Many of you who are policymakers decide what is best for your employee’s healthcare in your company or county. As the last two lessons have shown, our understanding of type 2 diabetes has dramatically increased in the last couple of decades. While high sugar levels define type 2 diabetes, they are not the main cause of the dreaded complications of that disease including heart attack, stroke, chronic kidney disease, congestive heart failure, blindness, and nerve damage that lead to premature disability and death. These complications are all due to vascular disease.
Multiple studies have shown that lowering sugar alone with lifestyle measures plus any drug approved for the purpose does not reduce these terrible outcomes. The first embarrassment came in the 1960s. One of the first controlled clinical trials in diabetes rocked the boat. "the findings of this study indicate that the combination of diet and tolbutamide therapy is no more effective than diet alone in prolonging life. Moreover, the findings suggest that tolbutamide and diet may be less effective than diet alone or than diet and insulin at least in so far as cardiovascular mortality is concerned." In other words, more people died when tolbutamide was used to aggressively lower the sugar.
In fact, the entire risk factor approach to type 2 diabetes has failed to lower the rates of these complications. Three major trials in the early 2000s addressed this question: does intensive control of blood sugar to near normal levels compared with standard sugar control reduce the increased risk of vascular disease in people with type 2 diabetes. That assumption had not been proven at the time. In 2008, two of these trials, (ADVANCE) and (VADT), were completed and showed no significant reduction in vascular complications with intensive sugar reduction. A third trial (ACCORD) was stopped early due to the finding of an increased death rate in participants who received very intensive glycemic sugar control to near normal. More people died with intensive sugar lowering using diet, exercise and any drug approved to lower the sugar. The findings of these three major trials led the ADA, with representatives of the American Heart Association (AHA) and the American College of Cardiology (ACC), to relax the recommendations for sugar control in patients with type 2 diabetes. Taken together, these four controlled clinical trials prove conclusively that lowering the sugar using any drug approved for the purpose along with diet and exercise may actually increase the risk of death, the ultimate complication.
Clinical trials have proved that sugar lowering using any medication is not the answer, but now we do know the answer. The Steno 2 clinical trial compared the usual care above—the care that most people receive with optimal medical therapy (OMT) for high-risk patients with type 2 diabetes and chronic kidney disease. The Steno 2 approach did not increase the number of people who died. It substantially reduced mortality and extended life free of heart attacks and strokes by eight years. It provided dramatic benefit for all serious diabetic complications. The Steno 2 trial combined diet, exercise, and a medication protocol that consistently used lisinopril or losartan for hypertension, atorvastatin for cholesterol, metformin for diabetes, and aspirin to prevent clots in these high-risk patients. Patients using the OMT approach had one fourth as many heart attacks, one fifth as many strokes, and one sixth as many people went on to dialysis. They were 70% less likely to be hospitalized for congestive heart failure. This is solid proof that OMT does reduce the most serious complications of type 2 diabetes very dramatically and that is the approach your employees should be counting on.
Not only do we have proof from clinical trials that compare treatments for diabetes, now we understand the science that lowers these complications. We have learned a great deal more about risk factors for vascular disease and the reason that certain treatments are so much more effective. We have already discussed the critical role of the master genetic survival switch. Lowering the risk factor does provide some benefit, but how you lower the risk factor is even more important. Achieving the same blood sugar with metformin compared with other methods lowers your risk of having a heart attack by 39%. Jardiance was developed to lower the sugar in type 2 diabetes. It lowers the progression of chronic kidney disease and heart failure hospitalizations by 30% whether the patient is diabetic or not! The common denominator is that both metformin and Jardiance activate the master genetic survival switch AMPK.
Dr. Milton Packer is one of the most famous heart failure specialists in the world. Here is how he said it: “However, regardless of how their actions are envisioned, it is now critical for physicians to reconceptualize SGLT2 inhibitors (Jardiance) as organ-protective agents rather than glucose-lowering drugs. The antihyperglycemic action of these drugs represents a tiny fraction of their broad portfolio of effects, which (when fully exercised) cause an adaptive reprogramming of stressed cells in a manner that promotes homeostasis and survival.” He is saying this. Lowering the sugar risk factor is important, but that is just a small part of the Jardiance benefit. Jardiance promotes survival in every cell and organ in the body to prolong a healthier, more functional life. Here is the most important part. Jardiance lowers the risk of heart failure or chronic kidney failure whether the patient is diabetic or not. This is the common denominator of all drugs that reduce complications in diabetes or vascular disease. They all directly or indirectly activate the master genetic survival switch AMPK. That includes losartan or lisinopril and eplerenone or spironolactone for hypertension, statins for cholesterol, metformin for diabetes, and aspirin to prevent clotting. On the other hand, drugs like insulin and the tolbutamide that increases insulin levels in the blood inactivate the master genetic survival switch AMPK. That is how it is all tied together.
If your program for diabetes quality improvement is not using systems and protocols, they are almost certainly not improving the care for your employees with diabetes. It is essential that you do the analysis that proves the solution you are using improves diabetic outcomes and reduces the cost of care. You can’t know what you are getting without looking at the numbers. If you are the adult setting healthcare policy in your own household, these same facts apply to you.