Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Markers of Vascular Damage

Abstract

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular morbidity and delay the progression of kidney disease in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms underpinning these benefits are not entirely clear. More specifically, it is uncertain whether these agents exert cardiorenal protective effects through a direct action on the vascular wall. The aim of the present study was to evaluate the effects of SGLT2 inhibitors on markers of subclinical vascular damage. Methods: In total, 40 adult patients with T2DM and glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 and age- and gender-matched patients with T2DM and GFR > 60 mL/min/1.73 m2 were consecutively enrolled. Indices of arterial stiffness (pulse wave velocity, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (Alx@75) and central systolic, diastolic, pulse and mean pressure), carotid atherosclerosis (stenosis, intima-media thickness (cIMT) and maximal plaque thickness) and peripheral arterial disease (ankle brachial index (ABI)) were determined. The chi-squared and Mann–Whitney U-test were used to detect differences in categorical and continuous variables between groups, respectively. Results: In total, 15 patients were treated with SGLT2 inhibitors and 25 patients were not receiving these agents. Serum low-density lipoprotein cholesterol levels were lower in the former whereas other cardiovascular risk factors, the prevalence of established cardiovascular disease, anthropometric and demographic characteristics, and vital signs did not differ between the 2 groups. The AIx was lower in patients treated with SGLT2 inhibitors (21.9 ± 11.3 vs. 29.7 ± 12% in patients not treated with SGLT2 inhibitors; p < 0.05). The AIx@75 was also lower in the former (21.3 ± 10.9 and 32.6 ± 11.3%, respectively, p < 0.005). Other markers of arterial stiffness were similar in the 2 groups. In addition, markers of carotid atherosclerosis and the ABI did not differ between patients treated and not treated with SGLT2 inhibitors. Conclusions: Treatment with SGLT2 inhibitors appears to reduce arterial stiffness. Accordingly, these agents might improve cardiovascular outcomes not only in patients with T2DM and established cardiorenal disease but also in lower-risk patients.

Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis

“…Three different GLP-1 RA drugs were investigated in the included studies: liraglutide [ 11 , 12 , 16 , 18 , 23 – 29 ], semaglutide [ 21 ], and exenatide [ 19 , 22 , 30 , 31 ]. Also, five different SGLT2i drugs were studied, including empagliflozin [ 32 , 36 , 38 , 42 ], ipragliflozin [ 33 , 39 , 41 ], tofogliflozin [ 34 , 40 ], dapagliflozin [ 35 – 37 , 42 ], and luseogliflozin [ 40 ]. The range of intervention periods for GLP-1 RA trials ranged from 4 months [ 12 , 13 , 21 , 26 ] to 3 years [ 29 ] and for SGLT2i trials was from 2 weeks [ 38 ] to 3.6 years [ 36 ].…”

“…The literature search yielded 708 related articles after duplicates were removed. Eighteen studies examined the effects of GLP-1 RA [11][12][13][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], and eleven examined the effects of SGLT2i on IMT [32][33][34][35][36][37][38][39][40][41][42]. Studies that did not provide IMT results [43][44][45][46][47][48][49], duplicate data [50][51][52][53][54][55][56], combination therapies without apparent GLP-1 RA effects [57], or assessed IMT of arteries other than the carotid artery were excluded [58][59][60].…”

“…Also, five different SGLT2i drugs were studied, including empagliflozin [32,36,38,42], ipragliflozin [33,39,41], tofogliflozin [34,40], dapagliflozin [35][36][37]42], and luseogliflozin [40]. The range of intervention periods for GLP-1 RA trials ranged from 4 months [12,13,21,26] to 3 years [29] and for SGLT2i trials was from 2 weeks [38] to 3.6 years [36]. All SGLT2i studies [32][33][34][35][36][37][38][39][40][41][42] and fifteen GLP-1 RA studies included T2DM patients [11,12,17,[19][20][21][22][23][24][25][26][27][29][30][31].…”

“…The range of intervention periods for GLP-1 RA trials ranged from 4 months [12,13,21,26] to 3 years [29] and for SGLT2i trials was from 2 weeks [38] to 3.6 years [36]. All SGLT2i studies [32][33][34][35][36][37][38][39][40][41][42] and fifteen GLP-1 RA studies included T2DM patients [11,12,17,[19][20][21][22][23][24][25][26][27][29][30][31]. Italy (n = 7) was the country with the largest number of published articles for GLP-1 RA and Japan for SGLT2i (n = 5).…”