American journal of physiology. Heart and circulatory physiologyJan 24, 2026

Effects of Diabetes Drugs Alone and Combined on Artery Health, Oxidative Stress, and Amyloid Beta Levels

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 25, 2026

Abstract

All treatment regimens were associated with reductions in carotid intima-media thickness (cIMT) and amyloid-β1-40 (Aβ1-40) at 12 months (P<0.05).

Patients treated with liraglutide, empagliflozin, and their combination showed greater reductions in cIMT compared to insulin (-8.2%, -5.6%, and -10.7% vs -1.7%, P<0.05).
Aβ1-40 levels decreased more significantly in patients receiving liraglutide, empagliflozin, and combination therapy compared to insulin (-52.1%, -40.3%, and -50.7% vs -30.7%, P<0.05).
The combination therapy led to the highest proportion of patients achieving cIMT <1.5mm at 12 months (75%), followed by liraglutide (67%) and empagliflozin (54%), compared to insulin (40%; P<0.05).
Patients who experienced a reduction in cIMT to below 1.5mm showed a greater reduction in Aβ1-40 levels than those with cIMT remaining above 1.5mm (-56.2% vs -25.1%, P=0.028).
cIMT regression was associated with reductions in both Aβ1-40 and oxidative stress marker malondialdehyde (MDA) (P<0.05).

Simplified

Carotid intima-media thickness (cIMT), amyloid-β1-40 (Aβ1-40) and oxidative stress are markers of vascular ageing 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 above markers in type-2 diabetes (T2DM). We prospectively studied 183 metformin-treated T2DM patients, propensity-score-matched to 12-month treatment with insulin, liraglutide, empagliflozin or liraglutide plus empagliflozin. Six-segment cIMT and plaque-equivalent lesions (cIMT≥1.5mm) were assessed at baseline, 6 and 12 months; plasma Aβ1-40 and malondialdehyde (MDA) were measured. All regimens were associated with reductions in cIMT and Aβ1-40 at 12 months (P<0.05). MDA decreased overall with the largest reduction in GLP-1RA-based regimens. Compared with insulin, liraglutide, empagliflozin and combination achieved greater reductions in cIMT (-8.2%, -5.6% and -10.7% vs -1.7%, P<0.05) and in Aβ1-40 (-52.1%, -40.3% and -50.7% vs -30.7%, P<0.05). Patients achieving cIMT <1.5mm at 12 months was highest with combination therapy (75%), followed by liraglutide (67%) and empagliflozin (54%) versus insulin (40%; P<0.05). Patients who regressed <1.5mm showed greater reduction in Aβ1-40 than those with ≥1.5mm (-56.2% vs -25.1%, P=0.028). Liraglutide, empagliflozin and 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 to 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.

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Effects of Diabetes Drugs Alone and Combined on Artery Health, Oxidative Stress, and Amyloid Beta Levels

Abstract

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