On June 8, 2026, Boehringer Ingelheim published full Phase 3 results for survodutide (BI 456906), a once-weekly glucagon/GLP-1 dual agonist licensed from Zealand Pharma. SYNCHRONIZE-1 tested 76 weeks in adults with obesity or overweight without type 2 diabetes. SYNCHRONIZE-MASLD tested 48 weeks in adults with obesity or overweight plus metabolic dysfunction-associated steatotic liver disease (MASLD) with evidence of inflammation or fibrosis.
The company headline is up to 16.6% mean weight loss at 76 weeks on the efficacy estimand, versus 3.2% on placebo (p<0.0001), plus a pre-specified MRI substudy showing up to 34% relative visceral-fat reduction and up to 63.1% liver-fat reduction. Those figures sit in the June 8, 2026 BioSpace copy of the Boehringer release. The same release says the trials were presented at the American Diabetes Association 2026 Scientific Sessions and published in the New England Journal of Medicine (le Roux et al.) and Nature Medicine (Kaplan et al., doi 10.1038/s41591-026-04479-3). Both journals list June 7, 2026 as the online date.
Survodutide is investigational. It is not FDA-approved. The June 8 release does not announce an NDA or any other marketing application. The 16.6% figure is the efficacy estimand (the effect if participants stayed on assigned treatment). The treatment-regimen numbers, which keep people who stopped the drug, are lower.
What survodutide is
Survodutide is a glucagon receptor / GLP-1 receptor dual agonist. Boehringer describes GLP-1 agonism as reducing appetite and increasing satiety, and glucagon agonism as acting on the liver to reduce hepatic fat and affect metabolic function. The company and both papers treat it as an investigational peptide, not an approved obesity or MASH medicine.
It is not semaglutide and not tirzepatide. Those are different approved products with different receptor pairs. Sharing a weekly incretin conversation is not sharing a molecule. Research-vendor vials labeled survodutide or "glucagon/GLP-1" are not the SYNCHRONIZE trial product.
Boehringer holds a global license from Zealand Pharma and is solely responsible for development and commercialization. FDA Fast Track (May 2021) and Breakthrough Therapy (September 2024) designations apply to MASH development. Those are FDA process designations. They are not approvals.
The milligram figures below are trial-design and reported-result numbers. They are not a consumer dosing protocol.
SYNCHRONIZE-1: obesity without type 2 diabetes
ClinicalTrials.gov NCT06066515 is a completed Phase 3, randomized, double-blind, parallel-group, 76-week trial of once-weekly subcutaneous survodutide versus placebo in adults with overweight or obesity and no type 2 diabetes. The registry lists actual enrollment of 726, start on 2023-11-25, primary completion on 2025-12-02, and completion on 2026-02-20. Arms are 3.6 mg, 6.0 mg, and placebo. All participants also received diet and exercise counseling.
The June 8 company release describes 725 adults. le Roux et al. in NEJM also reports 725 randomized and treated participants (241 on 3.6 mg, 242 on 6.0 mg, 242 on placebo). This article uses 725 as the journal and company count and notes that the registry currently lists 726 actual enrollment.
Topline weight-loss headlines first appeared on April 28, 2026, in a Boehringer GlobeNewswire release. That release said the trial met both co-primary endpoints on both estimands and reserved the MRI and full safety package for ADA.
Two estimands matter, and they are not interchangeable.
| Item | Company / registry | Peer-reviewed primary analysis |
|---|---|---|
| Population | Adults with BMI ≥30, or ≥27 plus a weight-related complication, without type 2 diabetes | Same eligibility in the NEJM report |
| N | 725 (company and NEJM). 726 actual on ClinicalTrials.gov | 725 treated (241 / 242 / 242) |
| Duration | 76 weeks | 76 weeks |
| Weekly arms | 3.6 mg, 6.0 mg, or placebo | Same 1:1:1 assignment |
| Efficacy estimand weight change | Up to 16.6% mean loss vs 3.2% placebo (p<0.0001). Company footnote: those p-values are nominal | Not the NEJM primary analysis |
| Treatment-regimen weight change | Company says the trial also met primaries on this estimand | Mean change -12.2% (3.6 mg; 95% CI -13.6 to -10.8), -13.0% (6.0 mg; 95% CI -14.4 to -11.6), -5.4% placebo (95% CI -6.9 to -4.0) |
| ≥5% weight-loss responders (treatment-regimen) | Co-primary on the registry | 72.6% (3.6 mg), 71.9% (6.0 mg), 46.3% placebo (P<0.001 vs placebo) |
| Baseline (NEJM) | Not restated in the June 8 release | Mean age 47.1 years; 40.6% men; mean BMI 37.9; mean weight 108.8 kg |
The efficacy estimand asks what happened if people stayed on treatment for the whole study. The treatment-regimen estimand keeps discontinuations and other intercurrent events in the estimate. NEJM states that the primary efficacy analysis used the treatment-regimen estimand. The 16.6% versus 3.2% pair is the company efficacy-estimand headline from April 28 and June 8. The June 8 footnotes say those efficacy p-values are nominal and are "calculated primarily for descriptive exploration rather than to establish strict, definitive proof of statistical significance."
A pre-specified MRI substudy, reported in the June 8 release from participants with MRI at baseline and end of study while on treatment, showed a relative visceral-fat reduction of up to 34.0%. Lean mass accounted for no more than 10.8% of the change in total tissue mass at the highest dose. The same substudy showed liver-fat reduction of up to 63.1%. Those are company-reported, on-treatment MRI figures. They are not a claim that the average randomized participant lost 34% of visceral fat.
Gastrointestinal events were the most common adverse events. The June 8 release says they were mostly mild to moderate and usually occurred during dose escalation (nausea, vomiting, diarrhea, constipation). Discontinuation because of gastrointestinal events was 19% on survodutide versus 2.9% on placebo. NEJM reports gastrointestinal symptoms in 80.9% (3.6 mg), 89.7% (6.0 mg), and 47.9% (placebo). No deaths were reported in the NEJM abstract. The company said no new safety signals were identified.
SYNCHRONIZE-MASLD: liver fat and weight at 48 weeks
ClinicalTrials.gov NCT06309992 is a completed 48-week Phase 3 trial. The registry title still uses the older NASH wording. The company and the paper use MASLD with evidence of inflammation or fibrosis. Actual enrollment is 218. Start date is 2024-04-02. Primary completion is 2025-10-09. Completion is 2025-12-02. The assigned weekly arm is 6.0 mg versus placebo, plus diet and exercise counseling. Co-primaries are a ≥30% relative MRI-PDFF liver-fat reduction and percent body-weight change, both to week 48.
Kaplan et al. in Nature Medicine, published online June 7, 2026, resolve the enrollment line. Of 508 people screened, 218 were randomized 2:1, and 216 received at least one dose (146 survodutide, 70 placebo). Sites were 31 in the United States and one in Spain. Mean age was 55.8 years. 60.6% were female. Mean BMI was 39.6. Mean weight was 108.3 kg. Mean baseline liver fat was 16.9% by MRI-PDFF. 38.4% had type 2 diabetes. Most participants (90.3%) entered on noninvasive-test evidence of at-risk MASLD; 9.7% had a biopsy-confirmed MASH history within three years. Mean MRE stiffness was 2.8 kPa, consistent with early fibrosis in that cohort.
The paper's statistical plan evaluates the co-primaries primarily on the treatment-regimen estimand. The company June 8 headline uses the supplementary efficacy estimand.
| Endpoint at week 48 | Efficacy estimand (company headline and paper supplement) | Treatment-regimen estimand (paper primary) |
|---|---|---|
| ≥30% relative liver-fat reduction | 84.2% vs 24.3% placebo (p<0.0001) | 68.5% vs 28.6% placebo (p<0.0001) |
| Mean body-weight change | -12.2% vs -1.0% placebo (p<0.0001) | -8.7% vs -1.4% placebo (p<0.0001) |
| Liver fat <5% (normalization) | 61.0% vs 5.7% placebo | Not the paper's primary |
| Mean relative liver-fat change | -58.7% vs -9.5% placebo (ETD -49.2%; 95% CI -61.7 to -36.7; p<0.0001) | Paper reports this with the efficacy / on-treatment analysis |
The 61% normalization figure is a secondary result in both the June 8 release ("up to 6 out of 10") and the Nature Medicine paper (61.0% versus 5.7%). Liver-fat reduction on MRI-PDFF is not histologic MASH resolution and not fibrosis regression on biopsy. Kaplan et al. say a ≥30% MRI-PDFF cut has been associated with a higher chance of histologic improvement in other datasets. Association in prior work is not a SYNCHRONIZE-MASLD biopsy win. This trial was not designed as a registrational F2-F3 histology study.
Safety in the MASLD paper matches the class pattern. Gastrointestinal events were the most common, mostly during the 24-week escalation window, and mostly mild to moderate. They led to discontinuation in 19.9% on survodutide versus 4.3% on placebo. That is a different trial, a different population, and a slightly different discontinuation pair from SYNCHRONIZE-1's 19% versus 2.9%. Do not merge them into one safety table.
What this does not mean
- It is not FDA approval. Survodutide has not been approved for obesity, overweight, MASLD, MASH, or any other use.
- It is not an NDA. The June 8 release does not announce a filing. Fast Track and Breakthrough Therapy are development designations.
- 16.6% is not the treatment-regimen result. The on-treatment efficacy estimand is 16.6% versus 3.2%. NEJM's primary treatment-regimen means are 13.0% and 12.2% versus 5.4% placebo.
- MRI fat cuts are not a MASH histology label. SYNCHRONIZE-1's 34% visceral and 63.1% liver-fat figures are a company-reported, on-treatment MRI substudy. SYNCHRONIZE-MASLD's 84.2% / 61.0% figures are MRI-PDFF, not paired week-48 biopsies for the whole cohort.
- A research-vendor vial is not the trial peptide. SYNCHRONIZE used a controlled investigational product.
- This is not medical advice, and it is not a consumer dosing protocol. 3.6 mg and 6.0 mg are trial arms.
What did not change
Approved weekly incretin products did not change status because survodutide read out. Semaglutide and tirzepatide remain different molecules with their own labels. The PeptidePrices ADA 2026 GLP-1 pipeline roundup covered other incretin readouts from the same meeting. It did not replace this SYNCHRONIZE pair.
LIVERAGE and LIVERAGE-Cirrhosis, the company's Phase 3 MASH fibrosis and compensated-cirrhosis trials, remain ongoing in the June 8 release. SYNCHRONIZE-2 (obesity with type 2 diabetes) and SYNCHRONIZE-CVOT remain part of the listed obesity program. None of those readouts are in this source set.
Gray-market "survodutide" listings also did not become a licensed drug. A COA check can test whether a certificate names a real lab. It cannot turn a catalog vial into BI 456906 from SYNCHRONIZE.
What to watch
- Whether Boehringer files an NDA, and on which indication. Obesity, MASLD imaging, and MASH histology are different packages. No filing is in the June 8 record.
- How regulators treat the two estimands. The 16.6% headline and the 13.0% / 12.2% treatment-regimen means answer different questions.
- LIVERAGE and LIVERAGE-Cirrhosis. Those are the MASH fibrosis and cirrhosis outcomes trials named in the June 8 release.
- Tolerability in practice. Gastrointestinal discontinuation was 19% versus 2.9% in SYNCHRONIZE-1 and 19.9% versus 4.3% in SYNCHRONIZE-MASLD.
- The planned Phase IIIb starts named for later in 2026: SYNCHRONIZE-HERA (women's health), ELEVATE-LIVER (cardiac function in MASLD or early MASH), and SYNCHRONIZE-START (real-world titration and switching). Those are company plans, not results.
For the wider incretin map, see GLP-1s beyond weight loss and the ADA 2026 pipeline roundup. Live semaglutide and tirzepatide pages are price-and-vendor views of different products.
FAQs
Is survodutide FDA-approved?
No. It is an investigational glucagon/GLP-1 dual agonist. FDA Fast Track (May 2021) and Breakthrough Therapy (September 2024) apply to MASH development. They are not approvals. The June 8, 2026 release does not announce an NDA.
What did SYNCHRONIZE-1 show for weight?
On the efficacy estimand, the company reported up to 16.6% mean weight loss at 76 weeks versus 3.2% placebo (p<0.0001; company footnote: nominal). NEJM's treatment-regimen analysis reported -12.2% (3.6 mg) and -13.0% (6.0 mg) versus -5.4% placebo.
What did the MRI substudy show?
In participants with paired on-treatment MRI, the company reported up to 34% relative visceral-fat reduction, lean-mass change no more than 10.8% of total tissue-mass change at the highest dose, and up to 63.1% liver-fat reduction. That is a substudy, not the randomized average.
What did SYNCHRONIZE-MASLD show?
Kaplan et al. reported that 84.2% versus 24.3% reached a ≥30% relative liver-fat cut on the efficacy estimand (68.5% versus 28.6% on the treatment-regimen estimand). Weight change was -12.2% versus -1.0% (efficacy) and -8.7% versus -1.4% (treatment-regimen). 61.0% versus 5.7% reached liver fat under 5%.
Is a research-vendor survodutide vial the SYNCHRONIZE drug?
No. The trials used a controlled investigational product. Catalog listings are a different market.
This article is for general informational purposes only and is not medical advice. Talk to a licensed clinician about personal medical decisions. Survodutide is an investigational peptide studied in controlled trials. Nothing here is a dosing protocol, an availability claim, or a recommendation to obtain an unapproved product.
Continue your research
- Semaglutide price comparison
- Tirzepatide price comparison
- GLP-1s Are Becoming "Everything" Drugs
- What the GLP-1 Pipeline Showed at ADA 2026
- COA Authenticity Checker
Sources
- Boehringer Ingelheim. Survodutide Phase III showed targeted 34% visceral and 63% liver fat reduction. BioSpace reprint. June 8, 2026
- ClinicalTrials.gov NCT06066515. SYNCHRONIZE-1
- ClinicalTrials.gov NCT06309992. SYNCHRONIZE-MASLD
- le Roux CW, et al. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med. Published June 7, 2026. doi 10.1056/NEJMoa2600751
- Kaplan LM, et al. Survodutide in adults with obesity and MASLD: SYNCHRONIZE-MASLD. Nat Med. Published June 7, 2026. doi 10.1038/s41591-026-04479-3
- Boehringer Ingelheim. Survodutide achieved significant weight loss of 16.6% in Phase III. GlobeNewswire. April 28, 2026