1. Got GIK? Darren K McGuire, MD Senior Fellow
Duke Clinical Research Institute
Durham, NC

2. GIK
Where it all began
1912-Cane sugar suggested as a therapy for cardiovascular disease
1914-Mechanistic explanation of the benefit of glucose therapy for heart disease reported
1933-Insulin/glucose suggested as a therapy for angina pectoris and heart disease
1960’s-Sodi-Pallares, et al introduced GIK for the treatment of AMI
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3. GIK
History
1962-Demetrio Sodi-Pallares introducs “Polarizing Therapy” for acute MI
Based on Ko/Ki perturbation with MI
Insulin/Glucose used to facilitate “passive” entry of K+ into cells
Recent knowledge suggests insulin is the therapeutic agent.
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4. GIK Limitations of trials
Most obvious limitation is the lack of power of each of the trials reported
Confounding this are:
inconsistency in dosing of GIK
inconsistency of initiation (12-48 hrs)
inconsistency of termination of infusion (6 hr-14 d)
most excluded age >75
Pre-thrombolytic era with poor outcomes
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5. GIK GIK trials meta-analysis
Mortality Rate (%)
Year
Study N
GIK
Control
1977 Heng
1978 Stanley
1979 Rogers
1987 Satler
1965 Mittra
1967 Pilcher
1968 Pentecost
1968 MRC
1971 Hjermann
All Patients
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Fath-Ordoubadi, F and Beatt, KJ, Circulation 1997;96:

6. GIK GIK trials meta-analysis 2 Odds Ratio (99% CI) GIK Better
Year
Study
GIK Better
Placebo Better
1977 Heng
1978 Stanley
1979 Rogers
1987 Satler
1965 Mittra
1967 Pilcher
1968 Pentecost
1968 MRC
1971 Hjermann
Total
p=0.004; 95% CI
0.5 1
1.5 2

7. GIK Questions and hurdles
Will this apparent benefit persist given today’s modern therapies?
Because it is a non-proprietary therapy, it has been ignored by the pharmaceutical industry and many opinion leaders.
GIK is not mentioned as a potential therapy option in the current ACC/AHA guidelines.
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8. GIK Use in clinical practice
“In the developing world, in non-western societies, it is a little bit more of an issue if an effective therapy like GIK can be used in addition to, or even instead of thrombolytic or other expensive therapies.”
Darren K McGuire, MD
Senior Fellow
Duke Clinical Research Institute
Durham, NC
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9. GIK ECLA GIK pilot study Estudios Cardiológicos Latinoamérica
Safety and feasibility study
High-dose GIK vs Low-dose GIK vs Std Rx
407 patients enrolled 24 hours of ACS
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Díaz, R, et. al. Circulation 1998;98:

10. Ventricular Fibrillation
GIK
ECLA GIK: In hospital events
Death
Overall
Reperfused
CHF(Killip>2)
Overall
Reperfused
Ventricular Fibrillation
Overall
Reperfused
Death/CHF/Vfib
Overall
Reperfused
0.1 1 10
GIK Better
Std Rx Better

11. GIK ECLA GIK: Conclusions Trends favor GIK added to “modern” therapy
Benefit appears to be complementary to reperfusion therapies
Warrants further investigation in a full-scale clinical trial

12. GIK ECLA GIK-2 Open-label randomized multi-center study
Comparison of GIK + Std Rx vs Std Rx alone for ST-elevation MI
300 Centers planned:
Latin America, North America, Europe, Australia, New Zealand, South Africa, and Asia
10,000 patients planned
90% power to detect 20% difference at =0.05 in Primary Endpoint: 30-day Mortality
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13. GIK Enrollment challenge
Only 4 US sites have joined on despite the simplicity of the trial and the minimal resources required to participate.
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14. GIK Joining ECLA GIK-2 Darren McGuire Duke Clinical Research Institute
P.O. Box 17969
Durham NC 27715
Tel:
Web:
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15. GIK Resource issues Requires: Multiple IV drips (G/I/K)
Frequent glucose and potassium monitoring
Increased nursing care requirements
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