Abstract
Imbalance between oxidative stress burden and antioxidant capacity is implicated in the course of atherosclerosis among type 2 diabetic patients. We addressed the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on levels of oxidant and antioxidant biomarkers. We recruited a total of 160 type 2 diabetics, who received insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40), or their combination (GLP-1RA+SGLT-2i) (n = 40). We measured at baseline, at 4 and at 12 months of treatment: (a) Thiobarbituric Acid Reactive Substances (TBARS), (b) Malondialdehyde (MDA), (c) Reducing Power (RP), (d) 2,2¢-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS) and (e) Total Antioxidant Capacity TAC). Dual treatment resulted in significant improvement of TBARS, MDA, and ABTS at four months compared with the other groups (p < 0.05 for all comparisons). At twelve months, all participants improved TBARS, MDA, and ABTS (p < 0.05). At 12 months, GLP1-RA and GLP-1RA+SGLT2-i provided a greater reduction of TBARS (−8.76% and −9.83%) compared with insulin or SGLT2i (−0.5% and 3.22%), (p < 0.05). GLP1-RA and GLP-1RA+SGLT-2i showed a greater reduction of MDA (−30.15% and −31.44%) compared with insulin or SGLT2i (4.72% and −3.74%), (p < 0.05). SGLT2i and GLP-1RA+SGLT2-i showed increase of ABTS (12.87% and 14.13%) compared with insulin or GLP1-RA (2.44% and −3.44%), (p < 0.05). Only combined treatment resulted in increase of TAC compared with the other groups after 12 months of treatment (p < 0.05).12-month treatment with GLP1-RA and SGLT2i resulted in reduction of biomarkers responsible for oxidative modifications and increase of antioxidant biomarker, respectively. The combination treatment was superior and additive to each separate agent and also the beneficial effects appeared earlier.
Highlights
The incidence of Type 2 Diabetes Mellitus is increasing rapidly worldwide resulting in increased atherosclerotic cardiovascular complications and excess cardiovascular morbidity and mortality in diabetics compared to the general population [1,2,3,4,5].Oxidative stress confers remarkably to the detrimental cardiovascular effects of DM by enhancing atherosclerotic processes [6,7]
Six distinct metabolic pathways have been found to contribute to reactive oxygen (ROS) production in diabetes because of sustained hyperglycemia namely: (1) enolization and α-ketoaldehyde formation, (2) PKC activation, (3) dicarbonyl formation and glycation, (4) sorbitol metabolism, and (5) hexosamine metabolism increasing the oxidative burden and tissue damage including b-pancreatic cells [8]
Two novel antidiabetic classes of agents, SGLT2i and GLP1-RA have been approved for diabetic patients who pose high cardiovascular risk, and they are advocated even as a first line treatment in patients at risk by the running guidelines [9]
Summary
The incidence of Type 2 Diabetes Mellitus is increasing rapidly worldwide resulting in increased atherosclerotic cardiovascular complications and excess cardiovascular morbidity and mortality in diabetics compared to the general population [1,2,3,4,5].Oxidative stress confers remarkably to the detrimental cardiovascular effects of DM by enhancing atherosclerotic processes [6,7]. Two novel antidiabetic classes of agents, SGLT2i and GLP1-RA have been approved for diabetic patients who pose high cardiovascular risk, and they are advocated even as a first line treatment in patients at risk by the running guidelines [9]. These agents exert their favorable cardiovascular actions in different ways; GLP1-RA are mainly considered to have anti-atherogenic and anti-inflammatory properties, while SGLT-2i act primarily on vascular hemodynamics, but they are both proposed to reduce oxidative stress burden and enhance antioxidant capacity [10,11,12].
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