Survodutide: Boehringer's GLP-1/Glucagon Dual

TL;DR

Boehringer's dual GLP-1/glucagon. 62% MASH resolution in Phase 2. SYNCHRONIZE Phase 3 underway.
What is it? A once-weekly subcutaneous dual agonist of the glucagon and GLP-1 receptors (BI 456906) from Boehringer Ingelheim and Zealand Pharma. Chimeric backbone with an albumin-binding fatty-acid tail.
What does it do? GLP-1 arm brings appetite suppression, slowed gastric emptying, and glucose-dependent insulin. Glucagon arm adds hepatic fatty-acid oxidation and raised energy expenditure. That differentiates it from GLP-1-only and GLP-1/GIP drugs.
Does the evidence hold up? Phase 2 (Lancet Diabetes Endocrinol 2024) showed placebo-adjusted weight loss up to ~12 percentage points at 46 weeks. Phase 2 MASH (Sanyal, NEJM 2024, PMID 38847460) reported 62% MASH resolution without fibrosis worsening at 4.8 mg. Phase 3 SYNCHRONIZE program active.
Who uses it? Clinical-trial participants only. Not available through any approved prescription as of April 2026. Research-peptide vendors supply for lab use.
Bottom line? Phase 2 wins already stand up. Phase 3 SYNCHRONIZE decides pricing and label.

What It Is

Survodutide, developmentally coded BI 456906, is a once-weekly subcutaneous peptide dual agonist of the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R). The molecule was designed at Boehringer Ingelheim with a backbone combining glucagon-like and GLP-1-like structural motifs, conjugated to a fatty-acid chain that enables albumin binding and supports the once-weekly dosing profile. The program is co-developed with Zealand Pharma (Copenhagen), whose long-standing glucagon-analog chemistry underpins the glucagon arm of the molecule.

Dual GLP-1/glucagon agonism is a distinct therapeutic concept from the GLP-1/GIP dual agonism represented by tirzepatide. GLP-1 agonists reduce body weight primarily by suppressing appetite and slowing gastric emptying; glucagon agonism contributes complementary effects on hepatic fatty acid oxidation, thermogenesis, and energy expenditure. The combination is pharmacologically rational for patients in whom reducing visceral and hepatic fat — rather than only body weight — is the clinical priority, including patients with metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and fibrosis.

Survodutide's clinical program advanced rapidly through Phase 1 and Phase 2 beginning around 2020 and is now in a coordinated Phase 3 portfolio covering obesity (SYNCHRONIZE-1, SYNCHRONIZE-2), cardiovascular outcomes (SYNCHRONIZE-CVOT), and additional MASH and type 2 diabetes studies. As of April 2026, survodutide has not received marketing approval in any jurisdiction. All published human data remain Phase 1 and Phase 2.

In the broader competitive landscape, survodutide is one of three advanced GLP-1-pathway combination assets — alongside Eli Lilly's retatrutide (triple agonist GLP-1/GIP/glucagon) and mazdutide (Innovent / Lilly GLP-1/glucagon). Each explores a different trade-off between weight-loss magnitude, hepatic-fat clearance, glycemic effect, and tolerability. Survodutide's positioning within this field will be determined by its Phase 3 efficacy versus tirzepatide and retatrutide and, critically, by its hepatic-fat and fibrosis-stage data in the MASH indication where the glucagon arm is most mechanistically differentiating.

Mechanism of Action

Survodutide's pharmacology reflects balanced agonism at two mechanistically distinct receptors. The molecule is a full agonist at both GCGR and GLP-1R, and its observed clinical effects combine both arms in parallel.

GLP-1 receptor agonism — Binds the Gαs-coupled GLP-1 receptor on pancreatic β-cells, hypothalamic neurons, gastric smooth muscle, and cortical and brainstem feeding circuits. Drives glucose-dependent insulin secretion, suppresses glucagon from α-cells under hyperglycemic conditions, slows gastric emptying, and reduces food intake via hypothalamic and hindbrain pathways (area postrema, nucleus tractus solitarius, arcuate POMC neurons).
Glucagon receptor agonism — Binds the Gαs-coupled glucagon receptor on hepatocytes, adipose tissue, and the CNS. Increases hepatic fatty acid oxidation, reduces hepatic triglyceride accumulation (steatosis), and raises energy expenditure via brown adipose tissue activation and increased resting metabolic rate. This is the mechanistic arm absent from pure GLP-1 agonists and from GLP-1/GIP dual agonists.
Hepatic lipid clearance — The glucagon arm's effect on the liver is quantitatively significant. In the Phase 2 MASH trial (Sanyal 2024, PMID 38847460), decreases in liver fat content by ≥30% by MRI-PDFF occurred in 57–67% of survodutide-treated patients across the 2.4–6.0 mg dose range versus 14% on placebo — larger relative liver-fat clearance than has been reported for GLP-1 monotherapy at comparable intervention durations.
Appetite and satiety (GLP-1 arm dominant) — The magnitude of weight loss observed in the Phase 2 obesity trial (Le Roux 2024) tracks with GLP-1-mediated appetite suppression and delayed gastric emptying. Survodutide meets or exceeds semaglutide 2.4 mg in Phase 2 weight-loss magnitude at equivalent durations, though no head-to-head trial exists.
Glucose-dependent insulin secretion — Meaningful reductions in HbA1c and fasting glucose in the type 2 diabetes subset, driven by the GLP-1 arm. The glucagon arm introduces a theoretical concern about hyperglycemia, but clinical data indicates that GLP-1-mediated insulinotropic signaling dominates net glycemic effect.
Energy expenditure and thermogenesis — Increased resting energy expenditure differentiates survodutide from GLP-1 monotherapy. Zimmermann et al. (Mol Metab 2022;66:101633) demonstrated in rodent diet-induced obesity that survodutide produced greater body-weight reduction per unit of food-intake suppression than an equally dosed GLP-1 monotherapy — evidence that the glucagon arm contributes an independent expenditure component.
Blood pressure reduction — Post-hoc analysis of the Phase 2 obesity dataset (le Roux, Diabetes Obes Metab 2025) reported dose-dependent reductions in systolic and diastolic blood pressure with survodutide, consistent with the favorable cardiometabolic profile seen across weight-loss agents.
Albumin binding / long half-life — Fatty-acid acylation provides albumin binding that extends terminal half-life to approximately 6 days, supporting once-weekly subcutaneous administration. Steady state is reached over approximately 4–6 weeks of dose escalation.
Hepatic fibrosis modulation — Fibrosis improvement (≥1 stage without MASH worsening) in Phase 2 MASH was 34–36% across active arms versus 22% on placebo. The mechanism is indirect — downstream of sustained hepatic lipid clearance and inflammatory reduction — rather than direct anti-fibrotic receptor signaling.

What the Research Shows

The survodutide evidence base is largely pharmaceutical-sponsored Phase 1 and Phase 2 data, generated on a timeline designed to support regulatory submission. Key studies:

Phase 1 PK/PD (Jungnik et al., Diabetes Obes Metab 2023) — Single- and multiple-ascending-dose studies in healthy volunteers and patients with type 2 diabetes. Established dose-response, safety envelope, and supported once-weekly subcutaneous dosing. Half-life approximately 6 days; roughly linear PK across the therapeutic range.
Phase 2 obesity dose-finding (Le Roux et al., Lancet Diabetes Endocrinol 2024;12(3):162-173) — 387 adults with obesity and without type 2 diabetes randomized to survodutide 0.6, 2.4, 3.6, or 4.8 mg or placebo for 46 weeks. Mean placebo-subtracted weight loss at 46 weeks reached approximately 12.1 percentage points at the 4.8 mg dose (absolute −14.9% vs −2.8% placebo). Gastrointestinal adverse events (nausea, vomiting, diarrhea) were dose-dependent and largely occurred during dose escalation; discontinuation attributable to GI events was meaningful but consistent with class expectations. This study, and Boehringer's broader obesity dataset, support the ~18.7% headline weight-loss number that appears in company communications (adjustable by subpopulation analysis and dose-escalation protocol).
Phase 2 MASH + fibrosis (Sanyal et al., NEJM 2024;391(4):311-319; PMID 38847460) — 293 adults with biopsy-confirmed MASH and F1–F3 fibrosis randomized to survodutide 2.4, 4.8, or 6.0 mg or placebo for 48 weeks (24-week rapid escalation + 24-week maintenance). Primary endpoint — MASH improvement without fibrosis worsening — was achieved in 47%, 62%, and 43% across survodutide arms versus 14% placebo (P<0.001 for quadratic dose-response). MRI-PDFF ≥30% liver-fat decrease: 63%, 67%, 57% survodutide vs 14% placebo. Fibrosis improvement by ≥1 stage: 34%, 36%, 34% vs 22%. Funded by Boehringer Ingelheim; NCT04771273.
Phase 2 type 2 diabetes — Completed Phase 2 studies in T2D showing HbA1c reduction on par with semaglutide at equivalent dose-intensities. Informed Phase 3 T2D program design.
Phase 3 SYNCHRONIZE-1 — Global Phase 3 study in people with obesity and overweight without type 2 diabetes, randomizing to survodutide (up-titrated to 3.6 or 6.0 mg) or placebo for 76 weeks. Baseline characteristics published in PMC12673442. Endpoints: percent body weight change and ≥5% weight reduction from baseline to Week 76.
Phase 3 SYNCHRONIZE-2 — Parallel global Phase 3 study in people with obesity/overweight and type 2 diabetes. Glycemic co-primary endpoints alongside weight outcomes.
Phase 3 SYNCHRONIZE-CVOT — Cardiovascular outcomes trial. Required for broad cardiovascular label if survodutide receives FDA approval for obesity or T2D. Design details disclosed in Boehringer investor materials and clinicaltrials.gov.
Preclinical (Zimmermann et al., Mol Metab 2022;66:101633) — Discovery and preclinical characterization of BI 456906. Demonstrated robust anti-obesity efficacy in diet-induced obese rodents with energy-expenditure and food-intake components both contributing. Informed the human dosing strategy.
Blood pressure post-hoc (le Roux et al., Diabetes Obes Metab 2025) — Post-hoc analysis of the Phase 2 obesity dataset reported dose-dependent improvement in systolic and diastolic blood pressure.

Critical Context — Phase 2 vs Phase 3

Every headline weight-loss and MASH-resolution number for survodutide comes from Phase 2 trials. Phase 2 dose-finding tends to produce optimistic point estimates because dose-selection and enrollment are calibrated to efficacy signal detection. Phase 3 magnitude in obesity drug development has historically equaled or been slightly smaller than Phase 2, with CVOT data adding safety context. Until SYNCHRONIZE-1 / -2 read out, the ~18.7%–19% weight-loss figure cited in sponsor communications should be treated as a best-case signal from an intent-to-treat on-treatment Phase 2 analysis, not a predicted label.

Human Data

Summary of the human evidence base for survodutide:

Phase 1 first-in-human — NCT03591718 and related studies. Single and multiple ascending doses; healthy and T2D participants.
Phase 2 obesity (NCT04667377) — 387 participants, 46 weeks, Le Roux Lancet Diabetes Endocrinol 2024.
Phase 2 MASH (NCT04771273, study 1404-0043) — 293 participants with F1–F3 fibrosis, 48 weeks, Sanyal NEJM 2024 PMID 38847460.
Phase 2 T2D — Completed dose-finding study in participants with type 2 diabetes. HbA1c primary endpoint.
Phase 3 SYNCHRONIZE-1 (NCT06066879) — Obesity without T2D, 76 weeks, survodutide up-titrated to 3.6 or 6.0 mg vs placebo.
Phase 3 SYNCHRONIZE-2 (NCT06066892) — Obesity with T2D, 76 weeks.
Phase 3 SYNCHRONIZE-CVOT — Cardiovascular outcomes, event-driven.
Phase 3 MASH — Being designed on the foundation of the Phase 2 MASH readout. Expected to use biopsy and non-invasive endpoint combinations.
Pharmacokinetics — Half-life ~6 days supporting once-weekly dosing. Steady-state achieved after ~4–6 weeks of dose titration. Linear PK across the therapeutic dose range.

All currently reported data are sponsor-funded; independent replication is limited because the molecule is proprietary and not yet commercially available.

Dosing from the Literature

Dosing below reflects published Phase 2 trial protocols. Survodutide is investigational; no approved dose exists. Self-administration outside an authorized clinical trial or licensed research setting is not advisable.

Trial / Indication	Dose	Route / Frequency	Duration
Phase 2 obesity (Le Roux 2024) — lowest arm	0.6 mg (after escalation)	SubQ once weekly	46 weeks
Phase 2 obesity — mid-dose	2.4 mg	SubQ once weekly	46 weeks
Phase 2 obesity — higher dose	3.6 mg	SubQ once weekly	46 weeks
Phase 2 obesity — highest efficacy arm	4.8 mg	SubQ once weekly	46 weeks
Phase 2 MASH (Sanyal 2024)	2.4, 4.8, or 6.0 mg	SubQ once weekly	48 weeks (24-wk escalation + 24-wk maintenance)
Phase 3 SYNCHRONIZE-1 / -2	Up-titrated to 3.6 or 6.0 mg	SubQ once weekly	76 weeks
Escalation schedule	Stepwise dose escalation	Weekly increments over 20–24 weeks	Gradual to minimize GI intolerance

Dosing Disclaimer

Survodutide dosing schedules were designed with gradual escalation to minimize gastrointestinal adverse effects, which otherwise drive significant discontinuation. The 2.4–4.8 mg range is the Phase 2–validated efficacy range for obesity; 4.8 mg represents the highest Phase 2 dose in both obesity and MASH trials. Dose selection for Phase 3 settled on titration to 3.6 or 6.0 mg. There is no approved prescription pathway as of April 2026; use outside an authorized clinical trial is not medically appropriate.

Reconstitution & Storage

Survodutide is supplied to Phase 2 and Phase 3 trial sites as a sterile pre-formulated subcutaneous solution (single-use or pen-device presentation depending on protocol). A commercial formulation has not been finalized.

Presentation	Concentration	Storage	Use
Trial vial / pen	Variable per protocol dose step	Refrigerate 2–8°C; brief excursions to room temperature per protocol	Single use; discard residual
Research-grade lyophilized (non-clinical)	Reconstitute with BAC water per vial labeling	Freezer for lyophilized; refrigerator for reconstituted	Laboratory research only

Storage — Clinical trial product is refrigerated 2–8°C. Do not freeze the formulated solution. Protect from light. Use within protocol-specified window once dispensed to the participant.
Injection site — Subcutaneous injection in abdomen, thigh, or upper arm. Rotate sites weekly to minimize local reactions.
Needle — 29G–31G half-inch for SubQ. Final commercial device (pen) has not been disclosed.
Inspection — Clear, colorless solution. Discard if cloudy, discolored, or contains visible particulate.
Stability after reconstitution (research-grade) — Defer to vendor specifications; acylated GLP-1/glucagon dual agonists are generally stable refrigerated for 14–28 days when properly reconstituted.

→ Use the Kalios Dosing Calculator for syringe-unit conversions

Side Effects & Risks

Important

Survodutide isn't FDA-approved. Expect GLP-1 GI effects plus glucagon-class cardiovascular and glycemic considerations. This is a doctor conversation before joining a trial or ordering gray-market material.

Survodutide's adverse-event profile in Phase 2 mirrors the GLP-1 / incretin class on the gut side, with glucagon-class cardiovascular and glycemic considerations layered on top.

Gastrointestinal (most common) — Nausea, vomiting, diarrhea, constipation, and dyspepsia. Dose-dependent; largely concentrated in the escalation phase. Discontinuation attributable to GI events was meaningful in Phase 2 obesity (higher than low-dose GLP-1 monotherapy, comparable to aggressive-escalation GLP-1/GIP regimens).
Injection-site reactions — Erythema, pruritus, and mild induration at the injection site. Usually self-limited within 24–48 hours. Rotate sites.
Heart rate elevation — Small mean increases in resting heart rate observed across Phase 2 doses. Consistent with class expectations for GLP-1 and glucagon-class agents.
Glucose considerations — The glucagon arm introduces a theoretical concern about hyperglycemia; in practice, net glycemic effect across the Phase 2 T2D dataset is favorable (HbA1c reduction) because GLP-1-driven insulinotropic signaling dominates. In non-diabetic obesity participants, fasting glucose remained stable or improved.
Gallbladder events — Cholelithiasis and acute cholecystitis have been reported across GLP-1-pathway agents in rapid-weight-loss settings; survodutide is expected to carry similar class signal, with magnitude to be established in Phase 3.
Pancreatitis — Rare cases reported with GLP-1 receptor agonists; survodutide Phase 2 did not surface a disproportionate signal. Remains a class caution.
Thyroid C-cell concerns (class) — Rodent thyroid C-cell hyperplasia has been reported with long-acting GLP-1 receptor agonists; human relevance remains debated. Contraindicated per class guidance in personal or family history of medullary thyroid carcinoma or MEN-2.
Hypoglycemia — Uncommon as monotherapy given GLP-1's glucose-dependent insulin secretion; higher risk when combined with sulfonylureas or insulin.
Fatigue, dizziness, headache — Reported during dose escalation. Typically self-limiting.
Pregnancy and lactation — Contraindicated (class). Effective contraception during treatment and for a wash-out period after discontinuation is advised.
Discontinuation — No taper required pharmacologically. Body weight rebounds gradually over the months following discontinuation in the absence of sustained lifestyle change, per the broader GLP-1-class experience.
Long-term safety — Not yet characterized. SYNCHRONIZE-CVOT will provide the first dedicated long-term cardiovascular dataset. Long-term MASH and fibrosis outcomes remain pending on Phase 3 readout.

Bloodwork & Monitoring

No formal monitoring guideline exists outside the trial protocol. Reasonable monitoring for clinical trial participants or informed research use mirrors the GLP-1 class approach with liver-focused additions given the MASH context:

Baseline CMP and CBC — Liver enzymes (AST/ALT/ALP/bilirubin), renal function (eGFR), electrolytes, CBC.
HbA1c and fasting glucose — Baseline and every 12 weeks. Track glycemic effect; rule out hypoglycemia when combined with sulfonylureas or insulin.
Lipid panel — Baseline and at 12 and 24 weeks. Triglyceride improvement is typical with class agents and with hepatic-fat clearance.
Liver imaging (MASH indication) — Baseline MRI-PDFF or FibroScan; repeat every 6 months during treatment. Liver biopsy as indicated by trial protocol for MASH histology; NIT panels (ELF, FIB-4) for longitudinal monitoring.
Heart rate and blood pressure — Baseline and at each clinic visit. Small HR elevations are expected; substantial rises warrant evaluation.
Thyroid screen — Family/personal MTC/MEN-2 history at baseline (class contraindication). Routine TSH is reasonable.
Pregnancy status — Test at baseline in women of reproductive potential. Counsel on contraception.
Body composition — DEXA at baseline and 6 months for fat/lean mass trajectory — GLP-1 class weight loss preserves less lean mass than protein-forward resistance-training-supported diet loss; baseline gives quantifiable tracking.
Gallbladder symptoms — Low threshold for imaging with right-upper-quadrant pain or post-prandial pain consistent with biliary colic.

Commonly Stacked With

Survodutide is not commercially available, so "stacking" in the conventional sense does not occur. Commentary below is mechanistic — what would be complementary or overlapping if survodutide were clinically available.

Semaglutide

Semaglutide is a GLP-1 monoagonist; survodutide provides overlapping GLP-1 activity plus glucagon agonism. These are alternatives rather than a stack. Sequential use — e.g., semaglutide first for weight-loss initiation, then transition to survodutide for continued weight loss and hepatic-fat clearance — is plausible once survodutide is approved, but has not been studied.

Tirzepatide

Tirzepatide is a GLP-1 / GIP dual agonist. Mechanistically non-overlapping with survodutide's glucagon arm. Phase 3 head-to-head data between survodutide and tirzepatide will determine obesity positioning; survodutide's glucagon arm may be more differentiating in MASH and hepatic-fat-dominant disease than in pure weight-loss efficacy.

Retatrutide

Eli Lilly's triple agonist (GLP-1 / GIP / glucagon). Represents the most direct mechanistic competitor. Head-to-head data are not available; each molecule will establish its positioning through separate Phase 3 programs.

Tesamorelin

GHRH analog for visceral adiposity — FDA-approved in HIV-associated lipodystrophy. Mechanistically orthogonal to survodutide's GLP-1/glucagon action. Theoretical pairing for adiposity-focused metabolic optimization; no controlled combination data.

Resistance training + protein-forward nutrition

Not a drug — but the single highest-leverage companion strategy for any GLP-1-class weight-loss intervention. Rapid appetite suppression plus insufficient protein intake drives disproportionate lean-mass loss; resistance training plus 1.6–2.2 g/kg protein substantially preserves lean mass and improves body-composition outcomes.

→ Check compound compatibility in the Stack Builder

Regulatory Status

Current Status — April 2026

Survodutide (BI 456906) is not approved by the U.S. FDA, the EMA, the UK MHRA, Japan's PMDA, or any other major regulator. It remains an investigational dual GLP-1R/GCGR agonist in coordinated Phase 3 development sponsored by Boehringer Ingelheim in partnership with Zealand Pharma.

The Phase 3 obesity program (SYNCHRONIZE-1 and SYNCHRONIZE-2) enrolled during 2023–2025 with 76-week readout anchors. A dedicated cardiovascular outcomes trial (SYNCHRONIZE-CVOT) is event-driven and ongoing. A Phase 3 MASH program is under design based on the Phase 2 readout (Sanyal NEJM 2024, PMID 38847460). Phase 3 type 2 diabetes studies are in progress.

Survodutide is not specifically named on the WADA Prohibited List. Within-class precedent (semaglutide, tirzepatide) is not uniformly banned; athletes subject to anti-doping testing should seek sport-federation guidance before any use.

Survodutide is not on the FDA Category 2 Bulk Drug Substances peptide list and is therefore not part of HHS Secretary Robert F. Kennedy Jr.'s February 2026 reclassification announcement. As a sponsor-held investigational asset, survodutide's U.S. availability will be determined by Boehringer Ingelheim's forthcoming Biologics License Application rather than by any compounding-rule pathway.

Cost & Access

Survodutide is not approved for human use. It is available through research suppliers for laboratory research purposes only. Patient access occurs only via enrollment in an authorized clinical trial.

Research-chemical channels list survodutide in lyophilized vial formats. Purity, identity, and potency are not guaranteed without independent third-party Certificate of Analysis (HPLC + mass spectrometry). Compounding via 503A or 503B pharmacies is not legally available because survodutide has no reference FDA-approved product and is not on any compoundable bulk-substance list.

Following SYNCHRONIZE-1 / SYNCHRONIZE-2 readouts and a potential Biologics License Application, survodutide would enter the U.S. prescription market under Boehringer Ingelheim's commercialization pathway. Precedent pricing within the GLP-1-class category suggests that launch pricing will be set in the ballpark of other branded weight-loss biologics, with insurance-coverage friction typical of this space. Until approval, no legitimate U.S. prescription pathway exists.

Estimated access situation as of April 2026. Regulatory status changes. Kalios does not sell compounds.

Related Compounds

People researching Survodutide often also look at these:

Pemvidutide

Dual GLP-1 / glucagon receptor agonist with emphasis on MASH (liver fat) alongside weight loss.

Mazdutide

Dual GLP-1 / glucagon receptor agonist developed by Innovent / Eli Lilly, principally for Asian markets.

CagriSema

Fixed-dose combination of cagrilintide + semaglutide. Amylin + GLP-1 obesity protocol.

Next Steps

→ Compare with Mazdutide — another GLP-1/glucagon dual →

→ Try the Peptide Calculator for Survodutide dose math →

→ Ask your provider about SYNCHRONIZE enrollment before chasing gray-market BI 456906 →

Key References

Le 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. Lancet Diabetes Endocrinol. 2024;12(3):162-173. doi:10.1016/S2213-8587(23)00356-X. (Foundational Phase 2 obesity dose-finding; NCT04667377.)
Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, Anstee QM, Hussain SA, Martins EB, Walker M, Oldham P, Starova B, Ogawa W, Wong VW, Ratziu V, Younes R, Hosseini-Tabatabaei A, Loomba R. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024;391(4):311-319. doi:10.1056/NEJMoa2401755. PMID: 38847460. (Phase 2 MASH with fibrosis; NCT04771273.)
Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, Bajrami B, Rist W, Uphues I, Drucker DJ, Klein H, Santhanam R, Hennige AM, Hamilton B, Hennig R, Dux M, Hamprecht B, Bierwisch D, Neubauer H, Tschank G, Stengelin S, Redemann N, Wiedenmann A, Pagler T, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. 2022;66:101633. doi:10.1016/j.molmet.2022.101633.
Jungnik A, Arrubla Martinez J, Plum-Mörschel L, Kapitza C, Lamers D, Thamer C, Unseld A, Hennige AM. Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Diabetes Obes Metab. 2023;25(4):1011-1023. doi:10.1111/dom.14948.
Wharton S, le Roux CW, Kosiborod MN, et al. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE-1 and -2). Obesity (Silver Spring). 2024.
Wharton S, le Roux CW, Kosiborod MN, et al. Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE-1). Diabetes Obes Metab. 2025. PMC12673442.
Le Roux CW, et al. Survodutide, a glucagon receptor/glucagon-like peptide-1 receptor dual agonist, improves blood pressure in adults with obesity: A post hoc analysis from a randomized, placebo-controlled, dose-finding, phase 2 trial. Diabetes Obes Metab. 2025. doi:10.1111/dom.16052.
Loomba R, Hartman ML, Sanyal AJ. Two Trials of Therapeutics for MASH with Liver Fibrosis. Reply. N Engl J Med. 2024;391(15):1462-1463. PMID: 39413388.
Polyzos SA. Two Trials of Therapeutics for MASH with Liver Fibrosis. N Engl J Med. 2024;391(15):1461. PMID: 39413385.
Mei Z, Pu J, Shao Z. Two Trials of Therapeutics for MASH with Liver Fibrosis. N Engl J Med. 2024;391(15):1461-1462. PMID: 39413387.
Boehringer Ingelheim. Phase III studies — survodutide in obesity and overweight. Boehringer Ingelheim corporate press release and investor materials, 2023–2025.
Zealand Pharma A/S. Pipeline and partnerships — BI 456906 / survodutide co-development with Boehringer Ingelheim. zealandpharma.com, 2020–2026.
ClinicalTrials.gov. NCT04667377 (Phase 2 obesity); NCT04771273 (Phase 2 MASH, study 1404-0043); NCT06066879 (SYNCHRONIZE-1); NCT06066892 (SYNCHRONIZE-2).
Tschöp MH, Finan B, Clemmensen C, Gelfanov V, Perez-Tilve D, Müller TD, DiMarchi RD. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab. 2016;24(1):51-62. PMID: 27411008. (Foundational review on multi-receptor agonism rationale including GLP-1/glucagon.)
Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML; Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PMID: 37366315. (For context: closest triple-agonist comparator.)

Last updated: April 2026 | Profile authored by Kalios Peptides research team

Survodutide Phase III