Effects of glucagon-like peptide-1 agents on left ventricular function: Systematic review and meta-analysis

Figures & data

Figure 1. Flow chart of search strategy and results.

Table I. Characteristics of 14 clinical controlled trials evaluating the cardiovascular effects of GLP-1 administration.

Author	Year	Study design	Inclusion criteria	Follow-up	n^a	Age	Administration
Read PA et al. [23]	2012	random prospective	CAD and normal EF	immediately	7/7	63.7 ± 8.7	GLP-1, 1.2 pmol/kg/min for 30 min
Nielsen R et al. [20]	2012	random prospective	CAD, HF, and EF < 40%	immediately	5/6	60 ± 3	GLP-1, 0.7 pmol/kg/min for 48 h
Gejl M et al. [15]	2012	random prospective	T2DM without CAD	immediately	4/4	58.3 ± 1.7	Exenatide, 0.066 pmol/kg/min for 260 min
Read PA et al. [22]	2011	random prospective	CAD and normal EF	immediately	10/10	66.3 ± 9.9	GLP-1, 1.2 pmol/kg/min for 30 min
Lønborg J et al. [19]	2011	random prospective	STEMI	3 months	85/87	63 ± 10	Exenatide, 0.12 mg/min for 6 h
Halbirk M et al. [13]	2010	random prospective	HF and EF < 40% without DM	48 hours	10/10	61 ± 3	GLP-1, 1 pmol/kg/min for 48 h
Read PA et al. [24]	2010	random prospective	CAD and normal EF	immediately	7/7	63.6 ± 7.4	Sitagliptin, 100 mg single orally
Gill A et al. [16]	2010	random prospective	T2DM	12 weeks	22/23	57 ± 11	Exenatide, 5 μg BID for 12 weeks
Bharucha AE et al. [5]	2008	random prospective	healthy volunteers	90 minutes	7/8	34 ± 3	GLP-1, 1.2 pmol/kg/min for 90 min
Sokos GG et al. [25]	2007	random prospective	CAD and EF > 35%	60 hours	10/10	65.1 ± 8.8	GLP-1, 1.5 pmol/kg/min for 60 h
Sokos GG et al. [9]	2006	retrospective	HF and EF < 40%	4 weeks	12/9	61 ± 4	GLP-1, 1.25 pmol/kg/min for 4 weeks
Nikolaidis LA et al. [12]	2004	retrospective	CAD and EF < 40%	72 hours	10/11	58 ± 3	GLP-1, 1.5 pmol/kg/min for 72 h
Nystrom T et al. [21]	2004	random prospective	T2DM with CAD	immediately	12/10	61 ± 3	GLP-1, 2 pmol/kg/min for 120 min
Toft-Nielsen MB et al. [27]	1999	random prospective	T2DM	immediately	6/6	59.0 ± 2.8	GLP-1, 2.4 pmol/kg/min for 48 h

CAD = coronary artery disease; EF = ejection fraction; HF = heart failure; STEMI = ST, segment elevation myocardial infarction; T2DM = Type 2 diabetes mellitus.

^aGLP-1 group versus control group.

Table II. Quality assessment of randomized clinical studies inclusion.

Study	Allocation Concealment	Blinding	Randomized generator	Lost to follow-up	Scores
Read PA [23]	No	No	No	Yes	B
Nielsen R [20]	No	Yes	Yes	Yes	A
Gejl M [15]	No	Yes	No	Yes	B
Read PA [22]	No	Yes	No	Yes	B
Lønborg J [19]	No	Yes	Yes	Yes	A
Halbirk M [13]	No	Yes	No	Yes	B
Read PA [24]	No	Yes	No	Yes	B
Gill A [16]	No	Yes	No	Yes	B
Bharucha AE [5]	No	Yes	No	Yes	B
Sokos GG [25]	No	Yes	Yes	Yes	A
Nystrom T [21]	No	Yes	No	Yes	B
Toft-Nielsen MB [27]	No	Yes	No	Yes	B

Figure 2. Forest plot showing results from meta-analysis of trials reporting hemodynamic parameters treated with GLP-1 relative to control.

Figure 3. Forest plot showing results from meta-analysis of trials reporting global left ventricular performance.

Figure 4. Forest plot showing results from meta-analysis of trials reporting regional left ventricular contractile capacity.

Figure 5. Forest plot showing results from meta-analysis of trials reporting clinical manifestation.

Figure 6. Publication bias. If publication bias is not present, funnel plot is expected to be roughly symmetrical.

Read PA, Khan FZ, Dutka DP. Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart. 2012;98:408–13.

 PubMed Web of Science ®Google Scholar

Nielsen R, Wiggers H, Halbirk M, Bøtker H, Holst JJ, Schmitz O, et al. Metabolic effects of short-term GLP-1 treatment in insulin resistant heart failure patients. Exp Clin Endocrinol Diabetes. 2012;120:266–72.

 Google Scholar

Gejl M, Søndergaard HM, Stecher C, Bibby BM, Møller N, Bøtker HE, et al. Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. J Clin Endocrinol Metab. 2012;97:E1165–9.

 PubMed Web of Science ®Google Scholar

Read PA, Hoole SP, White PA, Khan FZ, O’Sullivan M, West NE, et al. A pilot study to assess whether glucagon-like peptide-1 protects the heart from ischemic dysfunction and attenuates stunning after coronary balloon occlusion in humans. Circ Cardiovasc Interv. 2011;4:266–72.

 PubMed Web of Science ®Google Scholar

Lønborg J, Vejlstrup N, Kelbæk H, Bøtker HE, Kim WY, Mathiasen AB, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;33:1491–9.

 PubMed Web of Science ®Google Scholar

Halbirk M, Nørrelund H, Møller N, Holst JJ, Schmitz O, Nielsen R, et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol. 2010;298:H1096–102.

 PubMedGoogle Scholar

Read PA, Khan FZ, Heck PM, Hoole SP, Dutka DP. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging. 2010;3:195–201.

 PubMed Web of Science ®Google Scholar

Gill A, Hoogwerf BJ, Burger J, Bruce S, Macconell L, Yan P, et al. Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study. Cardiovasc Diabetol. 2010;9:6.

 PubMed Web of Science ®Google Scholar

Bharucha AE, Charkoudian N, Andrews CN, Camilleri M, Sletten D, Zinsmeister AR, et al. Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans. Am J Physiol Regul Integr Comp Physiol. 2008;295:R874–80.

 Google Scholar

Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern GJ Jr, Maher TD, et al. Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol. 2007;100:824–9.

 PubMed Web of Science ®Google Scholar

Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail. 2006;12:694–9.

 PubMed Web of Science ®Google Scholar

Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004;109:962–5.

 PubMed Web of Science ®Google Scholar

Nyström T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004;287:E1209–15.

 PubMed Web of Science ®Google Scholar

Toft-Nielsen MB, Madsbad S, Holst JJ. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care. 1999;22: 1137–43.

 PubMed Web of Science ®Google Scholar