Effects of Glucagon‐Like Peptide‐1 Receptor Agonists, Sodium‐Glucose Cotransporter‐2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12‐Month Treatment
Background 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 patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients w...
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| Published in: | Journal of the American Heart Association Vol. 9; no. 9; p. e015716 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
John Wiley and Sons Inc
05.05.2020
Wiley |
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| ISSN: | 2047-9980, 2047-9980 |
| Online Access: | Get full text |
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| Abstract | Background 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 patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus 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 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure-myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV, global longitudinal strain, global circumferential strain, and global radial strain (
<0.05). GLP-1RA, SGLT-2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction (
<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT-2i (3.1% and 2%). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP-1RA (PWV, 3.6% and 8.6%) (
<0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <55% (
<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 treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either insulin or GLP-1RA and SGLT-2i separately. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03878706. |
|---|---|
| AbstractList | Background 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 patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus 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 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure-myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV, global longitudinal strain, global circumferential strain, and global radial strain (
<0.05). GLP-1RA, SGLT-2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction (
<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT-2i (3.1% and 2%). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP-1RA (PWV, 3.6% and 8.6%) (
<0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <55% (
<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 treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either insulin or GLP-1RA and SGLT-2i separately. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03878706. Background 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 patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus 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 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure‐myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV, global longitudinal strain, global circumferential strain, and global radial strain (P<0.05). GLP‐1RA, SGLT‐2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction (P<0.05). GLP‐1RA or GLP‐1RA+SGLT‐2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT‐2i (3.1% and 2%). SGLT‐2i or GLP‐1RA and SGLT‐2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP‐1RA (PWV, 3.6% and 8.6%) (P<0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <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 treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either insulin or GLP‐1RA and SGLT‐2i separately. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03878706. Background 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 patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus 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 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure-myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV, global longitudinal strain, global circumferential strain, and global radial strain (P<0.05). GLP-1RA, SGLT-2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction (P<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT-2i (3.1% and 2%). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP-1RA (PWV, 3.6% and 8.6%) (P<0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <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 treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either insulin or GLP-1RA and SGLT-2i separately. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03878706.Background 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 patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus 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 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure-myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV, global longitudinal strain, global circumferential strain, and global radial strain (P<0.05). GLP-1RA, SGLT-2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction (P<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT-2i (3.1% and 2%). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP-1RA (PWV, 3.6% and 8.6%) (P<0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <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 treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either insulin or GLP-1RA and SGLT-2i separately. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03878706. |
| Author | Thymis, John Lambadiari, Vaia Kousathana, Foteini Bamias, Aristotelis Parissis, John Ikonomidis, Ignatios Pavlidis, George Birba, Dionysia Iliodromitis, Efstathios Kountouri, Aikaterini Andreadou, Ioanna Balampanis, Konstantinos Kalogeris, Aimilianos Katogiannis, Konstantinos Dimitriadis, George |
| AuthorAffiliation | 3 Laboratory of Pharmacology Faculty of Pharmacy National and Kapodistrian University of Athens Athens Greece 1 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece 2 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece |
| AuthorAffiliation_xml | – name: 2 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – name: 1 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – name: 3 Laboratory of Pharmacology Faculty of Pharmacy National and Kapodistrian University of Athens Athens Greece |
| Author_xml | – sequence: 1 givenname: Ignatios orcidid: 0000-0001-8241-7886 surname: Ikonomidis fullname: Ikonomidis, Ignatios organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 2 givenname: George surname: Pavlidis fullname: Pavlidis, George organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 3 givenname: John surname: Thymis fullname: Thymis, John organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 4 givenname: Dionysia surname: Birba fullname: Birba, Dionysia organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 5 givenname: Aimilianos surname: Kalogeris fullname: Kalogeris, Aimilianos organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 6 givenname: Foteini surname: Kousathana fullname: Kousathana, Foteini organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 7 givenname: Aikaterini surname: Kountouri fullname: Kountouri, Aikaterini organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 8 givenname: Konstantinos surname: Balampanis fullname: Balampanis, Konstantinos organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 9 givenname: John surname: Parissis fullname: Parissis, John organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 10 givenname: Ioanna surname: Andreadou fullname: Andreadou, Ioanna organization: Laboratory of Pharmacology Faculty of Pharmacy National and Kapodistrian University of Athens Athens Greece – sequence: 11 givenname: Konstantinos surname: Katogiannis fullname: Katogiannis, Konstantinos organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 12 givenname: George surname: Dimitriadis fullname: Dimitriadis, George organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 13 givenname: Aristotelis surname: Bamias fullname: Bamias, Aristotelis organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 14 givenname: Efstathios surname: Iliodromitis fullname: Iliodromitis, Efstathios organization: 2nd Department of Cardiology Laboratory of Preventive Cardiology and Echocardiography Department Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece – sequence: 15 givenname: Vaia surname: Lambadiari fullname: Lambadiari, Vaia organization: 2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32326806$$D View this record in MEDLINE/PubMed |
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| Copyright | 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. |
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| Keywords | arterial stiffness glucagon‐like peptide‐1 receptor agonists endothelial glycocalyx sodium‐glucose cotransporter‐2 inhibitors left ventricular function |
| Language | English |
| License | This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
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| Snippet | Background We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i),... Background We investigated the effects of insulin, glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i),... |
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| SubjectTerms | Adult Aged Arterial Pressure - drug effects arterial stiffness Arteries - drug effects Arteries - physiopathology Benzhydryl Compounds - adverse effects Benzhydryl Compounds - therapeutic use Diabetes Mellitus, Type 2 - diagnosis Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - physiopathology Drug Therapy, Combination Endothelial Cells - drug effects Endothelial Cells - metabolism endothelial glycocalyx Female Glucagon-Like Peptide-1 Receptor - agonists Glucosides - adverse effects Glucosides - therapeutic use Glycocalyx - drug effects Glycocalyx - metabolism Greece Humans Incretins - adverse effects Incretins - therapeutic use Insulin - therapeutic use left ventricular function Liraglutide - adverse effects Liraglutide - therapeutic use Male Metformin - therapeutic use Middle Aged Original Research Recovery of Function Sodium-Glucose Transporter 2 Inhibitors - adverse effects Sodium-Glucose Transporter 2 Inhibitors - therapeutic use sodium‐glucose cotransporter‐2 inhibitors Time Factors Treatment Outcome Vascular Stiffness - drug effects Ventricular Function, Left - drug effects |
| Title | Effects of Glucagon‐Like Peptide‐1 Receptor Agonists, Sodium‐Glucose Cotransporter‐2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12‐Month Treatment |
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