Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906.

Jungnik A, Arrubla Martinez J, Plum-Mörschel L, Kapitza C, Lamers D, Thamer C, Schölch C, Desch M, Hennige AM

Diabetes, obesity & metabolism30 Jan 2023Cited by 55 (Europe PMC)

PMID36527386DOI10.1111/dom.14948PepBankPUB-36527386

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC. Results still quote short attributed sentences.

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanNon-randomized trialSafety outcome
In multiple rising dose Part A, 10 subjects (12.5%) discontinued BI 456906.
In plain wordsIn a 6-week multiple-dose study, 10 of 80 people stopped BI 456906.
Peptide
Survodutide
Outcome
Not applicableDiscontinuation of BI 456906 in multiple rising dose Part A
Study
n = 80
Outcome group
Adverse events · Pharmacology
Studied dose
Dose not stated · subcutaneous · 6 weeksAs given in this study (human).
Measurements
Discontinuations
10 subjects
Part A
Discontinuations
12.5%
Part A
Source sentences
Summary
During MRD Part A (N = 80), 10 subjects (12.5%)
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m² .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738609
02HumanNon-randomized trialSafety outcome
In multiple rising dose Part A, the most common reason for discontinuing BI 456906 was a cardiac or vascular adverse event (n = 6, 7.5%).
In plain wordsIn a 6-week multiple-dose study, six people stopped BI 456906 because of a heart or blood vessel side effect.
Peptide
Survodutide
Outcome
Not applicableDiscontinuation due to cardiac or vascular adverse events in Part A
Study
n = 80
Outcome group
Adverse events · Cardiovascular
Studied dose
Dose not stated · subcutaneous · 6 weeksAs given in this study (human).
Measurements
Discontinuations due to cardiac or vascular AE
6 subjects
Part A
Discontinuations due to cardiac or vascular AE
7.5%
Part A
Source sentences
Summary
During MRD Part A (N = 80), 10 subjects (12.5%) discontinued BI 456906, most commonly because of a cardiac or vascular AE (n = 6, 7.5%)
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m² .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738610
03HumanNon-randomized trialSafety outcome
In multiple rising dose Part B, eight subjects (17.8%) discontinued BI 456906.
In plain wordsIn a 16-week multiple-dose study, eight of 45 people stopped BI 456906.
Peptide
Survodutide
Outcome
Not applicableDiscontinuation of BI 456906 in multiple rising dose Part B
Study
n = 45
Outcome group
Adverse events · Pharmacology
Studied dose
Dose not stated · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Discontinuations
17.8%
Part B
Source sentences
Summary
during Part B (N = 45), eight subjects (17.8%)
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m² .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738611
04HumanNon-randomized trialSafety outcome
In multiple rising dose Part B, six subjects (13.3%) discontinued BI 456906 because of adverse events, most commonly gastrointestinal disorders.
In plain wordsIn a 16-week multiple-dose study, six people stopped BI 456906 because of side effects, mostly stomach and gut problems.
Peptide
Survodutide
Outcome
Not applicableDiscontinuation due to adverse events in Part B
Study
n = 45
Outcome group
Adverse events · Gastrointestinal
Studied dose
Dose not stated · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Discontinuations due to AEs
6 subjects
Part B
Discontinuations due to AEs
13.3%
Part B
Source sentences
Summary
during Part B (N = 45), eight subjects (17.8%) discontinued BI 456906, mainly because of AEs (n = 6, 13.3%), most commonly gastrointestinal disorders.
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m² .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738612
05HumanNon-randomized trialEfficacy outcome
In the single rising dose study in males with BMI 20 to under 30, mean body weight decreased with increasing BI 456906 dose.
In plain wordsIn men in a single-dose study, body weight fell as the BI 456906 dose went up.
Peptide
Survodutide
Outcome
DecreaseBody weight in single rising dose study
Study
n = 24
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
In the SRD study (N = 24), mean body weight decreased with increasing BI 456906 dose.
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ia study (NCT03175211) investigated single rising doses (SRDs) of BI 456906 in 24 males with a body mass index (BMI) of 20-2 .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738601
06HumanNon-randomized trialSafety outcome
In the single rising dose study, decreased appetite was the most frequent drug-related adverse event (n = 9, 50.0%).
In plain wordsIn men in a single-dose study, reduced appetite was the most common drug-related side effect of BI 456906.
Peptide
Survodutide
Outcome
Not applicableDecreased appetite in single rising dose study
Study
n = 24
Outcome group
Adverse events · Pharmacology
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
Decreased appetite
9 participants
SRD
Decreased appetite
50%
SRD
Source sentences
Summary
The most frequent drug-related AE with SRDs was decreased appetite (n = 9, 50.0%)
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ia study (NCT03175211) investigated single rising doses (SRDs) of BI 456906 in 24 males with a body mass index (BMI) of 20-2 .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738607
07HumanNon-randomized trialSafety outcome
In the single rising dose study, two subjects (8.3%) did not complete the trial because of adverse events (nausea and vomiting).
In plain wordsIn men in a single-dose study, two people did not finish because of nausea and vomiting.
Peptide
Survodutide
Outcome
Not applicableDiscontinuation due to adverse events in single rising dose study
Study
n = 24
Outcome group
Adverse events · Pharmacology
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
Non-completion due to adverse events
2 subjects
SRD
Non-completion due to adverse events
8.3%
SRD
Source sentences
Summary
and two subjects (8.3%) did not complete the trial because of AEs (nausea and vomiting).
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ia study (NCT03175211) investigated single rising doses (SRDs) of BI 456906 in 24 males with a body mass index (BMI) of 20-2 .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738608
08HumanNon-randomized trialEfficacy outcome
In adults with BMI 27-40 in multiple rising dose Part A, the maximum decrease in placebo-corrected mean body weight was 5.79% at week 6 (dosage schedule 1).
In plain wordsIn adults with overweight or obesity, BI 456906 lowered body weight by up to 5.79% more than placebo after 6 weeks.
Peptide
Survodutide
Outcome
DecreasePlacebo-corrected body weight change at week 6 (Part A)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
dosage schedule 1 · subcutaneous · 6 weeksAs given in this study (human).
Measurements
Placebo-corrected body weight change
−5.79%
DS1, week 6
Source sentences
Summary
In the MRD study, the maximum decreases in placebo-corrected mean body weight were at week 6 (-5.79%, dosage schedule [DS] 1; Part A)
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m² .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738602
09HumanNon-randomized trialEfficacy outcome
In adults with BMI 27-40 in multiple rising dose Part B, the maximum decrease in placebo-corrected mean body weight was 13.8% at week 16 (dosage schedule 7).
In plain wordsIn adults with overweight or obesity, BI 456906 lowered body weight by up to 13.8% more than placebo after 16 weeks.
Peptide
Survodutide
Outcome
DecreasePlacebo-corrected body weight change at week 16 (Part B)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
dosage schedule 7 · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Placebo-corrected body weight change
−13.8%
DS7, week 16
Source sentences
Summary
week 16 (-13.8%, DS7; Part B).
2 context sentences(design, population, supporting numbers)
Summary · context
A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m² .
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738603
10HumanNon-randomized trialMechanism
BI 456906 reduced plasma amino acids, which indicates target engagement at GCGRs and GLP-1Rs.
In plain wordsIn people given BI 456906, blood amino acids fell, which suggests the drug acts on its target receptors.
Peptide
Survodutide
Outcome
DecreasePlasma amino acids
Study
n: not reported in source
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
BI 456906 reduced plasma amino acids and glucagon, indicating target engagement at GCGRs and GLP-1Rs.
1 context sentence(design, population, supporting numbers)
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738604
11HumanNon-randomized trialMechanism
BI 456906 reduced plasma glucagon, which indicates target engagement at GCGRs and GLP-1Rs.
In plain wordsIn people given BI 456906, blood glucagon fell, which suggests the drug acts on its target receptors.
Peptide
Survodutide
Outcome
DecreasePlasma glucagon
Study
n: not reported in source
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
BI 456906 reduced plasma amino acids and glucagon, indicating target engagement at GCGRs and GLP-1Rs.
1 context sentence(design, population, supporting numbers)
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738605
12HumanNon-randomized trialSafety outcome
Drug-related adverse events increased with BI 456906 dose.
In plain wordsIn people given BI 456906, drug-related side effects became more frequent as the dose went up.
Peptide
Survodutide
Outcome
IncreaseDrug-related adverse events by dose
Study
n: not reported in source
Outcome group
Adverse events · Pharmacology
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
Drug-related adverse events (AEs) increased with BI 456906 dose.
1 context sentence(design, population, supporting numbers)
Summary · context
To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.
Report a problemFND-3652738606

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

Registered trials2

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

2 trials · 2 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT03591718

A Study to Test Different Doses of BI 456906 in Patients With Obesity

Boehringer Ingelheimn = 13126 Jul 2018 to 30 Apr 2020

Obesity

Trial page ClinicalTrials.govUpdated 22 Mar 2021

CompletedPhase 1NCT03175211

Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 456906 in Healthy Male Volunteers

Boehringer Ingelheimn = 2030 Jun 2017 to 19 Feb 2018

Healthy

Trial page ClinicalTrials.govUpdated 16 Jul 2018

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.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

PepBank is a research reference. Talk to a doctor before you use any peptide.

Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906.

Summary

Results from this study12

Registered trials2

A Study to Test Different Doses of BI 456906 in Patients With Obesity

Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 456906 in Healthy Male Volunteers

Version history

Subjects

Publication types

MeSH terms

Keywords