Survodutide Clinical Development
Survodutide is being developed across multiple indications—obesity, type 2 diabetes, and MASH (fatty liver disease). Here's the current state of clinical development:
- Phase 2 Obesity (Complete): 18.7% weight loss at 46 weeks, 40% achieved ≥20% loss[1]
- Phase 2 MASH (Complete): Up to 62% MASH resolution (NEJM 2024)[2]
- Phase 3 SYNCHRONIZE-1: 726 patients with obesity (no T2D), 76 weeks, enrolled[3]
- Phase 3 SYNCHRONIZE-2: 755 patients with obesity + T2D, 76 weeks, enrolled[3]
- Phase 3 SYNCHRONIZE-CVOT: Cardiovascular outcomes trial, ongoing
- Phase 3 LIVERAGE: MASH trials (~3,390 patients), initiated Oct 2024[4]
Phase 2 Obesity Trial
Design: 46-week, randomized, double-blind, placebo-controlled, dose-finding trial in 386 adults with BMI ≥27 kg/m² without type 2 diabetes. Published in Lancet Diabetes & Endocrinology (Feb 2024).[1]
Weight Loss by Dose (Week 46)
| Dose | Mean Weight Loss | vs. Placebo |
|---|---|---|
| 0.6 mg | -6.2% | -3.4% |
| 2.4 mg | -12.5% | -9.7% |
| 3.6 mg | -13.2% | -10.4% |
| 4.8 mg (all randomized) | -14.9% | -12.1% |
| 4.8 mg (completers) | -18.7% | -15.9% |
| Placebo | -2.8% | — |
Responder Rates (4.8mg Dose)
| Weight Loss Threshold | Survodutide | Placebo |
|---|---|---|
| ≥5% weight loss | 82.8% | 25.9% |
| ≥10% weight loss | 68.8% | ~4% |
| ≥15% weight loss | 67% | 4.3% |
| ≥20% weight loss | 40% | 0% |
Weight Loss Not Plateaued
At 46 weeks, weight loss curves were still trending downward with no plateau observed. This suggests additional weight loss could be achieved with longer treatment—being evaluated in the 76-week Phase 3 trials.
Phase 2 MASH Trial
Design: 48-week, randomized, placebo-controlled trial in 293 adults with biopsy-confirmed MASH and fibrosis (stages F1-F3). Published in New England Journal of Medicine.[2]
Key Liver Endpoints
| Endpoint | Survodutide | Placebo |
|---|---|---|
| MASH improvement (no worsening fibrosis) | 47-62% | 14% |
| Best result (4.8mg dose) | 62% | 14% |
| ≥1 stage fibrosis improvement | 34-36% | 22% |
| ≥30% liver fat reduction | 57-67% | 14% |
Significance: These results led to FDA Breakthrough Therapy designation for MASH (September 2024) and initiated the Phase 3 LIVERAGE program.
Phase 3 SYNCHRONIZE Program
| Trial | Population | N | Duration | Status |
|---|---|---|---|---|
| SYNCHRONIZE-1 | Obesity without T2D | 726 | 76 weeks | Enrolled |
| SYNCHRONIZE-2 | Obesity with T2D | 755 | 76 weeks | Enrolled |
| SYNCHRONIZE-CVOT | CV outcomes | TBD | Long-term | Ongoing |
SYNCHRONIZE Trial Design[3]
- Randomization: Survodutide 3.6mg or 6.0mg weekly vs. placebo
- Dose flexibility: Extended escalation with flexible dosing for GI tolerability
- Primary endpoints: % change in body weight; proportion achieving ≥5% loss at week 76
- Secondary endpoints: ≥10%, ≥15%, ≥20% weight loss; blood pressure; HbA1c (SYNCHRONIZE-2)
- Enrollment: Completed November 2023 (SYNCHRONIZE-1) and June 2024 (SYNCHRONIZE-2)
- Results expected: H1 2026
Phase 3 LIVERAGE Program
Boehringer Ingelheim initiated Phase 3 MASH trials in October 2024 following FDA Breakthrough Therapy designation:[4]
| Trial | Population | N | Status |
|---|---|---|---|
| LIVERAGE | MASH + fibrosis F2/F3 | ~1,800 | Enrolling |
| LIVERAGE-Cirrhosis | MASH + cirrhosis F4 | ~1,590 | Enrolling |
How to Enroll in Survodutide Trials
- ClinicalTrials.gov: Search "survodutide" or "BI 456906"
- SYNCHRONIZE-1/2: Enrollment closed (completed)
- SYNCHRONIZE-CVOT: May have sites still enrolling
- LIVERAGE: MASH trials initiated Oct 2024—may be actively enrolling
- Eligibility (typical): BMI ≥30 (or ≥27 with comorbidities), age 18-75
Note: Boehringer Ingelheim is a major pharmaceutical company with extensive global trial infrastructure. Sites are available across North America, Europe, and Asia.
FAQs
The 46-week duration was designed for dose-finding before investing in longer Phase 3 trials. Importantly, weight loss had not plateaued at 46 weeks—curves were still trending downward. The 76-week SYNCHRONIZE Phase 3 trials will show longer-term efficacy and whether weight loss continues to increase.
Direct comparison is limited by different trial durations:
- Survodutide: 18.7% at 46 weeks (completers)
- Tirzepatide (SURMOUNT-1): 20.9% at 72 weeks
- Semaglutide (STEP 1): 14.9% at 68 weeks
- Retatrutide: 24.2% at 48 weeks (Phase 2)
Given that survodutide's weight loss hadn't plateaued, the 76-week Phase 3 results may show comparable final efficacy to tirzepatide.
Survodutide's glucagon receptor activation may directly improve liver fat metabolism. Phase 2 MASH results published in NEJM showed:
- 47-62% MASH resolution without worsening fibrosis (vs. 14% placebo)
- 62% at optimal 4.8mg dose—best result observed
- Up to 67% achieved ≥30% liver fat reduction
- 34-36% fibrosis improvement (vs. 22% placebo)
These results led to FDA Breakthrough Therapy designation—the Phase 3 LIVERAGE program is now underway.
Sources & References
- le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol. 2024;12(3):162-173. https://pubmed.ncbi.nlm.nih.gov/38330987/
- Sanyal AJ, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024;391:311-319. https://pubmed.ncbi.nlm.nih.gov/38847460/
- Wharton S, et al. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE-1 and -2). Obesity. 2025;33(1):44-54. https://pubmed.ncbi.nlm.nih.gov/39495965/
- Boehringer Ingelheim. Boehringer Ingelheim to advance survodutide into three global Phase III studies in obesity. August 2023. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/obesity/survodutide-phase-iii-study-weight-loss
Last updated October 6, 2026
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