Proteomic effects of short-term liraglutide vs. placebo in a blinded crossover RCT: Implications for efficacy, safety, and comparison with semaglutide.

Stefanakis K, Gutierrez de Piñeres V, Veeragandham P, Mantzoros CS

Metabolism: clinical and experimental7 Jan 2026Cited by 3 (Europe PMC)

PMID41513169DOI10.1016/j.metabol.2026.156493PepBankPUB-41513169

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: Publisher copyright. Results still quote short attributed sentences.

Results from this study19

17 results from studies that gave the peptide. 17 results from people.

01HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide significantly modulated 124 plasma and serum proteins versus placebo.
In plain wordsIn adults with obesity, liraglutide changed 124 measured blood proteins more than placebo.
Peptide
Liraglutide
Outcome
MixedPlasma and serum protein modulation
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Measurements
Proteins modulated
124 proteins
liraglutide versus placebo
Proteins with FDR < 0.05
57 proteins
liraglutide versus placebo
Source sentences
Summary
Liraglutide significantly modulated 124 proteins (57 FDR < 0.05); 85 % of effects persisted after weight adjustment, indicating largely weight-independent actions.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316901
02HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide upregulated pancreatic lipase versus placebo.
In plain wordsIn adults with obesity, liraglutide increased pancreatic lipase more than placebo.
Peptide
Liraglutide
Outcome
IncreasePancreatic lipase
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316902
03HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide upregulated CTRB1 versus placebo.
In plain wordsIn adults with obesity, liraglutide increased CTRB1 more than placebo.
Peptide
Liraglutide
Outcome
IncreaseCTRB1
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316903
04HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide upregulated CTRB2 versus placebo.
In plain wordsIn adults with obesity, liraglutide increased CTRB2 more than placebo.
Peptide
Liraglutide
Outcome
IncreaseCTRB2
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316904
05HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide upregulated PRSS2 versus placebo.
In plain wordsIn adults with obesity, liraglutide increased PRSS2 more than placebo.
Peptide
Liraglutide
Outcome
IncreasePRSS2
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316905
06HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide downregulated ACE versus placebo.
In plain wordsIn adults with obesity, liraglutide lowered ACE more than placebo.
Peptide
Liraglutide
Outcome
DecreaseAngiotensin-converting enzyme
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316906
07HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide downregulated NOS3 versus placebo.
In plain wordsIn adults with obesity, liraglutide lowered NOS3 more than placebo.
Peptide
Liraglutide
Outcome
DecreaseEndothelial nitric oxide synthase
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316907
08HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide downregulated FAP versus placebo.
In plain wordsIn adults with obesity, liraglutide lowered FAP more than placebo.
Peptide
Liraglutide
Outcome
DecreaseFibroblast activation protein
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316908
09HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide strongly suppressed myostatin versus placebo.
In plain wordsIn adults with obesity, liraglutide lowered myostatin more than placebo.
Peptide
Liraglutide
Outcome
DecreaseMyostatin
Study
n = 20
Comparator
Placebo
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Measurements
Log2 fold change
−0.41
myostatin
Source sentences
Summary
Myostatin (MSTN) was strongly suppressed (log₂ fold change -0.41; p = 1.7 × 10^-6), with concurrent rises in its inhibitors WFIKKN2 and BMPR1A.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316909
10HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide increased WFIKKN2 versus placebo.
In plain wordsIn adults with obesity, liraglutide increased WFIKKN2 more than placebo.
Peptide
Liraglutide
Outcome
IncreaseWFIKKN2
Study
n = 20
Comparator
Placebo
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Myostatin (MSTN) was strongly suppressed (log₂ fold change -0.41; p = 1.7 × 10^-6), with concurrent rises in its inhibitors WFIKKN2 and BMPR1A.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316910
11HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide increased BMPR1A versus placebo.
In plain wordsIn adults with obesity, liraglutide increased BMPR1A more than placebo.
Peptide
Liraglutide
Outcome
IncreaseBMPR1A
Study
n = 20
Comparator
Placebo
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Myostatin (MSTN) was strongly suppressed (log₂ fold change -0.41; p = 1.7 × 10^-6), with concurrent rises in its inhibitors WFIKKN2 and BMPR1A.
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316911
12HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide effects had 70-75% directional overlap with a published semaglutide signature.
In plain wordsIn adults with obesity, liraglutide protein changes overlapped 70-75% with a published semaglutide signature.
Peptide
Liraglutide
Outcome
Not applicableDirectional overlap with published semaglutide signature
Study
n = 20
Comparator
Published semaglutide signature
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Measurements
Directional overlap
70 to 75%
liraglutide and semaglutide signatures
Source sentences
Summary
Liraglutide shared 70-75 % directional overlap with semaglutide, with 25-30 % unique effects enriched in vascular, neurodevelopmental, and musculoskeletal pathways.
3 context sentences(design, population, supporting numbers)
Summary · context
We profiled short-term liraglutide-induced protein changes and compared them with published semaglutide signatures.
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Summary · context
Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature.
Report a problemFND-4151316912
13HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide-downregulated proteins were genetically linked to coronary artery disease.
In plain wordsIn adults with obesity, proteins lowered by liraglutide were genetically linked to coronary artery disease.
Peptide
Liraglutide
Outcome
Not applicableCoronary artery disease genetic linkage
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Downregulated proteins were genetically linked to coronary artery disease and type 2 diabetes (FDR < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316914
14HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide-downregulated proteins were genetically linked to type 2 diabetes.
In plain wordsIn adults with obesity, proteins lowered by liraglutide were genetically linked to type 2 diabetes.
Peptide
Liraglutide
Outcome
Not applicableType 2 diabetes genetic linkage
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Source sentences
Summary
Downregulated proteins were genetically linked to coronary artery disease and type 2 diabetes (FDR < 0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Report a problemFND-4151316915
15HumanRandomized controlled trialMechanism
In adults with obesity, 85% of liraglutide protein effects persisted after weight adjustment.
In plain wordsIn adults with obesity, 85% of liraglutide protein effects remained after accounting for weight.
Peptide
Liraglutide
Outcome
Not applicableWeight-adjusted protein effects
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Measurements
Protein effects persisting after weight adjustment
85%
liraglutide effects
Source sentences
Summary
Liraglutide significantly modulated 124 proteins (57 FDR < 0.05); 85 % of effects persisted after weight adjustment, indicating largely weight-independent actions.
2 context sentences(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Summary · context
Mixed-effects models tested Time×Treatment interactions with and without weight adjustment.
Report a problemFND-4151316917
16HumanRandomized controlled trialMechanism
In adults with obesity, liraglutide had 25-30% unique protein effects enriched in vascular, neurodevelopmental, and musculoskeletal pathways versus a published semaglutide signature.
In plain wordsIn adults with obesity, 25-30% of liraglutide protein effects were unique versus a published semaglutide signature.
Peptide
Liraglutide
Outcome
Not applicableProteomic effects unique versus semaglutide
Study
n = 20
Comparator
Published semaglutide signature
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Measurements
Unique effects range
25 to 30%
liraglutide versus published semaglutide signature
Source sentences
Summary
Liraglutide shared 70-75 % directional overlap with semaglutide, with 25-30 % unique effects enriched in vascular, neurodevelopmental, and musculoskeletal pathways.
3 context sentences(design, population, supporting numbers)
Summary · context
We profiled short-term liraglutide-induced protein changes and compared them with published semaglutide signatures.
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Summary · context
Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature.
Report a problemFND-4151316918
17HumanRandomized controlled trialOther
In adults with obesity, a semaglutide-based classifier distinguished liraglutide from placebo.
In plain wordsIn adults with obesity, a semaglutide-based classifier distinguished liraglutide from placebo.
Peptide
Liraglutide
Outcome
Not applicableClassifier distinction from placebo
Study
n = 20
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
3 mg daily · 5 weeksAs given in this study (human).
Measurements
AUC
0.82
classifier distinguishing liraglutide from placebo
Sensitivity
0.89
classifier distinguishing liraglutide from placebo
Specificity
0.6
classifier distinguishing liraglutide from placebo
Source sentences
Summary
A semaglutide-based classifier distinguished liraglutide from placebo (AUC = 0.82; sensitivity 0.89; specificity 0.60).
2 context sentences(design, population, supporting numbers)
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Summary · context
Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature.
Report a problemFND-4151316919

Studies that did not test the peptide alone2

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

18HumanNot a test of Semaglutide aloneRandomized controlled trialOther
In adults with obesity, the published semaglutide signature had 70-75% directional overlap with liraglutide effects.
In plain wordsA published semaglutide signature overlapped 70-75% with liraglutide protein changes.
Peptide
Semaglutide
Outcome
Not applicableDirectional overlap with liraglutide effects
Study
n = 20
Comparator
Liraglutide effects
Outcome group
Receptor activity and mechanism · Pharmacology
Measurements
Directional overlap
70 to 75%
liraglutide and semaglutide signatures
Source sentences
Summary
Liraglutide shared 70-75 % directional overlap with semaglutide, with 25-30 % unique effects enriched in vascular, neurodevelopmental, and musculoskeletal pathways.
3 context sentences(design, population, supporting numbers)
Summary · context
We profiled short-term liraglutide-induced protein changes and compared them with published semaglutide signatures.
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Summary · context
Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4151316913
19HumanNot a test of Semaglutide aloneRandomized controlled trialOther
In adults with obesity, a semaglutide-based classifier distinguished liraglutide from placebo.
In plain wordsA semaglutide-based classifier distinguished liraglutide from placebo.
Peptide
Semaglutide
Outcome
Not applicableSemaglutide-based classifier performance
Study
n = 20
Comparator
Liraglutide versus placebo
Outcome group
Receptor activity and mechanism · Pharmacology
Measurements
AUC
0.82
classifier
Sensitivity
0.89
classifier
Specificity
0.6
classifier
Source sentences
Summary
A semaglutide-based classifier distinguished liraglutide from placebo (AUC = 0.82; sensitivity 0.89; specificity 0.60).
3 context sentences(design, population, supporting numbers)
Summary · context
We profiled short-term liraglutide-induced protein changes and compared them with published semaglutide signatures.
Summary · context
In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout.
Summary · context
Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4151316916

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 ongoing · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 4NCT02944500

Saxenda: Underlying Mechanisms and Clinical Outcomes

Beth Israel Deaconess Medical Centern = 28Nov 2016 to est. Jun 2027

Obesity

Trial page ClinicalTrials.govUpdated 1 May 2026

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 3Current
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:06 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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