Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes: A Post Hoc Secondary Analysis of the SOUL Randomized Clinical Trial.

Mulvagh SL, Inzucchi SE, Marx N, Poulter NR, Deanfield JE, Pop-Busui R, Emerson SS, Mann JFE, Engelmann MDM, Hovingh GK, Mandavya K, Davicevic-Elez Z and 10 more

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Jeppesen OK, Lorenzatti A, Oguz A, Mankovsky B, Deerochanawong C, Gorgojo-Martinez JJ, Ji L, Bain SC, McGuire DK, Buse JB

JAMA cardiology1 May 2026Cited by 3 (Europe PMC)

PMID41879791PMCIDPMC13019341DOI10.1001/jamacardio.2026.0245PepBankPUB-41879791

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Summary

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

Results from this study11

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered HbA1c versus placebo at 13 weeks (-0.87 percentage points) and at week 156 (estimated difference -0.47 percentage points).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered HbA1c more than placebo, early and after three years.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
HbA1c change at 13 weeks
−0.87 percentage points
oral semaglutide vs placebo
HbA1c ETD at week 156
−0.47 percentage points
oral semaglutide vs placebo
Source sentences
Summary
HbA1c (-0.87 percentage points)
2 context sentences(design, population, supporting numbers)
Summary · context
HbA1c (-0.47 percentage points; 95% CI, -0.52 to -0.42)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979101
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide reduced body weight versus placebo at 13 weeks (-2.54%) and at week 156 (estimated difference -3.26 percentage points).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide reduced body weight more than placebo, early and after three years.
Peptide
Semaglutide
Outcome
DecreaseBody weight change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
Body weight change at 13 weeks
−2.54%
oral semaglutide vs placebo
Body weight ETD at week 156
−3.26 percentage points
oral semaglutide vs placebo
Source sentences
Summary
body weight (-2.54%)
2 context sentences(design, population, supporting numbers)
Summary · context
body weight (-3.26 percentage points; 95% CI, -3.55 to -2.98)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979102
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered systolic blood pressure versus placebo at 13 weeks (-3.84 mm Hg) and at week 156 (estimated difference -1.83 mm Hg).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered systolic blood pressure more than placebo, early and late.
Peptide
Semaglutide
Outcome
DecreaseSystolic blood pressure change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
SBP change at 13 weeks
−3.84 mm Hg
oral semaglutide vs placebo
SBP ETD at week 156
−1.83 mm Hg
oral semaglutide vs placebo
Source sentences
Summary
systolic BP (SBP, -3.84 mm Hg)
2 context sentences(design, population, supporting numbers)
Summary · context
SBP (-1.83 mm Hg; 95% CI, -2.47 to -1.18)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979103
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered pulse pressure versus placebo at 13 weeks (-3.81 mm Hg) and at week 156 (estimated difference -2.17 mm Hg).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered pulse pressure more than placebo, early and after three years.
Peptide
Semaglutide
Outcome
DecreasePulse pressure change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
Pulse pressure change at 13 weeks
−3.81 mm Hg
oral semaglutide vs placebo
Pulse pressure ETD at week 156
−2.17 mm Hg
oral semaglutide vs placebo
Source sentences
Summary
pulse pressure (-3.81 mm Hg)
2 context sentences(design, population, supporting numbers)
Summary · context
pulse pressure (-2.17 mm Hg; 95% CI, -2.72 to -1.61)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979104
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered hsCRP versus placebo at 13 weeks (-18.08%) and at week 156 (estimated treatment ratio 0.77).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered an inflammation marker more than placebo, early and late.
Peptide
Semaglutide
Outcome
DecreasehsCRP change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
hsCRP change at 13 weeks
−18.08%
oral semaglutide vs placebo
hsCRP ETR at week 156
0.77 ratio
oral semaglutide vs placebo
Source sentences
Summary
hsCRP (-18.08%)
2 context sentences(design, population, supporting numbers)
Summary · context
hsCRP (0.77; 95% CI, 0.74-0.81)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979105
06HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered total cholesterol versus placebo at 13 weeks (-7.00%) and at week 156 (estimated treatment ratio 0.99).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered total cholesterol more than placebo, early and after three years.
Peptide
Semaglutide
Outcome
DecreaseTotal cholesterol change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
Total cholesterol change at 13 weeks
−7%
oral semaglutide vs placebo
Total cholesterol ETR at week 156
0.99 ratio
oral semaglutide vs placebo
Source sentences
Summary
total cholesterol (TC, -7.00%)
2 context sentences(design, population, supporting numbers)
Summary · context
TC (0.99; 95% CI, 0.98-1.00)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979106
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered non-HDL cholesterol versus placebo at 13 weeks (-8.02%) and at week 156 (estimated treatment ratio 0.98).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered non-HDL cholesterol more than placebo, early and late.
Peptide
Semaglutide
Outcome
DecreaseNon-HDL cholesterol change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
Non-HDL-C change at 13 weeks
−8.02%
oral semaglutide vs placebo
Non-HDL-C ETR at week 156
0.98 ratio
oral semaglutide vs placebo
Source sentences
Summary
non-high-density lipoprotein cholesterol (non-HDL-C, -8.02%)
2 context sentences(design, population, supporting numbers)
Summary · context
non-HDL-C (0.98; 95% CI, 0.97-0.99)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979107
08HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, HDL cholesterol was lower with oral semaglutide than with placebo at 13 weeks (-4.49%), while the estimated treatment ratio at week 156 was 1.01.
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, HDL cholesterol was lower with oral semaglutide early; the week 156 ratio was 1.01.
Peptide
Semaglutide
Outcome
MixedHDL cholesterol change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
HDL-C change at 13 weeks
−4.49%
oral semaglutide vs placebo
HDL-C ETR at week 156
1.01 ratio
oral semaglutide vs placebo
Source sentences
Summary
HDL-C (-4.49%)
2 context sentences(design, population, supporting numbers)
Summary · context
HDL-C (1.01; 95% CI, 1.01-1.02)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979108
09HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide lowered triglycerides versus placebo at 13 weeks (-8.15%) and at week 156 (estimated treatment ratio 0.94).
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide lowered blood triglycerides more than placebo, early and after three years.
Peptide
Semaglutide
Outcome
DecreaseTriglycerides change
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Measurements
Triglycerides change at 13 weeks
−8.15%
oral semaglutide vs placebo
Triglycerides ETR at week 156
0.94 ratio
oral semaglutide vs placebo
Source sentences
Summary
triglycerides (-8.15%)
2 context sentences(design, population, supporting numbers)
Summary · context
triglycerides (0.94; 95% CI, 0.93-0.96)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979109
10HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide did not significantly change LDL cholesterol versus placebo.
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide did not change LDL cholesterol significantly compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeLDL cholesterol
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Lipids · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Source sentences
Summary
No significant treatment differences were observed for low-density lipoprotein cholesterol
1 context sentence(design, population, supporting numbers)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979110
11HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and ASCVD and/or CKD, oral semaglutide did not significantly change diastolic blood pressure versus placebo.
In plain wordsIn adults with type 2 diabetes and heart or kidney disease, oral semaglutide did not change the lower blood pressure number significantly compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeDiastolic blood pressure
Study
n = 9,650
Comparator
Placebo
Analysis
Primary
Outcome group
Blood pressure · Cardiovascular
Studied dose
maximum 14 mg once daily · oralAs given in this study (human).
Source sentences
Summary
No significant treatment differences were observed for low-density lipoprotein cholesterol or diastolic BP.
1 context sentence(design, population, supporting numbers)
Summary · context
This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.
Report a problemFND-4187979111

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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 postedNCT03914326

A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes

Novo Nordisk A/Sn = 9,65117 Jun 2019 to 23 Aug 2024

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 11 Dec 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
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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