Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis.

Sattar N, Linetzky B, Ruotolo G, Verma S, Sourij H, Wang H, Vanderman K, Wilson JM, Griffin RM, Stefanski A, Ridker PM

Journal of the American College of Cardiology3 Jun 2026Cited by 1 (Europe PMC)

PMID42233927DOI10.1016/j.jacc.2026.04.044PepBankPUB-42233927

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-ND. Results still quote short attributed sentences.

Results from this study16

16 results from studies that gave the peptide. 16 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced high-sensitivity C-reactive protein by 36.9%, 46.9% and 54.6% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered a blood marker of inflammation (CRP) more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseHigh-sensitivity C-reactive protein at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
hs-CRP geometric mean change vs placebo
−36.9%
5 mg
hs-CRP geometric mean change vs placebo
−46.9%
10 mg
hs-CRP geometric mean change vs placebo
−54.6%
15 mg
Source sentences
Summary
high-sensitivity C-reactive protein (-36.9%, -46.9%, -54.6%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392701
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced interleukin-6 by 25.4%, 27.8% and 30.2% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered the inflammation marker interleukin-6 more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseInterleukin-6 at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
IL-6 geometric mean change vs placebo
−25.4%
5 mg
IL-6 geometric mean change vs placebo
−27.8%
10 mg
IL-6 geometric mean change vs placebo
−30.2%
15 mg
Source sentences
Summary
interleukin-6 (-25.4%, -27.8%, -30.2%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392702
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 10 and 15 mg reduced leukocytes by 8.6% and 10.0% versus placebo at week 72; the 5 mg dose showed no significant change.
In plain wordsIn adults with obesity, tirzepatide 10 and 15 mg lowered white blood cell counts more than placebo at 72 weeks; 5 mg did not.
Peptide
Tirzepatide
Outcome
DecreaseLeukocyte count at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
Leukocyte geometric mean change vs placebo
−8.6%
10 mg
Leukocyte geometric mean change vs placebo
−10%
15 mg
Source sentences
Summary
leukocytes (not significant [NS], -8.6%, -10.0%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392703
04HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced the homeostatic model assessment of insulin resistance by 26.4%, 35.5% and 39.1% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered an insulin resistance score more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseHOMA-IR at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
HOMA-IR geometric mean change vs placebo
−26.4%
5 mg
HOMA-IR geometric mean change vs placebo
−35.5%
10 mg
HOMA-IR geometric mean change vs placebo
−39.1%
15 mg
Source sentences
Summary
homeostatic model assessment of insulin resistance (-26.4%, -35.5%, -39.1%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392704
05HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced leptin by 44.4%, 59.3% and 61.4% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered the fat hormone leptin more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseLeptin at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Adipokines · Metabolic and weight
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
Leptin geometric mean change vs placebo
−44.4%
5 mg
Leptin geometric mean change vs placebo
−59.3%
10 mg
Leptin geometric mean change vs placebo
−61.4%
15 mg
Source sentences
Summary
leptin (-44.4%, -59.3%, -61.4%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392705
06HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced gamma-glutamyl transferase by 18.6%, 21.6% and 32.7% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered the liver enzyme gamma-glutamyl transferase more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseGamma-glutamyl transferase at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
GGT geometric mean change vs placebo
−18.6%
5 mg
GGT geometric mean change vs placebo
−21.6%
10 mg
GGT geometric mean change vs placebo
−32.7%
15 mg
Source sentences
Summary
gamma-glutamyl transferase (-18.6%, -21.6%, -32.7%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392706
07HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced fibroblast growth factor-21 by 27.4%, 27.6% and 39.9% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered the metabolic stress hormone FGF-21 more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseFibroblast growth factor-21 at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Adipokines · Metabolic and weight
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
FGF-21 geometric mean change vs placebo
−27.4%
5 mg
FGF-21 geometric mean change vs placebo
−27.6%
10 mg
FGF-21 geometric mean change vs placebo
−39.9%
15 mg
Source sentences
Summary
fibroblast growth factor-21 (-27.4%, -27.6%, -39.9%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392707
08HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg increased adiponectin by 21.1%, 35.1% and 47.7% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide raised adiponectin, a hormone linked to metabolic health, more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
IncreaseAdiponectin at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Adipokines · Metabolic and weight
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
Adiponectin geometric mean change vs placebo
21.1%
5 mg
Adiponectin geometric mean change vs placebo
35.1%
10 mg
Adiponectin geometric mean change vs placebo
47.7%
15 mg
Source sentences
Summary
adiponectin (21.1%, 35.1%, 47.7%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392708
09HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 15 mg reduced free fatty acids by 17.1% versus placebo at week 72; the 5 and 10 mg doses showed no significant change.
In plain wordsIn adults with obesity, tirzepatide 15 mg lowered free fatty acids more than placebo at 72 weeks; lower doses did not.
Peptide
Tirzepatide
Outcome
DecreaseFree fatty acids at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Metabolic and weight
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
Free fatty acids geometric mean change vs placebo
−17.1%
15 mg
Source sentences
Summary
free fatty acids (NS, NS, -17.1%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392709
10HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 10 and 15 mg reduced soluble intercellular adhesion molecule-1 by 9.7% and 11.1% versus placebo at week 72; the 5 mg dose showed no significant change.
In plain wordsIn adults with obesity, tirzepatide 10 and 15 mg lowered a blood vessel stress marker (sICAM-1) more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseSoluble intercellular adhesion molecule-1 at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Vascular function · Cardiovascular
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
sICAM-1 geometric mean change vs placebo
−9.7%
10 mg
sICAM-1 geometric mean change vs placebo
−11.1%
15 mg
Source sentences
Summary
soluble intercellular adhesion molecule-1 (NS, -9.7%, -11.1%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392710
11HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced E-selectin by 12.6%, 20.0% and 26.4% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered a blood vessel stress marker (E-selectin) more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreaseE-selectin at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Vascular function · Cardiovascular
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
E-selectin geometric mean change vs placebo
−12.6%
5 mg
E-selectin geometric mean change vs placebo
−20%
10 mg
E-selectin geometric mean change vs placebo
−26.4%
15 mg
Source sentences
Summary
E-selectin (-12.6%, -20.0%, -26.4%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392711
12HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 5, 10 and 15 mg reduced plasminogen activator inhibitor-1 antigen by 41.4%, 35.6% and 44.3% versus placebo at week 72.
In plain wordsIn adults with obesity, tirzepatide lowered a blood clotting marker (PAI-1) more than placebo at 72 weeks.
Peptide
Tirzepatide
Outcome
DecreasePlasminogen activator inhibitor-1 antigen at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Bleeding and clotting · Cardiovascular
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
PAI-1:Ag geometric mean change vs placebo
−41.4%
5 mg
PAI-1:Ag geometric mean change vs placebo
−35.6%
10 mg
PAI-1:Ag geometric mean change vs placebo
−44.3%
15 mg
Source sentences
Summary
plasminogen activator inhibitor-1:Ag (-41.4%, -35.6%, -44.3%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392712
13HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide 15 mg reduced platelets by 6.0% versus placebo at week 72; the 5 and 10 mg doses showed no significant change.
In plain wordsIn adults with obesity, tirzepatide 15 mg lowered platelet counts more than placebo at 72 weeks; lower doses did not.
Peptide
Tirzepatide
Outcome
DecreasePlatelet count at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Bleeding and clotting · Cardiovascular
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Measurements
Platelet geometric mean change vs placebo
−6%
15 mg
Source sentences
Summary
platelets (NS, NS, -6.0%)
2 context sentences(design, population, supporting numbers)
Summary · context
At week 72, tirzepatide was associated with significantly greater reductions (negative values) or increases (positive values) in biomarker geometric means compared with placebo.
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392713
14HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide showed no consistent association with changes in fibrinogen versus placebo.
In plain wordsIn adults with obesity, tirzepatide showed no consistent change in fibrinogen compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeFibrinogen at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Source sentences
Summary
No consistent associations were observed between tirzepatide and changes in fibrinogen, tissue plasminogen activator:Ag, or thrombomodulin.
1 context sentence(design, population, supporting numbers)
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392714
15HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide showed no consistent association with changes in tissue plasminogen activator antigen versus placebo.
In plain wordsIn adults with obesity, tirzepatide showed no consistent change in a blood clotting marker (tPA) compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeTissue plasminogen activator antigen at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Bleeding and clotting · Cardiovascular
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Source sentences
Summary
No consistent associations were observed between tirzepatide and changes in fibrinogen, tissue plasminogen activator:Ag, or thrombomodulin.
1 context sentence(design, population, supporting numbers)
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392715
16HumanRandomized controlled trialEfficacy outcome
In adults with obesity, tirzepatide showed no consistent association with changes in thrombomodulin versus placebo.
In plain wordsIn adults with obesity, tirzepatide showed no consistent change in thrombomodulin compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeThrombomodulin at week 72
Study
n = 392
Comparator
Placebo
Analysis
Primary
Outcome group
Bleeding and clotting · Cardiovascular
Studied dose
5, 10, or 15 mg · 72 weeksAs given in this study (human).
Source sentences
Summary
No consistent associations were observed between tirzepatide and changes in fibrinogen, tissue plasminogen activator:Ag, or thrombomodulin.
1 context sentence(design, population, supporting numbers)
Summary · context
The aforementioned biomarkers were assayed from plasma samples, collected at baseline, 24 weeks, and 72 weeks, from 100 randomly selected participants from each group of the SURMOUNT-1 trial who completed treatment with once-weekly placebo or tirzepatide 5, 10, or 15 mg (n = 392 after low sample volumes excluded).
Report a problemFND-4223392716

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 · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04184622

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight

Eli Lilly and Companyn = 2,5394 Dec 2019 to 6 Jul 2024

Overweight · Obesity

Trial page ClinicalTrials.govUpdated 24 Jul 2025

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
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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