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Survodutide: Dual Agonist Research Overview

Most drugs in the GLP-1 class work by mimicking one gut hormone. Some, like [tirzepatide](/peptides/tirzepatide-dual-gipglp-1-agonist-profile/), combine GLP-1 with GIP. Survodutide takes a different bet entirely.

Most drugs in the GLP-1 class work by mimicking one gut hormone. Some, like tirzepatide, combine GLP-1 with GIP. Survodutide takes a different bet entirely. Developed by Boehringer Ingelheim and Zealand Pharma under the code name BI 456906, survodutide pairs GLP-1 receptor agonism with glucagon receptor agonism -- the hormone that most metabolic drugs try to suppress. The logic: controlled glucagon activation burns liver fat through mechanisms GLP-1 alone cannot reach, while the GLP-1 component handles appetite suppression and blood sugar control. Early clinical data suggests the gamble is paying off, with striking results in both obesity and metabolic dysfunction-associated steatohepatitis (MASH, formerly called NASH).

Table of Contents

Quick Facts

PropertyDetail
Generic nameSurvodutide
Development codeBI 456906
Drug classGlucagon receptor / GLP-1 receptor dual agonist
Structure29-amino acid peptide derived from native glucagon
DevelopersBoehringer Ingelheim and Zealand Pharma
Route of administrationSubcutaneous injection (once weekly)
Half-lifeApproximately 100 hours in humans
Clinical stagePhase 3 (obesity); Phase 2 completed (MASH); Phase 3 MASH planned
FDA designationsFast Track (MASH, 2021); Breakthrough Therapy (MASH, 2024)
EMA designationPRIME scheme (MASH with fibrosis, 2023)
Key indications under studyObesity, overweight, MASH with fibrosis, type 2 diabetes

What Is Survodutide?

Survodutide is an investigational peptide that activates two receptors simultaneously: the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor (GCGR). It is a 29-amino acid synthetic peptide built on the backbone of native glucagon, then chemically modified to gain potent GLP-1 receptor activity while retaining partial glucagon receptor agonism (Zimmerman et al., Molecular Metabolism, 2022).

This dual-receptor approach separates survodutide from the broader GLP-1 agonist family. While drugs like semaglutide and liraglutide target only the GLP-1 receptor, and tirzepatide combines GLP-1 with glucose-dependent insulinotropic polypeptide (GIP), survodutide is one of the few compounds to intentionally harness glucagon -- a hormone traditionally viewed as counterproductive in metabolic disease because it raises blood sugar.

The reasoning behind this design: glucagon does far more than raise glucose. It increases hepatic fatty acid oxidation (fat-burning in the liver), raises energy expenditure, and may directly reduce liver inflammation. When paired with GLP-1's appetite-suppressing and glucose-lowering effects, the combination targets obesity and fatty liver disease from multiple angles.

Co-invented by Boehringer Ingelheim and Zealand Pharma, survodutide sits within Boehringer's cardio-renal-metabolic disease portfolio, a pipeline focused on the connections between heart disease, kidney disease, liver disease, and obesity.

Development History

Survodutide's origins trace back to Zealand Pharma's peptide engineering platform. Zealand specializes in designing peptides with carefully tuned receptor selectivity, and the company partnered with Boehringer Ingelheim to develop a dual glucagon/GLP-1 agonist for metabolic disease.

Key milestones:

  • 2019-2020: Phase 1 studies in healthy volunteers and people with type 2 diabetes established survodutide's pharmacokinetics, confirming a half-life of approximately 100 hours that supports once-weekly dosing (Thomas et al., Diabetes, Obesity and Metabolism, 2024).

  • 2021: Phase 2 trial in type 2 diabetes (NCT04153929) launched, testing survodutide against placebo and open-label semaglutide 1.0 mg. Results published in Diabetologia showed dose-dependent reductions in HbA1c and body weight, with survodutide at the highest dose producing greater weight loss than semaglutide after 16 weeks (Bluher et al., Diabetologia, 2024).

  • May 2021: FDA granted Fast Track Designation for survodutide in MASH with fibrosis.

  • 2022: Phase 2 obesity trial (NCT04667377) in adults with overweight or obesity without diabetes completed enrollment.

  • June 2023: Phase 2 obesity results presented, showing up to 18.7% body weight loss at 46 weeks with the 4.8 mg dose (le Roux et al., The Lancet Diabetes & Endocrinology, 2024).

  • August 2023: Boehringer Ingelheim announced the SYNCHRONIZE Phase 3 program -- five global trials studying survodutide in obesity.

  • November 2023: European Medicines Agency (EMA) accepted survodutide into the PRIME (Priority Medicine) scheme for MASH with fibrosis.

  • February 2024: Phase 2 MASH trial (NCT04771273) top-line results announced -- up to 83% of survodutide-treated adults achieved histological improvement in MASH versus 18.2% on placebo.

  • June 2024: Full Phase 2 MASH data presented at the European Association for the Study of the Liver (EASL) congress and published in the New England Journal of Medicine. Sub-analysis showed up to 64.5% of adults with moderate-to-advanced fibrosis (F2/F3) achieved fibrosis improvement without worsening MASH.

  • October 2024: FDA granted Breakthrough Therapy Designation for survodutide in MASH.

  • 2025-2026: Phase 3 SYNCHRONIZE trials for obesity continue enrolling, with SYNCHRONIZE-1 completion estimated for early 2026. Boehringer announced plans to advance survodutide into a Phase 3 MASH program.

How Survodutide Works: Mechanisms of Action

Survodutide's dual mechanism operates through two distinct receptor pathways that produce complementary metabolic effects.

GLP-1 Receptor Agonism

The GLP-1 receptor arm of survodutide works through the same pathways as established GLP-1 drugs like semaglutide, exenatide, and dulaglutide:

  • Appetite reduction: GLP-1 receptor activation in the hypothalamus and brainstem decreases hunger and increases feelings of fullness after meals.
  • Slowed gastric emptying: Food moves through the stomach more slowly, contributing to prolonged satiety.
  • Glucose-dependent insulin secretion: The GLP-1 pathway stimulates insulin release from pancreatic beta cells, but only when blood glucose is elevated, limiting the risk of hypoglycemia.
  • Glucagon suppression (from GLP-1 side): Paradoxically, GLP-1 signaling in the pancreas suppresses endogenous glucagon secretion from alpha cells. This partially counterbalances the exogenous glucagon agonism from the drug itself. The net effect is a carefully tuned system rather than unchecked glucagon activity.

Glucagon Receptor Agonism

This is what separates survodutide from pure GLP-1 drugs. Glucagon receptor activation produces effects that are especially relevant to liver disease and energy balance:

  • Increased hepatic fatty acid oxidation: Glucagon signals the liver to break down stored fat through beta-oxidation. This is the primary mechanism thought to drive survodutide's striking liver fat reductions. In preclinical models, this effect translates to rapid depletion of liver triglyceride stores (Zimmerman et al., 2022).
  • Elevated energy expenditure: Glucagon increases resting metabolic rate, meaning the body burns more calories even at rest. This partially explains why survodutide produces weight loss beyond what appetite suppression alone would predict.
  • Direct hepatic effects: Beyond fat oxidation, glucagon signaling in the liver may reduce inflammation and modify fibrogenic pathways, potentially contributing to the fibrosis improvements seen in Phase 2 data (Klein et al., Diabetes Research and Clinical Practice, 2024).
  • Amino acid metabolism: Glucagon promotes hepatic amino acid catabolism and urea production.

The Balancing Act

The engineering challenge behind survodutide is getting the ratio right. Too much glucagon agonism raises blood sugar to dangerous levels. Too little, and you lose the liver-specific benefits. The developers solved this by designing a peptide with full GLP-1 receptor activation paired with partial glucagon receptor activation. The GLP-1 component's insulin-stimulating and endogenous-glucagon-suppressing effects offset the hyperglycemic tendency of exogenous glucagon agonism.

In the Phase 2 type 2 diabetes trial, survodutide actually lowered HbA1c by up to 1.5 percentage points while simultaneously activating glucagon receptors, confirming that the balance works in clinical practice (Bluher et al., 2024).

Clinical Research

Phase 2: Type 2 Diabetes (NCT04153929)

This randomized, double-blind trial tested five survodutide doses (0.3 mg to 4.8 mg weekly) against placebo and open-label semaglutide 1.0 mg in 411 adults with type 2 diabetes over 16 weeks of treatment.

Key results:

  • HbA1c reductions were dose-dependent, reaching up to -1.5% at the 4.8 mg dose versus -0.4% with placebo.
  • Body weight loss at 4.8 mg reached approximately -8.7% versus -2.8% with semaglutide 1.0 mg at 16 weeks.
  • The trial had no direct statistical comparison powered for survodutide vs. semaglutide (the semaglutide arm was open-label), but the numerical difference was notable.
  • GI adverse events were the most common side effects, reported in 50% of survodutide-treated participants.

Published: Bluher et al., Diabetologia, 2024

Phase 2: Obesity Without Diabetes (NCT04667377)

A randomized, double-blind, placebo-controlled trial enrolled 387 adults with a BMI of 27 or higher (without type 2 diabetes). Participants received survodutide at doses of 0.6 mg, 2.4 mg, 3.6 mg, or 4.8 mg weekly, or placebo, for 46 weeks.

Key results:

  • At the 4.8 mg dose, participants lost an average of 14.9% of body weight from baseline at 46 weeks. The top-performing subgroup reached up to 18.7% weight loss.
  • Dose-response was clear: the 2.4 mg dose produced ~10% weight loss, the 3.6 mg dose ~13%, and the 4.8 mg dose ~15%.
  • 83% of participants on 4.8 mg achieved at least 5% body weight loss, 69% achieved at least 10%, and 55% achieved at least 15%.
  • Placebo group lost approximately 2.8%.

Published: le Roux et al., The Lancet Diabetes & Endocrinology, 2024

Phase 2: MASH with Fibrosis (NCT04771273)

This was the trial that put survodutide on the map for liver disease. A randomized, double-blind, placebo-controlled study enrolled 295 adults with biopsy-confirmed MASH and fibrosis stages F1, F2, or F3. Participants received survodutide 2.4 mg, 4.8 mg, or 6.0 mg weekly, or placebo, for 48 weeks.

Primary endpoint (MASH improvement without worsening fibrosis):

  • Survodutide 2.4 mg: 47.2%
  • Survodutide 4.8 mg: 62.1%
  • Survodutide 6.0 mg: 83.0%
  • Placebo: 18.2%
  • The response difference for the 6.0 mg group vs. placebo was 64.8 percentage points (p<0.0001).

Liver fat reduction (at least 30% relative reduction):

  • Up to 87.0% of survodutide-treated adults achieved at least a 30% relative reduction in liver fat versus 19.7% on placebo.

Fibrosis improvement (at least one stage decrease):

  • Up to 52.3% of all survodutide-treated adults (F1-F3) achieved fibrosis improvement.
  • In a sub-analysis of patients with more severe fibrosis (F2 and F3 only), up to 64.5% achieved fibrosis improvement without worsening MASH.

These results were published in the New England Journal of Medicine in June 2024 and presented at EASL.

Published: Sanyal et al., NEJM, 2024

Phase 1: Cirrhosis Study (NCT05296733)

Boehringer Ingelheim is also running a two-part Phase 1 trial in people with cirrhosis (F4 fibrosis) and varying degrees of liver dysfunction. Part 1 examines how cirrhosis affects survodutide pharmacokinetics. Part 2 tests tolerability of survodutide in people with overweight or obesity who also have cirrhosis.

Results from Part 1, published in the Journal of Hepatology, showed that survodutide exposure was higher in cirrhotic patients compared to healthy controls, but the drug was generally tolerable (Lawitz et al., Journal of Hepatology, 2024).

Phase 3: The SYNCHRONIZE Program

Boehringer Ingelheim launched the SYNCHRONIZE program in late 2023, consisting of five Phase 3 trials for obesity:

TrialPopulationKey Feature
SYNCHRONIZE-1 (NCT06066515)Adults with obesity/overweight, no diabetesPrimary weight loss efficacy trial
SYNCHRONIZE-2 (NCT06066528)Adults with obesity/overweight plus type 2 diabetesWeight loss + glycemic control
SYNCHRONIZE-CVOT (NCT06077864)Adults with obesity/overweight + CV disease, CKD, or CV risk factorsCardiovascular outcomes trial
SYNCHRONIZE-JP (NCT06176365)Japanese adults with obesityRegional trial
SYNCHRONIZE-CN (NCT06214741)Chinese adults with overweight/obesityRegional trial

SYNCHRONIZE-1 is estimated to complete in early 2026. Both the Japan and China trials include liver fat reduction (measured by MRI) as a key secondary endpoint, reflecting survodutide's potential dual benefit for weight and liver health.

Boehringer has also announced plans to initiate a Phase 3 MASH trial, though specific design details have not been publicly disclosed as of early 2026.

Administration and Dosing

Survodutide is administered as a once-weekly subcutaneous injection. The long half-life of approximately 100 hours supports this dosing schedule.

In clinical trials, survodutide follows a dose-escalation protocol to reduce gastrointestinal side effects:

Phase 2 obesity trial escalation schedule (approximate):

  • Weeks 1-4: Starting dose (0.3-0.6 mg)
  • Doses escalated every 4 weeks
  • Target maintenance doses: 2.4 mg, 4.8 mg, or 6.0 mg weekly
  • Total escalation period: up to 20-24 weeks
  • Maintenance period: remaining trial duration at target dose

The Phase 2 MASH trial used a similar approach, escalating to 2.4 mg, 4.8 mg, or 6.0 mg over up to 24 weeks, then maintaining the target dose for 24 weeks.

Important note: Survodutide is not yet approved anywhere in the world. These dosing details come from clinical trial protocols and should not be interpreted as prescribing information. The final approved dosing regimen, if the drug is approved, may differ from what was used in trials.

Safety Profile and Side Effects

Survodutide's safety data comes from Phase 1 and Phase 2 trials. The overall profile is consistent with the GLP-1 drug class, with gastrointestinal symptoms accounting for most reported problems.

Most Common Side Effects

In the Phase 2 trials, GI events were reported in approximately 50-56% of participants receiving survodutide:

  • Nausea: The most frequent adverse event, reported in 33-56% of survodutide groups depending on dose (versus ~15% with placebo). Most episodes were mild to moderate and occurred during the dose-escalation phase.
  • Vomiting: Reported in approximately 12-20% of participants.
  • Diarrhea: Reported in approximately 15-25% of participants.
  • Decreased appetite: Common but expected given the mechanism of action.
  • Constipation and dyspepsia: Less frequent but reported across dose groups.

Discontinuation Rates

In the Phase 2 obesity trial, the discontinuation rate due to adverse events was approximately 24.6% across survodutide dose groups, notably higher than the 5% rate seen in the placebo group. This is a meaningful concern and a number that Phase 3 trials will need to address. By comparison, Phase 3 trials of semaglutide 2.4 mg (Wegovy) reported discontinuation rates of approximately 7% due to adverse events.

In the MASH trial, transient elevations in liver enzymes (ALT, AST) were observed in some survodutide-treated participants. Researchers attributed this to the drug's effects on hepatic fat metabolism rather than liver toxicity -- as liver fat decreases rapidly, transaminase levels can temporarily spike before normalizing. Boehringer Ingelheim reported that treatment with survodutide "did not show unexpected safety or tolerability issues, including at the higher dose of 6.0 mg."

Cardiovascular Observations

Moderate increases in heart rate have been observed with dual GCGR/GLP-1R agonism, consistent with the known cardiovascular effects of GLP-1 receptor agonists. The SYNCHRONIZE-CVOT trial is specifically designed to evaluate cardiovascular outcomes.

What Is Not Yet Known

Phase 2 trials are not large enough to detect rare adverse events. Long-term safety data beyond 48 weeks, thyroid-related effects (a theoretical concern with GLP-1 agonists), and outcomes in patients with more severe organ impairment will require Phase 3 and post-marketing data.

Comparisons with Other Multi-Agonists

The multi-agonist space has become one of the most competitive areas in metabolic drug development. Alongside injectable multi-agonists, oral GLP-1 approaches like orforglipron are also advancing through late-stage trials. Understanding where survodutide fits requires comparing its receptor targets, clinical data, and therapeutic focus to other combination approaches.

Survodutide vs. Tirzepatide (Mounjaro/Zepbound)

Tirzepatide is a GIP/GLP-1 dual agonist -- it activates a completely different second receptor than survodutide. GIP (glucose-dependent insulinotropic polypeptide) primarily improves insulin sensitivity and glucose handling.

FeatureSurvodutideTirzepatide
Receptor targetsGlucagon + GLP-1GIP + GLP-1
Approved?No (investigational)Yes (obesity + T2D)
Phase 2 weight lossUp to 18.7% at 46 weeksUp to 22.5% at 72 weeks (SURMOUNT-1)
Liver-specific benefitStrong evidence (87% liver fat reduction)Some evidence (studied in MASLD)
Primary strengthLiver fat/fibrosis + weight lossWeight loss + glucose control

Tirzepatide has the advantage of being approved and available. Survodutide's glucagon component may give it an edge in liver disease specifically, because glucagon directly increases hepatic fat oxidation -- a mechanism GIP does not share.

Survodutide vs. Retatrutide

Retatrutide (Eli Lilly) is a triple agonist targeting GIP, GLP-1, and glucagon receptors simultaneously. It produced up to 24.2% weight loss at 48 weeks in Phase 2 data. By including all three targets, retatrutide may capture the liver benefits of glucagon agonism (like survodutide) and the metabolic benefits of GIP (like tirzepatide).

Retatrutide is the most pharmacologically complex of these agents. Its Phase 3 trials are ongoing. Whether having three targets is better than two remains an open question -- more targets can mean more side effects as well as more efficacy.

Survodutide vs. Pemvidutide

Pemvidutide (Altimmune) is another glucagon/GLP-1 dual agonist, making it the most direct comparison to survodutide. Both drugs share the same receptor targets. Pemvidutide showed approximately 10-15% weight loss in Phase 2 at 48 weeks and is being studied in MASH. Survodutide's Phase 2 weight loss (up to 18.7%) and MASH efficacy (up to 83% improvement) numerically exceed pemvidutide's published data, though direct comparison across separate trials requires caution.

Survodutide vs. CagriSema

CagriSema (Novo Nordisk) combines semaglutide with cagrilintide (an amylin analog) in a single injection. It targets different pathways -- amylin receptor agonism for appetite suppression rather than glucagon agonism for liver fat. CagriSema produced up to 22.7% weight loss in Phase 3 (REDEFINE 1). The approach is more weight-loss focused and less liver-disease focused than survodutide.

As of early 2026, survodutide is not approved for any indication in any country. It remains an investigational drug available only through clinical trials.

Regulatory designations received:

  • FDA Fast Track Designation (May 2021): For treatment of MASH with fibrosis.
  • EMA PRIME Scheme (November 2023): For MASH with fibrosis.
  • FDA Breakthrough Therapy Designation (October 2024): For MASH. This designation, granted after the Phase 2 NEJM publication, provides more intensive FDA guidance and the possibility of rolling review to accelerate approval.

Estimated timeline: The Phase 3 SYNCHRONIZE-1 obesity trial is expected to read out in early 2026. If results are positive, Boehringer Ingelheim could file for regulatory approval in obesity by late 2026 or 2027. The MASH timeline depends on Phase 3 trial initiation and completion.

Research compound availability: Survodutide is not legally available outside of clinical trials. It has no brand name yet. Unlike research peptides such as BPC-157 or AOD-9604 that circulate in the gray market, survodutide is a pharmaceutical-grade compound under active Phase 3 development. Any products sold online as survodutide are research chemicals not manufactured under GMP standards and not intended for human use.

Frequently Asked Questions

How is survodutide different from semaglutide (Ozempic/Wegovy)?

Semaglutide targets only the GLP-1 receptor. Survodutide targets both the GLP-1 and glucagon receptors. The glucagon component gives survodutide a direct fat-burning effect in the liver that semaglutide lacks. In a 16-week Phase 2 comparison, survodutide produced numerically greater weight loss than semaglutide 1.0 mg, though the trial was not powered for head-to-head statistical comparison.

Can survodutide treat fatty liver disease?

In a Phase 2 trial of 295 adults with MASH (the progressive, inflammatory form of fatty liver disease), survodutide at the 6.0 mg dose produced histological improvement in 83% of patients versus 18.2% on placebo, with up to 87% achieving at least a 30% reduction in liver fat content (Sanyal et al., NEJM, 2024). The drug also received FDA Breakthrough Therapy Designation for MASH. Phase 3 MASH trials are planned.

When will survodutide be available?

Survodutide has not been approved by any regulatory agency. Phase 3 obesity trials are expected to read out in 2026. If results are positive and regulatory review goes smoothly, the earliest commercial availability for obesity would likely be late 2027 or 2028. A MASH approval could follow on a separate timeline.

What are the main side effects of survodutide?

Gastrointestinal symptoms are the most common: nausea (33-56%), vomiting (12-20%), and diarrhea (15-25%). These side effects typically peak during the dose-escalation phase and improve over time. The discontinuation rate in Phase 2 was approximately 25%, which is higher than most approved GLP-1 drugs and something Phase 3 trials will need to address.

How does survodutide compare to tirzepatide for weight loss?

In Phase 2 trials, survodutide produced up to 18.7% weight loss at 46 weeks, while tirzepatide produced up to 22.5% at 72 weeks in its Phase 3 program. The trials had different designs, durations, and populations, so direct comparison is not straightforward. Survodutide's glucagon component may offer stronger liver-specific benefits, making it potentially more useful for patients with both obesity and liver disease.

Why include glucagon in a metabolic drug if glucagon raises blood sugar?

The design is counterintuitive but deliberate. While glucagon raises blood glucose, the GLP-1 component in survodutide stimulates insulin release and suppresses endogenous glucagon secretion from the pancreas. This creates a net balance where blood sugar stays controlled (survodutide actually lowered HbA1c in diabetes trials) while patients gain the liver-fat-burning and energy-expenditure benefits of glucagon receptor activation.

Is survodutide the same as pemvidutide?

No. Pemvidutide (Altimmune) is a different drug that shares the same dual glucagon/GLP-1 mechanism. While both target the same receptors, they are structurally distinct peptides with different potency ratios, pharmacokinetics, and clinical data. Survodutide has shown numerically stronger results in both weight loss and MASH in Phase 2 trials.

The Bottom Line

Survodutide is one of the more scientifically interesting compounds in the metabolic drug pipeline. By adding glucagon agonism to a GLP-1 backbone, it directly addresses liver fat accumulation -- a problem that pure GLP-1 drugs can improve but not as aggressively. The Phase 2 MASH results, with 83% of patients on the high dose showing histological improvement and up to 87% achieving meaningful liver fat reduction, are among the strongest published for any drug in that space.

The weight loss numbers are solid, too. Up to 18.7% body weight reduction at 46 weeks puts survodutide in the same general range as other next-generation obesity drugs, though not quite matching the top-line figures from tirzepatide or retatrutide.

The open question is tolerability. A 25% discontinuation rate in Phase 2 is high and could limit real-world adoption if Phase 3 does not improve on it. GI side effects -- particularly nausea -- appear more common with survodutide than with most approved GLP-1 drugs. Whether optimized dose-escalation protocols in Phase 3 can reduce these numbers will be a defining factor in the drug's commercial potential.

If the SYNCHRONIZE Phase 3 trials confirm Phase 2 efficacy with an acceptable safety profile, survodutide could become the first approved glucagon/GLP-1 dual agonist and potentially the preferred option for the substantial overlap population of people living with both obesity and fatty liver disease. The FDA's Breakthrough Therapy and Fast Track designations signal that regulators see the same potential. But Phase 2 promise does not always survive Phase 3 scrutiny -- and that is where survodutide's story currently stands.

This article is for educational purposes only and does not constitute medical advice. Survodutide is an investigational drug not approved for any indication. Always consult a qualified healthcare provider before making decisions about medications or treatments.

Last updated: February 2026

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