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Study · Non-randomized trial · n = 41 · 2024

9 results

Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis.

Lawitz EJ, Fraessdorf M, Neff GW, Schattenberg JM, Noureddin M, Alkhouri N, Schmid B, Andrews CP, Takács I, Hussain SA, Fenske WK, Gane EJ and 4 more

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Hosseini-Tabatabaei A, Sanyal AJ, Mazo DF, Younes R

Journal of hepatology8 Jun 2024Cited by 51 (Europe PMC)

PMID38857788 (opens in a new tab)DOI10.1016/j.jhep.2024.06.003 (opens in a new tab)PepBankPUB-38857788
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Summary

Background & aimsSurvodutide is a glucagon/glucagon-like peptide-1 receptor dual agonist in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). We investigated the pharmacokinetic and safety profile of survodutide in people with cirrhosis.MethodsThis multinational, non-randomized, open-label, phase I clinical trial initially evaluated a single subcutaneous dose of survodutide 0.3 mg in people with Child-Pugh class A, B or C cirrhosis and healthy individuals with or without overweight/obesity matched for age, sex, and weight; the primary endpoints were the area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) and maximal plasma concentration (Cmax). Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.ResultsIn the single-dose cohorts (n = 41), mean AUC0-∞ and Cmax were similar in those with cirrhosis compared with healthy individuals (90% CIs for adjusted geometric mean ratios spanned 1). Drug-related adverse events occurred in 25.0% of healthy individuals and ≤25.0% of those with cirrhosis after single doses, and 82.4% and 87.5%, respectively, of the multiple-dose cohorts (n = 41) over 28 weeks. Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide treatment.ConclusionsSurvodutide is generally tolerable in people with compensated or decompensated cirrhosis, does not require pharmacokinetic-related dose adjustment, and may improve liver-related non-invasive tests, supporting its investigation for MASH-related cirrhosis.Impact and implicationsSurvodutide is a glucagon receptor/glucagon-like peptide-1 receptor dual agonist in development for treatment of metabolic dysfunction-associated steatohepatitis (MASH), which causes cirrhosis in ∼20% of cases. This trial delineates the pharmacokinetic and safety profile of survodutide in people with compensated or decompensated cirrhosis, and revealed associated reductions in liver fat content, markers of liver fibrosis and body weight. These findings have potential relevance for people with MASH-including those with decompensated cirrhosis, who are usually excluded from clinical trials of investigational drugs. Based on this study, further investigation of survodutide for MASH-related cirrhosis is warranted.ClinicaltrialsGov identifierNCT05296733.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. 9 results from people.

  1. 01HumanNon-randomized trialPharmacokinetics

    After a single 0.3 mg dose, mean AUC0-inf of survodutide was similar in people with cirrhosis and healthy individuals.

    In plain wordsAfter one dose, the amount of survodutide in the blood was similar in people with cirrhosis and in healthy people.

    Peptide
    Survodutide
    Outcome
    No significant changeAUC0-inf after single dose in cirrhosis
    Study

    n = 41

    Comparator
    Healthy individuals
    Analysis
    Primary
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    0.3 mg single dose · subcutaneous · single doseAs given in this study (human).

    Source sentences

    Summary
    In the single-dose cohorts (n = 41), mean AUC0-∞ and Cmax were similar in those with cirrhosis compared with healthy individuals (90% CIs for adjusted geometric mean ratios spanned 1).
    1 context sentence
    Summary · context
    initially evaluated a single subcutaneous dose of survodutide 0.3 mg in people with Child-Pugh class A, B or C cirrhosis and healthy individuals with or without overweight/obesity matched for age, sex, and weight
  2. 02HumanNon-randomized trialPharmacokinetics

    After a single 0.3 mg dose, mean Cmax of survodutide was similar in people with cirrhosis and healthy individuals.

    In plain wordsAfter one dose, peak survodutide levels in the blood were similar in people with cirrhosis and in healthy people.

    Peptide
    Survodutide
    Outcome
    No significant changeCmax after single dose in cirrhosis
    Study

    n = 41

    Comparator
    Healthy individuals
    Analysis
    Primary
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    0.3 mg single dose · subcutaneous · single doseAs given in this study (human).

    Source sentences

    Summary
    In the single-dose cohorts (n = 41), mean AUC0-∞ and Cmax were similar in those with cirrhosis compared with healthy individuals (90% CIs for adjusted geometric mean ratios spanned 1).
    1 context sentence
    Summary · context
    initially evaluated a single subcutaneous dose of survodutide 0.3 mg in people with Child-Pugh class A, B or C cirrhosis and healthy individuals with or without overweight/obesity matched for age, sex, and weight
  3. 03HumanNon-randomized trialSafety outcome

    In multiple-dose cohorts, drug-related adverse events occurred in 82.4% and 87.5% of the two groups, respectively, over 28 weeks.

    In plain wordsWith weekly doses over 28 weeks, drug-related side effects occurred in 82.4% and 87.5% of the two groups.

    Peptide
    Survodutide
    Outcome
    Not applicableDrug-related adverse events over 28 weeks of multiple dosing
    Study

    n = 41

    Analysis
    Primary
    Outcome group
    Adverse events · Whole body
    Studied dose
    0.3 mg escalated to 6.0 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).

    Measurements

    Drug-related AEs
    82.4%
    multiple-dose cohort, first group
    Drug-related AEs
    87.5%
    multiple-dose cohort, second group

    Source sentences

    Summary
    and 82.4% and 87.5%, respectively, of the multiple-dose cohorts (n = 41) over 28 weeks.
    1 context sentence
    Summary · context
    Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.
  4. 04HumanNon-randomized trialEfficacy outcome

    In people with overweight or obesity with or without cirrhosis, liver fat content was generally reduced after 28 weeks of survodutide.

    In plain wordsIn people with overweight or obesity, liver fat was generally lower after 28 weeks of survodutide.

    Peptide
    Survodutide
    Outcome
    DecreaseLiver fat content
    Study

    n = 41

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    0.3 mg escalated to 6.0 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).

    Source sentences

    Summary
    Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide treatment.
    1 context sentence
    Summary · context
    Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.
  5. 05HumanNon-randomized trialEfficacy outcome

    In people with overweight or obesity with or without cirrhosis, liver stiffness was generally reduced after 28 weeks of survodutide.

    In plain wordsIn people with overweight or obesity, liver stiffness was generally lower after 28 weeks of survodutide.

    Peptide
    Survodutide
    Outcome
    DecreaseLiver stiffness
    Study

    n = 41

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    0.3 mg escalated to 6.0 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).

    Source sentences

    Summary
    Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide treatment.
    1 context sentence
    Summary · context
    Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.
  6. 06HumanNon-randomized trialEfficacy outcome

    In people with overweight or obesity with or without cirrhosis, liver volume was generally reduced after 28 weeks of survodutide.

    In plain wordsIn people with overweight or obesity, liver volume was generally lower after 28 weeks of survodutide.

    Peptide
    Survodutide
    Outcome
    DecreaseLiver volume
    Study

    n = 41

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    0.3 mg escalated to 6.0 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).

    Source sentences

    Summary
    Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide treatment.
    1 context sentence
    Summary · context
    Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.
  7. 07HumanNon-randomized trialEfficacy outcome

    In people with overweight or obesity with or without cirrhosis, other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide.

    In plain wordsIn people with overweight or obesity, other liver and metabolic markers were generally lower after 28 weeks of survodutide.

    Peptide
    Survodutide
    Outcome
    DecreaseOther hepatic and metabolic disease markers
    Study

    n = 41

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    0.3 mg escalated to 6.0 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).

    Source sentences

    Summary
    Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide treatment.
    1 context sentence
    Summary · context
    Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.
  8. 08HumanNon-randomized trialEfficacy outcome

    In people with overweight or obesity with or without cirrhosis, body weight was generally reduced after 28 weeks of survodutide.

    In plain wordsIn people with overweight or obesity, body weight was generally lower after 28 weeks of survodutide.

    Peptide
    Survodutide
    Outcome
    DecreaseBody weight
    Study

    n = 41

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.3 mg escalated to 6.0 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).

    Source sentences

    Summary
    Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of survodutide treatment.
    1 context sentence
    Summary · context
    Subsequently, people with overweight/obesity with or without cirrhosis (Child-Pugh class A or B) received once-weekly subcutaneous doses escalated from 0.3 mg to 6.0 mg over 24 weeks then maintained for 4 weeks; the primary endpoint was drug-related treatment-emergent adverse events, with MASH/cirrhosis-related endpoints explored.
  9. 09HumanNon-randomized trialSafety outcome

    After single doses, drug-related adverse events occurred in 25.0% of healthy individuals and up to 25.0% of people with cirrhosis.

    In plain wordsAfter one dose, drug-related side effects occurred in 25.0% of healthy people and up to 25.0% of people with cirrhosis.

    Peptide
    Survodutide
    Outcome
    Not applicableDrug-related adverse events after single dose
    Study

    n: not reported in source

    Comparator
    Healthy individuals
    Outcome group
    Adverse events · Whole body
    Studied dose
    0.3 mg single dose · subcutaneous · single doseAs given in this study (human).

    Measurements

    Drug-related AEs
    25%
    healthy individuals
    Drug-related AEs
    ≤ 25%
    cirrhosis

    Source sentences

    Summary
    Drug-related adverse events occurred in 25.0% of healthy individuals and ≤25.0% of those with cirrhosis after single doses
    1 context sentence
    Summary · context
    initially evaluated a single subcutaneous dose of survodutide 0.3 mg in people with Child-Pugh class A, B or C cirrhosis and healthy individuals with or without overweight/obesity matched for age, sex, and weight

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT05296733

A Study to (1) Compare How BI 456906 is Taken up in the Body of Healthy People and People With Liver Problems and (2) Find Out How People With Overweight and Obesity, With and Without Liver Problems, Tolerate Different Doses of BI 456906

Boehringer Ingelheimn = 8227 Apr 2022 to 29 Dec 2023

Healthy · Liver Diseases · Obesity

Trial pageClinicalTrials.govUpdated 15 Aug 2024

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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