Glucose-Insulin-Potassium (GIK) has been studied as a potential therapy for acute coronary syndrome for more than 50 years, but despite its effects on mortality and cardiac arrest in patients with ACS remain inconclusive. This is largely because until the IMMEDIATE Trial, previous studies did not follow the approach used in animal studies, which is to administer GIK as soon as possible after the onset of symptoms. Instead, these trials treated patients with GIK once they had an established AMI, hours after symptom onset.


GIK was administered in the IMMEDIATE Trial as an intravenous mixture of 30% dextrose mixed with 80 potassium chloride, and 50 units regular insulin per one-liter and infused over 12 hours.


Mechanism of Action of GIK



Metabolic pathways in the heart and metabolic support provided by glucose-insulin-potassium (GIK). Reprinted from "Glucose-Insulin-Potassium Revived," by A.N Grossman, Circulation 2013; 127:1040-1048.


There appears to be three mechanisms involved in the metabolic benefit of GIK.


GIK confers a protective effect on the myocardium by reducing the levels of circulating free fatty acids (FFAs) found at the onset of symptoms of ACS, and which have an adverse effect on the ischemic and infracting myocardium. The IMMEDIATE Trial demonstrated a reduction of FFAs that was maintained for 12 hours, and associated with significant clinical benefit, including reduction of infarct size.
GIK has been shown to improve ventricular function and improved myocardial glucose uptake.
Glucose-insulin stimulates mitochondrial oxidative metabolism.


All of these mechanisms work together to enhance the metabolic state of the myocardium, and slow the progression of ischemic injury. This in turn lengthens the window of time that injured tissue remains viable and increases the amount of myocardium that can be saved by reperfusion.


If the IMMEDIATE-2 Trial is successful, this will result in a cheap ($400 per patient), safe, and effective treatment for ACS that can save thousands of lives.