Hemodynamic Effects of Glucagon: A Literature Review.

Context: Glucagon's effects on hemodynamic parameters, most notably heart rate and cardiac contractility, are often overlooked. The glucagon receptor is a central target in novel and anticipated type 2 diabetes therapies, and hemodynamic consequences of glucagon signaling have therefore become increasingly important. In this review, we summarize and evaluate published studies on glucagon pharmacology with a focus on clinical hemodynamic effects in humans. Evidence Acquisition: PubMed, Embase, and the Cochrane Library were searched for clinical studies concerning hemodynamic effects of glucagon (no year restriction). Papers reporting effects of a defined glucagon dose on any hemodynamic parameter were included. Reference searches were conducted in retrieved articles. Evidence Synthesis: Hemodynamic effects of glucagon have been investigated mainly in cohort studies of patients suffering from heart failure receiving large glucagon bolus injections. The identified studies had shortcomings related to restricted patient groups, lack of a control group, randomization, or blinding. We identified no properly conducted randomized clinical trials. The majority of human studies report stimulating effects of pharmacological glucagon doses on heart rate, cardiac contractility, and blood pressure. The effects were characterized by short duration, interindividual variation, and rapid desensitization. Some studies reported no measurable effects of glucagon. Conclusions: The level of evidence regarding hemodynamic effects of glucagon is low, and observations in published studies are inconsistent. Actual effects, interindividual variation, dose-response relationships, and possible long-term effects of supraphysiological glucagon levels warrant further investigation.