GLP-1 receptor agonists, SGLT-2 inhibitors, and their combination: effects on carotid atherosclerosis regression, oxidative stress, and amyloid-β1-40 in diabetes.

Ikonomidis I, Papageorgiou A, Pavlidis G, Georgiopoulos G, Katogiannis K, Maratou E, Thymis J, Pliouta L, Kountouri A, Korakas E, Kostelli G, Parissis J, Nikolaou PE, Andreadou I, Lambadiari V

American journal of physiology. Heart and circulatory physiology24 Jan 2026Cited by 1 (Europe PMC)

PMID41579346DOI10.1152/ajpheart.00996.2025PepBankPUB-41579346

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Summary

Carotid intima-media thickness (cIMT), amyloid-β1-40 (Aβ1-40), and oxidative stress are markers of vascular aging and cardiovascular risk. We compared the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on the aforementioned markers in type 2 diabetes (T2DM). We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin. Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured. All regimens were associated with reductions in cIMT and Aβ1-40 at 12 mo (P < 0.05). MDA decreased overall with the largest reduction in GLP-1RA-based regimens. Compared with insulin, liraglutide, empagliflozin, and their combination achieved greater reductions in cIMT (-8.2, -5.6, and -10.7% vs. -1.7%, P P < 0.05). Patients achieving cIMT P < 0.05). Patients who regressed P = 0.028). Liraglutide, empagliflozin, and their combination induced greater reduction of cIMT (-8.2, -5.6, and -10.7% vs. -1.7%) and Aβ1-40 (-52.1, -40.3, and -50.7% vs. -30.7%; P < 0.05) compared with insulin. cIMT regression was associated with Aβ1-40 and MDA reductions (P < 0.05). In T2DM patients, GLP-1RA and SGLT-2i-particularly in combination-were associated with improvements in carotid atherosclerotic burden, amyloid-related vascular injury, and oxidative stress.NEW & NOTEWORTHY We investigated the effect of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on carotid intima-media thickness (cIMT) and amyloid-β1-40 (Aβ1-40) in diabetes. Twelve-month treatment with GLP-1RA, SGLT-2i, and their combination confers significant reductions in cIMT and Aβ1-40 compared with insulin. cIMT regression was associated with Aβ1-40 and malondialdehyde reductions. Our findings support that newer antidiabetic agents can favorably modify structural and biochemical markers of atherosclerosis.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

3 results from studies that gave the peptide. 3 results from people.

01HumanObservational studyEfficacy outcome
In metformin-treated adults with type 2 diabetes, liraglutide was associated with a greater cIMT reduction than insulin.
In plain wordsIn metformin-treated adults with type 2 diabetes, liraglutide was linked to a greater reduction in carotid artery thickness than insulin.
Peptide
Liraglutide
Outcome
DecreaseCarotid intima-media thickness
Study
n: not reported in source
Comparator
Insulin
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · 12 moAs given in this study (human).
Measurements
cIMT reduction
−8.2%
liraglutide
cIMT reduction
−1.7%
insulin
Source sentences
Summary
Compared with insulin, liraglutide, empagliflozin, and their combination achieved greater reductions in cIMT (-8.2, -5.6, and -10.7% vs. -1.7%, P P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
Show in the study text Report a problemFND-4157934601
02HumanObservational studyEfficacy outcome
In metformin-treated adults with type 2 diabetes, liraglutide was associated with a greater plasma amyloid-beta1-40 reduction than insulin.
In plain wordsIn metformin-treated adults with type 2 diabetes, liraglutide was linked to a greater plasma amyloid-beta1-40 reduction than insulin.
Peptide
Liraglutide
Outcome
DecreasePlasma amyloid-β1-40
Study
n: not reported in source
Comparator
Insulin
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated · 12 moAs given in this study (human).
Measurements
Aβ1-40 reduction
−52.1%
liraglutide
Aβ1-40 reduction
−30.7%
insulin
Source sentences
Summary
Compared with insulin, liraglutide, empagliflozin, and their combination achieved greater reductions in cIMT (-8.2, -5.6, and -10.7% vs. -1.7%, P P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
Show in the study text Report a problemFND-4157934602
03HumanObservational studyEfficacy outcome
In metformin-treated adults with type 2 diabetes, a greater proportion receiving liraglutide had cIMT below 1.5 mm at 12 months than those receiving insulin.
In plain wordsIn metformin-treated adults with type 2 diabetes, more liraglutide-treated participants reached cIMT below 1.5 mm than insulin-treated participants.
Peptide
Liraglutide
Outcome
IncreasecIMT below 1.5 mm at 12 months
Study
n: not reported in source
Comparator
Insulin
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · 12 moAs given in this study (human).
Measurements
Patients with cIMT < 1.5 mm
67%
liraglutide
Patients with cIMT < 1.5 mm
40%
insulin
Source sentences
Summary
Patients achieving cIMT P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
Show in the study text Report a problemFND-4157934605

Studies that did not test the peptide alone9

In this study, Liraglutide 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 Liraglutide.

04HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
Across metformin-treated adults with type 2 diabetes receiving the study regimens, malondialdehyde decreased overall, with the largest reduction in GLP-1 receptor agonist-based regimens.
In plain wordsAcross the study regimens in metformin-treated adults with type 2 diabetes, malondialdehyde decreased overall, most in GLP-1 receptor agonist-based regimens.
Peptide
Liraglutide
Outcome
DecreaseMalondialdehyde
Study
n = 183
Outcome group
Inflammation markers · Cardiovascular
Source sentences
Summary
MDA decreased overall with the largest reduction in GLP-1RA-based regimens.
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934606
05HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
Across insulin, liraglutide, empagliflozin, and liraglutide plus empagliflozin regimens in metformin-treated adults with type 2 diabetes, cIMT decreased at 12 months.
In plain wordsAcross the study regimens in adults with type 2 diabetes, carotid artery thickness decreased at 12 months.
Peptide
Liraglutide
Outcome
DecreasecIMT reduction
Study
n = 183
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
All regimens were associated with reductions in cIMT and Aβ1-40 at 12 mo (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934607
06HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
Across insulin, liraglutide, empagliflozin, and liraglutide plus empagliflozin regimens in metformin-treated adults with type 2 diabetes, plasma amyloid-beta1-40 decreased at 12 months.
In plain wordsAcross the study regimens in adults with type 2 diabetes, plasma amyloid-beta1-40 decreased at 12 months.
Peptide
Liraglutide
Outcome
DecreasePlasma amyloid-beta1-40 reduction
Study
n = 183
Outcome group
Aging markers · Cardiovascular
Source sentences
Summary
All regimens were associated with reductions in cIMT and Aβ1-40 at 12 mo (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934608
07HumanNot a test of Liraglutide aloneObservational studyOther
Across study regimens including liraglutide, cIMT regression was associated with amyloid-beta1-40 reduction.
In plain wordsAcross the study regimens, cIMT regression was linked to lower amyloid-beta1-40.
Peptide
Liraglutide
Outcome
Not applicableAssociation of cIMT regression with amyloid-beta1-40 reduction
Study
n = 183
Outcome group
Aging markers · Cardiovascular
Source sentences
Summary
cIMT regression was associated with Aβ1-40 and MDA reductions (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934611
08HumanNot a test of Liraglutide aloneObservational studyOther
Across study regimens including liraglutide, cIMT regression was associated with malondialdehyde reduction.
In plain wordsAcross the study regimens, cIMT regression was linked to lower malondialdehyde.
Peptide
Liraglutide
Outcome
Not applicableAssociation of cIMT regression with malondialdehyde reduction
Study
n = 183
Outcome group
Inflammation markers · Cardiovascular
Source sentences
Summary
cIMT regression was associated with Aβ1-40 and MDA reductions (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934612
09HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In metformin-treated adults with type 2 diabetes, liraglutide plus empagliflozin was associated with a greater cIMT reduction than insulin.
In plain wordsIn metformin-treated adults with type 2 diabetes, liraglutide plus empagliflozin was linked to a greater reduction in carotid artery thickness than insulin.
Peptide
Liraglutide
Outcome
DecreaseCarotid intima-media thickness
Study
n: not reported in source
Comparator
Insulin
Outcome group
Cardiovascular events · Cardiovascular
Measurements
cIMT reduction
−10.7%
liraglutide plus empagliflozin
cIMT reduction
−1.7%
insulin
Source sentences
Summary
Compared with insulin, liraglutide, empagliflozin, and their combination achieved greater reductions in cIMT (-8.2, -5.6, and -10.7% vs. -1.7%, P P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934603
10HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In metformin-treated adults with type 2 diabetes, liraglutide plus empagliflozin was associated with a greater plasma amyloid-beta1-40 reduction than insulin.
In plain wordsIn metformin-treated adults with type 2 diabetes, liraglutide plus empagliflozin was linked to a greater plasma amyloid-beta1-40 reduction than insulin.
Peptide
Liraglutide
Outcome
DecreasePlasma amyloid-β1-40
Study
n: not reported in source
Comparator
Insulin
Outcome group
Aging markers · Cardiovascular
Measurements
Aβ1-40 reduction
−50.7%
liraglutide plus empagliflozin
Aβ1-40 reduction
−30.7%
insulin
Source sentences
Summary
Compared with insulin, liraglutide, empagliflozin, and their combination achieved greater reductions in cIMT (-8.2, -5.6, and -10.7% vs. -1.7%, P P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934604
11HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In metformin-treated adults with type 2 diabetes, 75% receiving liraglutide plus empagliflozin achieved cIMT below 1.5 mm at 12 months versus 40% receiving insulin.
In plain wordsIn adults with type 2 diabetes, more people receiving liraglutide plus empagliflozin reached cIMT below 1.5 mm than those receiving insulin.
Peptide
Liraglutide
Outcome
IncreasecIMT below 1.5 mm at 12 months
Study
n: not reported in source
Comparator
Insulin
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Patients with cIMT < 1.5 mm
75%
liraglutide plus empagliflozin
Patients with cIMT < 1.5 mm
40%
insulin
Source sentences
Summary
Patients achieving cIMT P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934609
12HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
Across study regimens including liraglutide, patients whose cIMT regressed below 1.5 mm had a greater amyloid-beta1-40 reduction than those with cIMT at least 1.5 mm.
In plain wordsAcross study regimens including liraglutide, amyloid-beta1-40 fell more with cIMT below 1.5 mm than with cIMT at least 1.5 mm.
Peptide
Liraglutide
Outcome
DecreaseAmyloid-beta1-40 reduction by cIMT regression
Study
n: not reported in source
Comparator
cIMT at least 1.5 mm at 12 months
Outcome group
Aging markers · Cardiovascular
Measurements
Amyloid-beta1-40 reduction
−56.2%
cIMT < 1.5 mm
Amyloid-beta1-40 reduction
−25.1%
cIMT at least 1.5 mm
Source sentences
Summary
Patients who regressed P = 0.028).
2 context sentences(design, population, supporting numbers)
Summary · context
We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-mo treatment with insulin, liraglutide, empagliflozin, or liraglutide plus empagliflozin.
Summary · context
Six-segment cIMT and plaque-equivalent lesions (cIMT ≥ 1.5 mm) were assessed at baseline, 6, and 12 mo; plasma Aβ1-40 and malondialdehyde (MDA) were measured.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4157934610

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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, 11:11 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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GLP-1 receptor agonists, SGLT-2 inhibitors, and their combination: effects on carotid atherosclerosis regression, oxidative stress, and amyloid-β1-40 in diabetes.

Summary

Results from this study12

Studies that did not test the peptide alone9

Version history

Subjects

Publication types

MeSH terms

Keywords