Is glucose-insulin-potassium (GIK) therapy a legitimate treatment for acute coronary syndrome (ACS) or myocardial infarction (MI)?

GIK Therapy is NOT a Legitimate Treatment for ACS/MI

Based on the most recent and highest quality evidence, glucose-insulin-potassium (GIK) therapy should not be used as a treatment for acute coronary syndrome or myocardial infarction. The 2010 American Heart Association guidelines explicitly state there is little evidence to suggest this intervention is helpful (Class IIb, LOE C), and the 2010 European Society of Cardiology guidelines recommend against its systematic use in diabetic patients undergoing revascularization (Class III, LOE B) 1.

Why GIK Failed in Clinical Practice

The theoretical promise of GIK therapy—metabolic support to ischemic myocardium by enhancing glucose uptake and optimizing cellular metabolism—did not translate into clinical benefit when rigorously tested 2.

The definitive evidence comes from the CREATE-ECLA trial (2005), the largest randomized controlled trial ever conducted on GIK therapy:

• 20,201 patients with STEMI across 470 centers worldwide were randomized to high-dose GIK infusion versus usual care 3
• 30-day mortality was identical: 10.0% in the GIK group versus 9.7% in controls (HR 1.03,95% CI 0.95-1.13, p=0.45) 3
• No benefit was seen in cardiac arrest, cardiogenic shock, reinfarction, or heart failure rates 3
• The lack of benefit was consistent across all subgroups: diabetic vs non-diabetic, with vs without heart failure, early vs late presentation, and with vs without reperfusion therapy 3

A comprehensive meta-analysis of 16 randomized trials spanning 40 years (1966-2008) with 28,374 patients confirmed these findings:

• Overall mortality was 9.6% in both GIK and control groups (OR 1.0,95% CI 0.9-1.1, p=0.9) 4
• Subgroup analysis of high-dose GIK and patients without reperfusion showed no benefit 4

The Critical Timing Problem

Even when GIK was administered in the prehospital setting by paramedics—the earliest possible intervention—the IMMEDIATE Trial showed only marginal and non-significant benefits 5:

• In the overall ACS population, 1-year mortality was 11.6% with GIK versus 13.5% with placebo (HR 0.83,95% CI 0.57-1.23, p=0.36) 5
• Only in the STEMI subgroup did some composite endpoints reach statistical significance, but mortality alone remained non-significant 5

The theoretical requirement that GIK must be initiated within the first hour of symptom onset with successful reperfusion to show benefit is clinically impractical and has not been validated in real-world practice 2.

What Should Be Done Instead

Focus on proven, evidence-based interventions that actually reduce mortality:

• Primary PCI within 120 minutes of first medical contact for STEMI patients (Class I recommendation) 6
• High-intensity statin therapy initiated immediately (Class I, LOE A) 1, 7
• Dual antiplatelet therapy with aspirin plus a potent P2Y12 inhibitor 6
• ACE inhibitors in patients with LVEF ≤40%, heart failure, hypertension, or diabetes (Class I, LOE A) 1
• Beta-blockers in patients with LVEF ≤40% (Class I, LOE A) 1
• Glucose control targeting <11.0 mmol/L (200 mg/dL) while avoiding hypoglycemia in diabetic patients 2, 6

Common Pitfalls to Avoid

• Do not delay proven reperfusion therapy to administer GIK—primary PCI is the gold standard and must be prioritized 6
• Do not confuse glucose control with GIK therapy—maintaining appropriate glucose levels in diabetic patients is important, but this is fundamentally different from administering the GIK infusion protocol 2
• Do not be swayed by older, smaller studies from the 1990s that suggested benefit—the large, modern trials in the reperfusion era definitively showed no benefit 1, 3

The 1999 ACC/AHA guidelines mentioned a promising pilot study of 407 patients, but explicitly stated that "an appropriately sized clinical trial" was needed 1. That trial was conducted (CREATE-ECLA), and it definitively showed no benefit 3.