|
Nikolaidis et al. 2004 [37]
|
Myocardial ischaemia/reperfusion injury
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GLP-1 (N=10)
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Standard therapy post PPCI (N=11)
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Can a 72-hour infusion of GLP-1 improve global and regional LV function for post infarct myocardial dysfunction following successful PPCI?
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• GLP-1 therapy improved global LVEF (p<0.01)
|
• Small, single-centre, nonrandomized pilot study
|
|
• GLP-1 improved regional (p<0.001) and global (p<0.001) WMSI
|
• Truncated 4-day follow-up window does not allow for extrapolation of results
|
|
• Improvements seen in diabetics and non-diabetics and after anterior and non-anterior MI
|
|
• GLP-1 reduced hospital stay significantly (p<0.02)
|
|
Sokos et al. 2006 [38]
|
Dilated Cardiomyopathy
|
GLP-1 (n=12)
|
Maximum standard therapy (n=9)
|
Can a 5-week subcutaneous infusion of GLP-1 improve both LVEF and functional capacity?
|
• LVEF improved significantly in the GLP-1 arm ((p<0.001) and was unchanged in the control arm
|
• Small, single-centre, open-label, nonrandomised study
|
|
• Type I diabetics excluded but not Type II – potential source of confounding and increased incidence of hypoglycaemia
|
|
• 6MWT distance improved significantly in the GLP-1 arm (p<0.001)
|
|
• Quality of life improved significantly with GLP-1 (p<0.001)
|
• No mention of exact infusion volume – essential in a heart failure cohort
|
|
• Functional improvements seen in diabetics and non-diabetics
|
|
Sokos et al. 2007 [39]
|
CABG surgery
|
GLP-1 (n=12)
|
Standard therapy (n=12)
|
Can peri- and postoperative GLP-1 administration improve haemodynamic recovery after CABG surgery?
|
• No difference in LVEF or cardiac index between the groups
|
• Small numbers despite randomisation
|
|
• Control group required greater use of inotropic and vasoactive infusions
|
• Hypothesis-generating
|
|
• More frequent arrhythmias seen in control group
|
|
Halbirk et al. 2010 [40]
|
Ischaemic cardiomyopathy
|
GLP-1 (n=10 crossover)
|
Saline (n=10 crossover)
|
GLP-1 can improve cardiac function and exercise capacity in non-diabetic patients with heart failure.
|
• Cardiac index and LVEF remained unchanged
|
• Small, single-centre study
|
|
• BNP levels remained unchanged
|
• Active intervention with a 48-hour GLP-1 infusion may have been too short to mediate any improvement in cardiovascular indices
|
|
• Hypoglycaemic events related to GLP-1 treatment were seen in 8 patients
|
|
• Trial protocol only completed in 75% of patients
|
|
Read et al. 2010 [41]
|
Myocardial ischaemia (mediated by dobutamine stress)
|
Sitagliptin (n=14 crossover)
|
Placebo (n=14 crossover)
|
Increased availability of endogenous GLP-1 through DPP-4 inhibition will protect the heart against postischaemic LV dysfunction.
|
• Greater increase in myocardial performance after sitagliptin at peak stress (p=0.0001)
|
• Small study sample
|
|
• Myocardial stunning seen in controls after dobutamine stress whereas sitagliptin maintained LV function
|
• Hypothesis-generating
|
|
• Sitagliptin had a greater beneficial effect on ischaemic vs. nonischaemic LV segments
|
|
Read et al. 2011 [42]
|
Myocardial ischaemia/reperfusion injury
|
GLP-1 (n=10)
|
Saline (n=10)
|
Can GLP-1 protect the heart against ischaemic dysfunction associated with serial 1-minute coronary balloon occlusions during PCI and mitigate myocardial stunning?
|
• GLP-1 infusion improved recovery of LV systolic and diastolic function at 30 minutes post 1-minute coronary balloon occlusion compared with control (p=0.02)
|
• Study too small to assess any clinical endpoints
|
|
• Coronary flow not assessed
|
|
• GLP-1 infusion reduced LV dysfunction after a second 1-minute coronary balloon occlusion compared with control (p=0.01)
|
• Hypothesis-generating
|
|
Read et al. 2012 [43]
|
Myocardial ischaemia (mediated by dobutamine stress)
|
GLP-1 (n=14 crossover)
|
Saline (n=14 crossover)
|
Can GLP-1 protect the heart from ischaemic LV dysfunction and improve myocardial response to dobutamine stress?
|
• Greater increase in LVEF at peak stress during GLP-1 infusion
|
• Small study sample
|
|
• No myocardial stunning seen during GLP-1 infusion
|
• Study not powered to examine clinical end points
|
|
• GLP-1 improved myocardial performance specifically in LV segments subtended by a stenosed vessel and did not in segments receiving an unobstructed blood supply
|
|
Lønborg et al. 2012 [44]
|
Myocardial I/R injury
|
Exenatide (n=85)
|
Saline (n=87)
|
Can exenatide protect against reperfusion injury in STEMI patients following PPCI?
|
• Significantly greater myocardial salvage index in the exenatide group (p=0.003) post PPCI
|
• LVEF after 90 days was not significantly different between the two groups
|
|
• Patients in the exenatide group developed significantly smaller infarcts for an equivalent area at risk (p=0.011)
|
• Study cohort too small to detect a difference in 30-day clinical events
|
|
McCormick et al. 2014 [45]
|
Myocardial ischaemia (mediated by dobutamine stress)
|
Sitagliptin (taken for 4 weeks) (n=19)
|
Standard oral hypoglycaemic agents (n=19)
|
Can chronic DPP-4 inhibition with sitagliptin protect the heart from ischaemic LV dysfunction and improve myocardial response to demand ischaemia during dobutamine stress in Type 2 diabetes patients with CAD
|
• No difference in the rate pressure products at baseline, peak stress, or recovery between the sitagliptin and control scans
|
• Small study sample
|
|
• Cannot exclude degree of variation in individual response to dobutamine during 2 consecutive stress echocardiograms separated by a number of weeks
|
|
• At peak stress there was a greater increase in global ejection fraction following sitagliptin therapy (p<0.0001)
|
|
• At peak stress sitagliptin enhanced regional LV function – seen predominantly in ischaemic segments (p=0.001) whereas there was no effect in non-ischaemic segments (p=0.87)
|
• CAD defined by the presence of a single proximal stenosis >50% in at least 1 epicardial coronary artery – some might argue this level of obstruction would not be haemodynamically significant
|
