Effect of Glucagon-Like Peptide-1 (GLP-1) on Glycemic Control and Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting

doi:10.1016/j.amjcard.2007.05.022

The American Journal of Cardiology

Volume 100, Issue 5, 1 September 2007, Pages 824-829

https://doi.org/10.1016/j.amjcard.2007.05.022 Get rights and content

Increasing evidence suggests that tight glycemic control improves clinical outcomes after coronary artery bypass grafting (CABG). However, the risk for hypoglycemia with insulin often results in less aggressive glycemic control. Glucagon-like peptide–1 (GLP-1) is a naturally occurring peptide whose insulinotropic effects are predicated on the glucose concentration, minimizing the risk for hypoglycemia. This study was conducted to examine whether perioperative treatment with GLP-1 would affect glycemic control and improve hemodynamic recovery after CABG. Twenty patients with coronary heart disease and preserved left ventricular function who were scheduled to undergo CABG were randomized to receive standard therapy at the discretion of the surgeon or treatment with GLP-1 (1.5 pmol/kg/min) as a continuous infusion beginning 12 hours before CABG and continuing for 48 hours. Perioperative hemodynamics, the left ventricular ejection fraction, plasma glucose, and requirements for insulin drips and inotropic support were monitored. There were no differences between groups in the preoperative, postoperative, or 7-day left ventricular ejection fraction (GLP-1 61 ± 4%, control 59 ± 3%) or cardiac index at 18 hours (GLP-1 3.0 ± 0.2 L/min/m², control 3.3 ± 0.4 L/min/m²). However, the control group required greater use of inotropic and vasoactive infusions during the 48 hours after the operation to achieve the same hemodynamic result. There were also more frequent arrhythmias requiring antiarrhythmic agents in the control group. GLP-1 resulted in better glycemic control in the pre- and perioperative periods (GLP-1 95 ± 3 mg/dl, control 140 ± 10 mg/dl, p ≤0.02), with 45% less insulin requirements to achieve the same glycemic control in the postoperative period (GLP-1 139 ± 4 mg/dl, control 140 ± 3 mg/dl). In conclusion, the perioperative use of GLP-1 achieves better glycemic control and comparable hemodynamic recovery without the requirements for high-dose insulin or inotropes.

Section snippets

Methods

The study was designed as a single-center, randomized, double-blind, placebo-controlled pilot study to determine the safety and efficacy of GLP-1 treatment compared with standard insulin therapy. Men and women aged >18 years who consented and were scheduled for nonemergent CABG were eligible for enrollment. The patients were required to have LVEFs ≥35% as determined by echocardiography before surgery. Patients who required emergent surgery or whose surgery included valve repair or replacement,

Results

Table 1 summarizes the characteristics of the patient populations randomized to the 2 strategies. There were no significant differences between the groups in terms of age, gender, history of hypertension, diabetes, or smoking. There were no differences in surgical features, such as the number of distal anastomoses, cardiopulmonary bypass time, or aortic cross clamp time. Notably, although the total hospital stay was similar, GLP-1-treated patients showed a trend toward shorter intubation times

Discussion

In the present study, we investigated the effects of GLP-1 on glycemic control and hemodynamic recovery in patients with normal LVEFs who underwent CABG. We observed that GLP-1 infusion was associated with reduced pre- and perioperative plasma glucose levels and reduced requirements for insulin infusion to achieve euglycemia in the postoperative period compared with standard treatment. Notably, there were no differences in postoperative hemodynamic parameters or LVEFs in the 2 groups, but GLP-1

Acknowledgments

We would like to thank Diane Vido for her statistical analysis of the data, Carol Stolarski for her performance of metabolic assays, and Nick Kleissas, RPh, for his help with infusion preparation and patient randomization.

References (21)

D. Elahi et al.
The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects
Regul Pept
(1994)
G.G. Sokos et al.
Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure
J Card Fail
(2006)
R.M. Lang et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J Am Soc Echocardiogr
(2005)
A.P. Furnary et al.
Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting
J Thorac Cardiovasc Surg
(2003)
C.A. Estrada et al.
Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting
Ann Thorac Surg
(2003)
W.A. Lell et al.
Glucose-insulin-potassium infusion for myocardial protection during off-pump coronary artery surgery
Ann Thorac Surg
(2002)
H.L. Lazar et al.
Glucose-insulin-potassium solutions enhance recovery after urgent coronary artery bypass grafting
J Thorac Cardiovasc Surg
(1997)
T. Velissaris et al.
A prospective randomized study to evaluate stress response during beating-heart and conventional coronary revascularization
Ann Thorac Surg
(2004)
J.H. Levy et al.
Inflammatory response to cardiopulmonary bypass
Ann Thorac Surg
(2003)
A. Flint et al.
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans
J Clin Invest
(1998)

There are more references available in the full text version of this article.

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Whether an antidiabetic drug, glucagon-like peptide-1 receptor agonist (GLP-1RA), could improve the prognosis of heart failure and cardiac function remains controversial. We conducted a systematic review and meta-analysis of randomized controlled trials to explore the influence of GLP-1RAs on heart failure in patients regardless of diabetes diagnosis.
Literature in English from the PubMed, EMBASE, and Cochrane Library databases was searched from inception to July 2022. The study aim was to identify published, randomized, placebo-controlled trials testing GLP-1RAs in patients with or without diabetes. Outcomes were heart failure hospitalization, cardiac function, and structure measures.
Twenty-two randomized controlled trials involving 61,412 patients are included in the meta-analysis. Overall, compared with the placebo group, GLP-1RA treatment could not significantly decrease heart failure hospitalization in patients with a history of heart failure (hazard ratio [HR], 1.07; 95% CI, 0.91 to 1.25; P = 0.422). Six-minute walking test distances (WMD, 19.08 m; 95% CI, 4.81 to 33.36; P = 0.01), E-wave (SMD, –0.40; 95% CI, –0.60 to –0.20; P < 0.001), early diastolic to late diastolic velocities ratio (WMD, –0.10; 95% CI, –0.18 to –0.02; P = 0.01), mitral inflow E velocity to tissue Doppler e′ ratio (WMD, –0.97; 95% CI, –1.54 to –0.41; P < 0.001), and E-wave deceleration time (WMD, –9.96 milliseconds; 95% CI, –18.52 to –1.41; P = 0.02) increased significantly after administration of GLP-1RAs. However, GLP-1RAs do not significantly influence N-terminal pro–B-type natriuretic peptide levels (WMD, –20.02 pg/mL; 95% CI, –53.12 to 13.08; P = 0.24), Minnesota Living with Heart Failure Questionnaire quality of life scores (WMD, –1.08; 95% CI, –3.99 to 1.84; P = 0.47), or left ventricular ejection fractions (WMD, –0.37%; 95% CI, –1.19 to 0.46; P = 0.38).
GLP-1RAs did not reduce heart failure readmissions in patients with a history of heart failure and elevated N-terminal pro–B-type natriuretic peptide levels. Thus, the prognosis of heart failure was not improved, although GLP-1RAs did significantly improve left ventricular diastolic function in patients. PROSPERO identifier: CRD42021226231.
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Citation Excerpt :
In animal models, intravenous infusion of GLP-1 receptor agonists improved left ventricular contractility, improved functional recovery and cardiomyocyte viability, and reduced the risk of heart attack and atherosclerotic deposits [42]. In human models, GLP-1 receptor agonists also in cardioprotective effects including reduction of arrhythmia risk, improvement of left ventricular function and endothelial function in patients with and without diabetes, and also in surgical revascularisation, heart failure, and coronary heart disease [39,41,43,44]. The most important mechanism of GLP-1 receptor agonists in lowering blood pressure is their influence on the secretion of atrial natriuretic hormone (ANP) and the consequent vasodilation, natriuresis and diuresis [45].
Prevention of cardiovascular events and regression of atherosclerotic changes are the primary aims of preventive cardiovascular medicine. Arterial thrombosis is caused by endothelial dysfunction, which disrupts vascular haemostasis. Glucagon-like peptide 1 (GLP-1) receptor agonists have been initially used as glucose lowering agents, but over time have been used for other indications due to their cardiorenal benefit, as well as their benefit in the regression of atherosclerosis process. The aim of this paper is to present the benefits of GLP-1 receptor agonists in the prevention of atherosclerotic changes, in the preservation of brain vascular function, and to show the possible role in the treatment of neurodegenerative diseases.
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Hyperglycaemia in people with and without diabetes admitted to the hospital is associated with a substantial increase in morbidity, mortality, and health-care costs. Professional societies have recommended insulin therapy as the cornerstone of inpatient pharmacological management. Intravenous insulin therapy is the treatment of choice in the critical care setting. In non-intensive care settings, several insulin protocols have been proposed to manage patients with hyperglycaemia; however, meta-analyses comparing different treatment regimens have not clearly endorsed the benefits of any particular strategy. Clinical guidelines recommend stopping oral antidiabetes drugs during hospitalisation; however, in some countries continuation of oral antidiabetes drugs is commonplace in some patients with type 2 diabetes admitted to hospital, and findings from clinical trials have suggested that non-insulin drugs, alone or in combination with basal insulin, can be used to achieve appropriate glycaemic control in selected populations. Advances in diabetes technology are revolutionising day-to-day diabetes care and work is ongoing to implement these technologies (ie, continuous glucose monitoring, automated insulin delivery) for inpatient care. Additionally, transformations in care have occurred during the COVID-19 pandemic, including the use of remote inpatient diabetes management—research is needed to assess the effects of such adaptations.
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Cardiac surgery with cardiopulmonary bypass (CPB) is associated with gut barrier dysfunction. Gut barrier dysfunction might be estimated non-invasively by lipopolysaccharide (LPS) plasma concentration. Glucagon-like peptide-1 (GLP-1) is a gut secreted hormone that is a potential marker of mucosal integrity. Our objective was to evaluate GLP-1 as a peri-operative marker of gut barrier dysfunction in patients undergoing cardiac surgery with CPB.
GLP-1, intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide were assayed: at induction, after CPB and 24 h after admission in the intensive care unit. The primary end-point was peri-operative lipopolysaccharide concentration (LPS concentration at those 3 time points).
Seventy-two patients were included in the present analysis. The highest measured post-operative GLP-1 concentration was in the sample taken 24 h after admission to intensive care, which was associated with peri-operative lipopolysaccharide plasma concentration. Patients who had the highest GLP-1 concentrations at 24 h experienced more severe inflammation and worse clinical outcomes.
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: This work has been supported in part by The Pittsburgh Foundation, Pittsburgh, Pennsylvania. Dr. Sokos received salary support for this project from the American College of Cardiology Merck Fellowship Award, Bethesda, Maryland.

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Coronary artery diseaseEffect of Glucagon-Like Peptide-1 (GLP-1) on Glycemic Control and Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting

Section snippets

Methods

Results

Discussion

Acknowledgments

Regul Pept

J Card Fail

J Am Soc Echocardiogr

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans

J Clin Invest

Coronary artery disease
Effect of Glucagon-Like Peptide-1 (GLP-1) on Glycemic Control and Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting