Just over 15 years ago, I attended a medical conference and heard a brilliant presentation by Dr. David Lefer. He had created an experimentally-induced heart attack in mice by tying off a heart artery for 30 minutes and then releasing it. That creates an area of dead heart muscle that is very consistent. If a single dose of a statin was given prior to the heart attack, the amount of damage was reduced by about half. A few months later, I was on my way to another conference, and shared a cab with Dr. Lefer. I had learn a lot about metformin by that time, and suggested it would produce a similar result.
A couple of years later, Dr. Lefer contacted me and said, “it worked.” In non-diabetic mice, 1/286th of the maximum metformin dose for diabetes given 18 hours prior to tying off the artery reduced the extent of heart muscle damage by 62%. Metformin produced this result by activating AMPK and increasing nitric oxide activity (the active ingredient in nitroglycerin.) This very small, single dose of metformin produced that remarkable result by interfering with the molecular signaling that damages the heart. It had nothing to do with the blood sugar level.
As you can see from the diagram, all green box interventions do the same thing in humans. Not surprisingly, metformin reduces the risk of heart attack by 39% compared with other medications achieving the same glucose level. Here is the most remarkable thing. Patients on an optimal medical therapy protocol for type 2 diabetes that combines atorvastatin, metformin, lisinopril, and an aspirin—all switch on AMPK and switch off mTOR— have one fourth as many heart attacks as patients in usual care, the care that most of us receive. It is past time to make optimal medical therapy (OMT) more widely available and you can help. It is time to start teaching our students about OMT and developing the teams to deliver the OMT product.
I find this fascinating. After years on steroids I live in the "pre-diabetes" world which include metofrmin daily. The more I read of your posts the happier I am when I have to take that med everyday. Thanks for this post!