We conducted a meta-analysis of the existing literature of the therapeutic effects of using GLP-1 agonists to improve the metabolism of the failing heart. Animal studies showed significant improvement in markers of cardiac function, such as left ventricular ejection fraction (LVEF), with regular GLP-1 agonist infusions. In clinical trials, the potential effects of GLP-1 agonists in improving cardiac function were modest: LVEF improved by 4.4% compared to placebo (95% C.I 1.36–7.44, ). However, BNP levels were not significantly altered by GLP-1 agonists in heart failure. In two trials, a modest increase in heart rate by up to 7 beats per minute was noted, but meta-analysis demonstrated this was not significant statistically. The small number of studies plus variation in the concentration and length of the regime between the trials would limit our conclusions, even though statistically, heterogeneity chi-squared tests did not reveal any significant heterogeneity in the endpoints tested. Moreover, studies in non-diabetics with heart failure yielded conflicting results. In conclusion, the use of GLP-1 agonists has at best a modest effect on ejection fraction improvement in heart failure, but there was no significant improvement in BNP levels in the meta-analysis. 1. Introduction Heart failure (HF) is defined as “a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood” [1]. HF is a major public health issue, with a prevalence of over 5.8 million in the USA, and over 23 million (and rising) worldwide. The lifetime risk of developing HF is one in five [2]. Despite advances in treatment, the number of deaths from heart failure has increased steadily and only one quarter to one-third of people with heart failure survive 5 years after admission [3]. The cause of heart failure has shifted in the last two decades: in the late 1970s, rheumatic valvular disease was the primary cause, nowadays the leading cause is ischemic heart disease [4]. A deficit in the “pump” function as cause of signs or symptoms attributed to HF, or systolic dysfunction, is frequently well diagnosed due to widespread availability of echocardiography but, an increased left ventricular (LV) “stiffness,” or diastolic dysfunction, is often missed. To further complicate matters, the two components—systolic and diastolic dysfunction—often coexist. Some studies [5, 6] reported that isolated diastolic dysfunction could be responsible for up to 50% of heart failure admissions (often labelled as
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