reptides / survodutide

survodutide

In a 2026 phase 3 obesity trial, mean weight loss at 76 weeks reached 13.0% with survodutide versus 5.4% with placebo. An earlier biopsy-based MASH trial also found histologic improvement. Survodutide remains investigational, and neither trial included an active incretin comparator.

GLP-1 and glucagon receptor dual agonist

  • Once-weekly investigational peptide
  • Activates GLP-1 and glucagon receptors
  • Studied separately in obesity and liver disease programs
Is it approved? What did phase 3 show? What changed in MASH? What safety findings mattered? How does it compare? What does glucagon add?

Is survodutide approved?

Survodutide remains investigational in the United States. FDA designations and phase 3 enrollment can speed or structure development, but they are not marketing approval.

No exact-name survodutide approval appears in FDA approval data.

US approval status

US approval status

Drugs@FDA and openFDA.

No exact-name FDA approval record matches survodutide.

Read the original source

What did SYNCHRONIZE-1 report in obesity?

In a 725-person phase 3 trial of adults without diabetes, mean week-76 weight change under the treatment-regimen estimand was -12.2% with 3.6 mg, -13.0% with 6.0 mg, and -5.4% with placebo. Gastrointestinal symptoms occurred in 80.9%, 89.7%, and 47.9%, respectively.

The earlier 16.6% figure came from an efficacy analysis that assumed continued treatment. The treatment-regimen estimates include outcomes after discontinuation, rescue treatment, and prolonged dose escalation.

SYNCHRONIZE-1 · phase 3 obesity

Randomized trial

New England Journal of Medicine, 2026

In 725 adults, week-76 treatment-regimen mean weight change was -12.2% at 3.6 mg and -13.0% at 6.0 mg versus -5.4% with placebo; gastrointestinal symptoms were common.

Participants / model
Adults with BMI at least 30, or at least 27 plus a complication, without diabetes
Treatment
Weekly survodutide 3.6 mg, 6.0 mg, or placebo
Follow-up
76 weeks
Study design
Randomized, double-blind phase 3 trial

The result does not provide a head-to-head comparison with another active obesity medicine.

Read the original source

What did the biopsy-based MASH trial actually measure?

At 48 weeks, MASH improvement without worsening fibrosis occurred in 47%, 62%, and 43% across the three survodutide doses versus 14% with placebo. At least one-stage fibrosis improvement without worsening MASH occurred in 34%, 36%, and 34% versus 22%. The fibrosis comparison was not clearly established by those numerical differences.

These are biopsy endpoints in participants with F1 to F3 fibrosis. They do not yet show fewer cirrhosis complications, transplants, cardiovascular events, or deaths.

Survodutide phase 2 · biopsy outcomes

Randomized trial

Sanyal et al., New England Journal of Medicine, 2024

MASH improvement without worsening fibrosis was more frequent with survodutide; fibrosis improvement values were numerically closer to placebo.

Participants / model
Adults with biopsy-confirmed MASH and F1 to F3 fibrosis
Treatment
Weekly survodutide at three doses or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind phase 2 trial

Biopsy surrogates do not establish reduced liver-related clinical events.

Read the original source

What adverse effects appeared in the obesity and MASH trials?

In SYNCHRONIZE-1, gastrointestinal symptoms occurred in 80.9% with 3.6 mg, 89.7% with 6.0 mg, and 47.9% with placebo; the published abstract reported no deaths. In the 48-week MASH trial, nausea occurred in 66% across survodutide groups versus 23% with placebo, diarrhea in 49% versus 23%, vomiting in 41% versus 4%, and serious adverse events in 8% versus 7%.

The abstracts do not report regimen-specific discontinuation counts for every trial arm, so they cannot show precisely how often adverse effects ended treatment.

SYNCHRONIZE-1 · phase 3 obesity

Randomized trial

New England Journal of Medicine, 2026

In 725 adults, week-76 treatment-regimen mean weight change was -12.2% at 3.6 mg and -13.0% at 6.0 mg versus -5.4% with placebo; gastrointestinal symptoms were common.

Participants / model
Adults with BMI at least 30, or at least 27 plus a complication, without diabetes
Treatment
Weekly survodutide 3.6 mg, 6.0 mg, or placebo
Follow-up
76 weeks
Study design
Randomized, double-blind phase 3 trial

The result does not provide a head-to-head comparison with another active obesity medicine.

Read the original source
Survodutide phase 2 · biopsy outcomes

Randomized trial

Sanyal et al., New England Journal of Medicine, 2024

MASH improvement without worsening fibrosis was more frequent with survodutide; fibrosis improvement values were numerically closer to placebo.

Participants / model
Adults with biopsy-confirmed MASH and F1 to F3 fibrosis
Treatment
Weekly survodutide at three doses or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind phase 2 trial

Biopsy surrogates do not establish reduced liver-related clinical events.

Read the original source

Has survodutide been directly compared with tirzepatide or semaglutide?

The phase 3 obesity report provides no head-to-head randomized outcome against those treatments. Comparing percentages across separate trials does not control population, estimand, duration, dose escalation, or missing-data handling.

SYNCHRONIZE-1 · phase 3 obesity

Randomized trial

New England Journal of Medicine, 2026

In 725 adults, week-76 treatment-regimen mean weight change was -12.2% at 3.6 mg and -13.0% at 6.0 mg versus -5.4% with placebo; gastrointestinal symptoms were common.

Participants / model
Adults with BMI at least 30, or at least 27 plus a complication, without diabetes
Treatment
Weekly survodutide 3.6 mg, 6.0 mg, or placebo
Follow-up
76 weeks
Study design
Randomized, double-blind phase 3 trial

The result does not provide a head-to-head comparison with another active obesity medicine.

Read the original source

Does the glucagon arm prove higher energy expenditure or liver-fat oxidation in people?

The dual-receptor design is established, and human trials show weight and liver changes. The trials do not isolate glucagon receptor activity or measure a fixed increase in resting metabolic rate.

SYNCHRONIZE-1 · phase 3 obesity

Randomized trial

New England Journal of Medicine, 2026

In 725 adults, week-76 treatment-regimen mean weight change was -12.2% at 3.6 mg and -13.0% at 6.0 mg versus -5.4% with placebo; gastrointestinal symptoms were common.

Participants / model
Adults with BMI at least 30, or at least 27 plus a complication, without diabetes
Treatment
Weekly survodutide 3.6 mg, 6.0 mg, or placebo
Follow-up
76 weeks
Study design
Randomized, double-blind phase 3 trial

The result does not provide a head-to-head comparison with another active obesity medicine.

Read the original source
Survodutide phase 2 · biopsy outcomes

Randomized trial

Sanyal et al., New England Journal of Medicine, 2024

MASH improvement without worsening fibrosis was more frequent with survodutide; fibrosis improvement values were numerically closer to placebo.

Participants / model
Adults with biopsy-confirmed MASH and F1 to F3 fibrosis
Treatment
Weekly survodutide at three doses or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind phase 2 trial

Biopsy surrogates do not establish reduced liver-related clinical events.

Read the original source

Studies and sources

US approval status

US approval status

Drugs@FDA and openFDA.

No exact-name FDA approval record matches survodutide.

Read the original source
SYNCHRONIZE-1 · phase 3 obesity

Randomized trial

New England Journal of Medicine, 2026

In 725 adults, week-76 treatment-regimen mean weight change was -12.2% at 3.6 mg and -13.0% at 6.0 mg versus -5.4% with placebo; gastrointestinal symptoms were common.

Participants / model
Adults with BMI at least 30, or at least 27 plus a complication, without diabetes
Treatment
Weekly survodutide 3.6 mg, 6.0 mg, or placebo
Follow-up
76 weeks
Study design
Randomized, double-blind phase 3 trial

The result does not provide a head-to-head comparison with another active obesity medicine.

Read the original source
Survodutide phase 2 · biopsy outcomes

Randomized trial

Sanyal et al., New England Journal of Medicine, 2024

MASH improvement without worsening fibrosis was more frequent with survodutide; fibrosis improvement values were numerically closer to placebo.

Participants / model
Adults with biopsy-confirmed MASH and F1 to F3 fibrosis
Treatment
Weekly survodutide at three doses or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind phase 2 trial

Biopsy surrogates do not establish reduced liver-related clinical events.

Read the original source

Why is survodutide in A tier?

The A tier reflects randomized phase 3 obesity data and biopsy-based MASH evidence. Survodutide is not approved, has not been compared head to head with tirzepatide, and has not been shown to reduce liver-related clinical events.

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