🏷️06 Label and refrigerate — Write the reconstitution date on the vial. Store at 2 to 8 °C (35.6 to 46.4 °F).
- 07❄️08 Important: This guide is for educational purposes only and is not medical advice. For research use only. Not for human consumption.
Additional storage notes
-4 °F (-20 °C) or colder — Best for long storage. Keep dark and dry.
35.6 to 46.4 °F (2 to 8 °C) — Acceptable for short transit and short holds.
35.6 to 46.4 °F (2 to 8 °C) — Refrigerate. Use within the BAC water shelf window.
Clear after mixing — Cloudy or particulate solution means stop using it.
Clinical Evidence
Clinical evidence
Phase 2 clinical trials report body-weight reduction and metabolic-liver research endpoints; it remains investigational.
Phase 3 obesity (SYNCHRONIZE-1): 725 adults, 76 weeks, average 16.6% weight loss vs 3.2% placebo. 85.1% reached ≥5% loss. Topline reported by Boehringer Ingelheim, April 28, 2026. Phase 2 obesity (Le Roux et al., Lancet Diabetes & Endocrinology, 2024): 387 adults, 46 weeks, with more weight loss at higher weekly doses. The 4.8 mg arm reached around 14.9% loss in the main analysis, or about 18.7% among people who completed the trial. Phase 2 MASH (NEJM, 2024): 295 adults with MASH and liver scarring. More people on Survodutide improved than on placebo, but stomach and gut observed effects were common. Phase 2 type 2 diabetes (Blüher et al., Diabetologia, 2023): Compared to placebo and open-label semaglutide. Survodutide reduced HbA1c by ~1.5% versus placebo, comparable to 1.0 mg/week semaglutide. Systematic review and meta-analysis (PMC, 2025): A pooled review of randomized Survodutide trials in obesity. It supported the dose-related weight-loss finding and the stomach-and-gut observed effect pattern.
- 01Survodutide (BI 456906) is a once-weekly dual glucagon (GCG) and GLP-1 receptor agonist (mechanistic / human study).
- 02In Phase 2 obesity research, survodutide produced dose-dependent body-weight reduction (human study, Phase 2).
- 03Phase 3 SYNCHRONIZE obesity trials reported positive primary-endpoint results, with substantial reductions in liver fat in associated analyses (human study, Phase 3; SYNCHRONIZE-1 published in the New England Journal of Medicine, 2025).
- 04The compound is also studied in metabolic dysfunction-associated steatohepatitis (MASH) research (LIVERAGE Phase 3 program) and received FDA Breakthrough Therapy designation in that research context in 2024 (human study; regulatory designation).
- 05Gastrointestinal effects were the most commonly observed effects in research (human study observation).
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to Survodutide.
- 01Boehringer Ingelheim. Results from Phase III SYNCHRONIZE-1 obesity trial (press release, April 28, 2026). Boehringer Ingelheim (2026)et al. (2026)
- 02Le Roux CW, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. The Lancet Diabetes & Endocrinology (2024)et al. (2024)
- 03Sanyal AJ, Bedossa P, Fraessdorf M, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. New England Journal of Medicine (2024)et al. (2024)
- 04Blüher M, Rosenstock J, Hoefler J, Manuel R, Hennige AM. Dose-response effects on HbA1c and bodyweight reductions with a dual glucagon/GLP-1 receptor agonist, survodutide, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia (2024)et al. (2024)
- 05Zimmermann T, Thomas L, Baader-Pagler T, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Molecular Metabolism (2022)et al. (2022)
- 06Authors et al. Evaluating the efficacy and safety of survodutide for obesity: a systematic review and meta-analysis of randomized controlled trials. PMC (peer-reviewed meta-analysis) (2025)et al. (2025)
- 07Mikhail N, Wali S. Survodutide, a promising agent with novel mechanism of action for treatment of obesity and type 2 diabetes. Journal of Endocrinology and Disorders (2024)et al. (2024)
- 08ClinicalTrials.gov. A Study to Test How Well Different Doses of BI 456906 Help People With Overweight or Obesity Lose Weight (NCT04667377, Phase 2). ClinicalTrials.gov (2024)et al. (2024)
- 09ClinicalTrials.gov. A Study to Test Whether Survodutide (BI 456906) Helps People Living With Overweight or Obesity Lose Weight (SYNCHRONIZE-1, NCT06066529). ClinicalTrials.gov (2026)et al. (2026)
- 10U.S. Food and Drug Administration. Drugs@FDA: search for survodutide approval status (no approved product as of June 2026). FDA.gov (2026)et al. (2026)
Observed Effects
Observed effects in cited research
Phase 2 obesity trial reported rates
- Any stomach or gut observed effect: 75% on Survodutide vs 42% on placebo .
- Stopped because of observed effects: 25% on Survodutide vs 4% on placebo . This was mostly during the fast 20-week dose increase.
- Serious observed effects: 4.2% on Survodutide vs 6.5% on placebo .
- Notable single events: one case of dehydration with kidney failure and one case of angioedema, a serious swelling reaction.
Phase 2 MASH trial reported rates
- Nausea: 66% on survodutide vs 23% on placebo .
- Diarrhea: 49% on survodutide vs 23% on placebo .
- Vomiting: 41% on survodutide vs 4% on placebo .
- Stopped because of observed effects: 20% on Survodutide vs 3% on placebo . Most were stomach and gut observed effects during dose increase.
Phase 3 SYNCHRONIZE-1 safety signal
- Boehringer reported that stomach and gut observed effects in SYNCHRONIZE-1 were mild to moderate and most common while the dose was going up. No new safety concerns were reported in the topline release. Full safety data is due at ADA 2026 in June.
GLP-1 class cautions
- Pancreatitis: GLP-1 drugs carry a pancreas inflammation warning.
- Medullary thyroid cancer: GLP-1 drugs carry a thyroid cancer warning based on animal data.
- Heart rate: a small heart-rate increase was reported with survodutide.
- Hypoglycemia: higher risk if combined with insulin or sulfonylureas.
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Investigational compound currently in clinical development; not approved for general use. Consult a licensed healthcare professional for any clinical decisions.
- Pregnancy and breastfeeding: not studied in these groups. Avoid.
- Personal or family history of medullary thyroid cancer or MEN 2: this is a common warning for GLP-1 drugs.
- History of pancreatitis: GLP-1 drugs carry a pancreas inflammation warning.
- Severe stomach or gut disease: nausea, vomiting, diarrhea, and constipation are common with Survodutide.
- Diabetes treated with insulin or sulfonylureas: blood sugar may need close medical adjustment.
- Children and teenagers: no pediatric data exists.
- Known peptide allergies: one Phase 2 participant had angioedema, a serious swelling reaction.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| Survodutidethis | An investigational long-acting dual agonist of GLP-1 and glucagon receptors studied for appetite regulation and increased energy expenditure. | subcutaneous | Investigational / RUO |
| Tirzepatide | Activates both GIP and GLP-1 receptors, providing synergistic effects on insulin secretion, glucose control, and appetite regulation. | subcutaneous | Investigational / RUO |
| 5-Amino-1MQ | Inhibits nicotinamide N-methyltransferase (NNMT), increasing NAD+ availability and enhancing mitochondrial metabolism. | oral, subcutaneous | Investigational / RUO |
| Adipotide | A peptidomimetic that targets prohibitin on the vasculature of white adipose tissue and delivers a pro-apoptotic sequence, studied for selective reduction of fat-tissue blood supply. | subcutaneous | Investigational / RUO |
| AICAR | A cell-permeable nucleoside phosphorylated intracellularly to ZMP, an AMP-mimetic that activates AMP-activated protein kinase (AMPK), shifting cells toward oxidative metabolism. | subcutaneous | Investigational / RUO |
| TB-500 | Upregulates actin, promotes cell migration, reduces inflammation, and stimulates wound healing and tissue repair. | subcutaneous, intramuscular | Investigational / RUO |
| Tesamorelin | Binds to GHRH receptors to stimulate endogenous GH production. Preferentially reduces abdominal fat accumulation. | subcutaneous | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
Survodutide is a 29-amino-acid peptide developed by Boehringer Ingelheim with Zealand Pharma. Its research code is BI 456906. It acts on both the GLP-1 receptor and the glucagon receptor, which is why it is called a dual agonist.
No. As of June 2026, survodutide is investigational and is not FDA-approved for any human use. The Phase 3 SYNCHRONIZE-1 trial reported positive topline results on April 28, 2026, and full data is due at the ADA 2026 Scientific Sessions in June.
In the Phase 3 SYNCHRONIZE-1 trial, adults with obesity or overweight without type 2 diabetes lost an average of 16.6% of body weight at 76 weeks, versus 3.2% on placebo. 85.1% of survodutide participants reached at least a 5% weight loss versus 38.8% on placebo.
The Phase 2 obesity trial used once-weekly subcutaneous arms of 0.6 mg, 2.4 mg, 3.6 mg, or 4.8 mg, with a 20-week dose escalation followed by 26 weeks of maintenance. Phase 3 SYNCHRONIZE-1 used an extended, more flexible escalation. This is trial-protocol reporting, not a dosing recommendation.
Survodutide is not available by prescription in the United States as of June 2026. Some research suppliers sell it under research-use-only labels, but those products are not regulated as prescription drugs and are not intended for human use. Always confirm current FDA status before drawing conclusions.
Both are investigational once-weekly subcutaneous peptides. Survodutide targets GLP-1 and glucagon. Retatrutide targets GLP-1, GIP, and glucagon. In headline trials, retatrutide reported higher top-arm weight loss than Survodutide, but the two have not been compared head-to-head.
Tirzepatide is GLP-1 plus GIP. Survodutide is GLP-1 plus glucagon. Tirzepatide is FDA-approved for type 2 diabetes (Mounjaro) and for obesity (Zepbound). Survodutide is still investigational. No head-to-head trial has been published.
The most common Survodutide observed effects are nausea, vomiting, diarrhea, and constipation. In the Phase 2 obesity trial, around 75% of Survodutide participants reported a stomach or gut observed effect versus 42% on placebo. Most happened during the fast 20-week dose increase. Phase 3 SYNCHRONIZE-1 reported mostly mild to moderate stomach and gut observed effects with a slower dose increase.
Groups that should avoid Survodutide outside a clinical trial include pregnant or breastfeeding people, people with a personal or family history of medullary thyroid cancer or MEN 2, people with pancreatitis history, people with severe stomach or gut disease, children and teenagers, and anyone with known peptide allergies.
For research-use vials, a common approach is to add 1.0 to 2.0 mL of bacteriostatic water per vial. A 6 mg vial with 1.0 mL of BAC water gives 6.0 mg/mL; a 10 mg vial with 1.0 mL gives 10.0 mg/mL. On a U-100 insulin syringe, 1 unit equals 0.01 mL. Swirl gently, do not shake, and refrigerate after mixing.
LIVERAGE and LIVERAGE-Cirrhosis are Phase 3 Survodutide trials for MASH, a serious fatty liver disease. They include adults with moderate to advanced liver scarring, including cirrhosis. Results are expected later in 2026.
No. This page is an educational research-context reference. Survodutide is not FDA-approved and is not available by prescription. Talk to a qualified clinician before considering any peptide.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.