Table 1 Evidence for GLP-1-mediated cardioprotection in humans

Nikolaidis et al. 2004 [37]

Myocardial ischaemia/reperfusion injury

GLP-1 (N=10)

Standard therapy post PPCI (N=11)

Can a 72-hour infusion of GLP-1 improve global and regional LV function for post infarct myocardial dysfunction following successful PPCI?

• 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