scholarly journals Effects of glucagon like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on vascular function and myocardial work index in patient with type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Ikonomidis ◽  
G Pavlidis ◽  
J Thymis ◽  
D Birba ◽  
A Kalogeris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Function ◽  
Myocardial Dysfunction ◽  
Post Treatment ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Work Index ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background/Introduction Type-2 diabetes mellitus (T2DM) is associated with endothelial and myocardial dysfunction. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on vascular and cardiac function of T2DM patients. Methods A hundred-sixty T2DM patients were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (marker of glycocalyx thickness), b) pulse wave velocity (PWV), central systolic blood pressure (cSBP), c) global LV longitudinal (GLS), circumferential (GCS) and radial (GRS) strain, d) the ratio PWV/GLS, as an index of ventricular-arterial interaction, e) myocardial work index (GWI) using speckle tracking imaging. Results Twelve months post-treatment, all patients improved PBR, PWV, GLS, GCS and GRS (p<0.05). GLP-1RA, SGLT-2i and their combination showed a greater reduction of PBR, PWV and cSBP than insulin, despite a similar HbA1c reduction (p<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater decrease of PWV/GLS (28.1% and 31% vs. 11.1% and 14.5%) and a greater increase of GWI (12.7% and 17.4% vs. 3.1% and 2%) compared with insulin or SGLT-2i. SGLT-2i or GLP-1RA+SGLT-2i showed a greater decrease of PWV (10.1% and 13%), cSBP than insulin or GLP-1RA (PWV: 3.6% and 8.6%) (p<0.05 for all comparisons) (Table 1). The dual therapy showed the greatest effect on measured markers in patients with LVEF <55% (p<0.05). Conclusions Twelve-month treatment with GLP-1RA, SGLT-2i and their combination showed a greater improvement of vascular markers and effective cardiac work than insulin in T2DM. The combined therapy was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

scholarly journals Glucagon like peptide-1 receptor agonists and their combination with sodium-glucose cotransporter-2 inhibitors improve myocardial deformation and work index in type-2 diabetes after 12-month treatment

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Ikonomidis ◽  
G Pavlidis ◽  
J Thymis ◽  
D Birba ◽  
A Kalogeris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combined Treatment ◽  
Post Treatment ◽  
Myocardial Deformation ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Work Index ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background/Introduction Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on LV myocardial function of T2DM patients. Methods A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) global LV longitudinal strain (GLS), systolic (LongSr) and diastolic (LongSrE) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial global work index (GWI), global constructive (GCW) and global wasted myocardial work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging. Results At 4 and 12 months post-treatment, all patients improved GLS, GCS, GRS and pUtwVel (p<0.05). At 12 months, GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of GLS (11.5% and 13% vs. 6.8% and 2.3%), GCS (11.9% and 14.6% vs. 7.3% and 3.4%), GRS (3.8% and 4.3% vs. 2.2% and 1.6%), GWI (12.7% and 17.4% vs. 3.1% and 2%), GCW (12.3% and 15% vs. 2.2% and 7.8%) and a greater reduction of GWW (38.7% and 41.6% vs. 13.5% and 4.9%) compared with insulin or SGLT-2i, despite a similar HbA1c reduction (p<0.05 for all comparisons) (Table). Patients under combined treatment with GLP-1RA+SGLT-2i achieved a 2-fold reduction of pTw and a 2-fold increase of pUtwVel than those under each one regimen or insulin (p<0.05). The dual therapy showed the greatest effect on measured myocardial markers in patients with LVEF <55% (p<0.05). Conclusions Twelve-month treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i showed a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

scholarly journals Effects of glucagon like peptide-1 receptor agonists and their combination with sodium-glucose cotransporter-2 inhibitors on myocardial deformation and work index in type 2 diabetes: 1 year follow up

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
I Ikonomidis ◽  
G Pavlidis ◽  
J Thymis ◽  
D Birba ◽  
A Kalogeris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combined Treatment ◽  
Myocardial Strain ◽  
Myocardial Deformation ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Work Index ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose We investigated the effect of novel antidiabetic drugs, glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on myocardial function. Methods A hundred-sixty T2DM patients (age: 58 ± 10years) were randomized to insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40) or their combination (GLP-1RA + SGLT-2i) (n = 40) as add-on to metformin. We measured at baseline and 1 year post-treatment: a) global LV longitudinal strain (GLS), systolic (GLSR) and diastolic (GLSR E) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial work index (GWI), global constructive (GCW) and global wasted work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging. Results After 1 year of treatment, all patients improved GLS, GCS, GRS and pUtwVel (p < 0.05). GLP-1RA or GLP-1RA + SGLT-2i provided a greater increase of GLS (11.5% and 13% vs. 6.8% and 2.3%), GWI (12.7% and 17.4% vs. 3.1% and 2%), GCW (12.3% and 15% vs. 2.2% and 7.8%) and a greater reduction of GWW (38.7% and 41.6% vs. 13.5% and 4.9%) compared with insulin or SGLT-2i, despite a similar HbA1c reduction (p < 0.05 for all comparisons) (Table). Patients under combined treatment with GLP-1RA + SGLT-2i achieved a 2-fold reduction of pTw and a 2-fold increase of pUtwVel than those under each one regimen or insulin (p < 0.05). The dual therapy showed the greatest effect on measured myocardial markers in LVEF < 55% (p < 0.05). Conclusions One year treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i resulted in a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment, independently of glycemic control in T2DM. All patients (n = 160) Insulin (n = 40) GLP-1RA (n = 40) SGLT-2i (n = 40) GLP-1RA + SGLT-2i (n = 40) p-value GLS, % Baseline -16.4 ± 3.7 -16.4 ± 3.5 -16.2 ± 3.5 -17 ± 4 -16 ± 4 0.139 1 year -17.9 ± 3.9 -17.6 ± 4.2 -18.3 ± 3.5 -17.4 ± 3.4 -18.4 ± 4.7 0.003 GWI, mmHg% Baseline 1538 ± 430 1644 ± 416 1510 ± 403 1536 ± 535 1463 ± 362 0.116 1 year 1692 ± 412 1696 ± 377 1730 ± 318 1568 ± 456 1772 ± 499 0.006 pTw, deg Baseline 15.7 ± 6 16 ± 5.1 15.6 ± 5 15.2 ± 6 16.1 ± 8 0.910 1 year 14.6 ± 5.1 15.4 ± 5.4 14.4 ± 5.4 14.7 ± 4.6 14 ± 5 0.034 pUtwVel, deg/s Baseline -104 ± 42 -100 ± 44 -107 ± 41 -101 ± 28 -111 ± 54 0.550 1 year -116 ± 49 -107 ± 55 -114 ± 45 -108 ± 38 -134 ± 61 0.017 Table

scholarly journals Sodium-glucose cotransporter-2 inhibitors and their combination with glucagon like peptide-1 receptor agonists improve endothelial glycocalyx and arterial stiffness in type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Ikonomidis ◽  
G Pavlidis ◽  
J Thymis ◽  
D Birba ◽  
A Kalogeris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pulse Wave ◽  
Combined Therapy ◽  
Post Treatment ◽  
Endothelial Glycocalyx ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background/Introduction Type-2 diabetes mellitus (T2DM) is associated with endothelial and arterial dysfunction. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i)and their combination on endothelial and arterial function of T2DM patients. Methods A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40)as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25μm) using Sideview Darkfield imaging. Increased PBR indicates reduced glucocalyx thickness, b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI) of the aortic pulse wave. Results Twelve months post-treatment, all patients improved PBR, PWV and AI (p<0.05). GLP-1RA, SGLT-2i and their combination showed a greater reduction of PBR, PWV and cSBP than insulin, despite a similar HbA1c reduction (p<0.05). SGLT-2i or combined therapy with GLP-1RA and SGLT-2i showed a greater decrease of PWV (−10.1% and −13% vs. −3.6% and −8.6%) and cSBP (−3% and −5.5% vs. −0.8% and −1.5%)than insulin or GLP-1RA (p<0.05 for all comparisons). GLP-1RA or GLP-1RA+SGLT-2i provided a greater decrease of AI (−42.7% and −48.6% vs. +6.2% vs. −3.8%) compared with insulin or SGLT-2i (Table). The dual therapy showed the greatest effect on measured markers in patients with LVEF <55% (p<0.05). Conclusions Twelve-month treatment with SGLT-2i and its combination with GLP-1RA, showed a greater improvement on arterial elastic properties than GLP1RA or insulin treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

scholarly journals Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

BMJ ◽  
2021 ◽  
pp. m4573 ◽  
Author(s):  
Suetonia C Palmer ◽  
Britta Tendal ◽  
Reem A Mustafa ◽  
Per Olav Vandvik ◽  
Sheyu Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
High Risk ◽  
Meta Analysis ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Randomised Controlled

Abstract Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool ( https://magicevidence.org/match-it/200820dist/#!/ ) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.

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