You Can’t Rely on Industry-sponsored Research on Evidence-based Treatments for Chronic Disease
This article was just published in the Journal of the American Medical Association this week. It claims to answer this question. What is the contemporary pattern of evidence-based pharmacotherapy use among a real-world population of US patients with type 2 diabetes and atherosclerotic cardiovascular disease?
The article does provide some valuable information. These patients in the study had diabetes and they already had artery disease. They were very high risk. Because of these characteristics, all these patients should be on a high intensity statin. Fewer than 60% were on a statin at all. Only 27% were receiving a high-intensity statin. Only 46% of these patients were on an ACE inhibitor like lisinopril are an angiotensin receptor blocker (ARB) like losartan. Those are good things to know. The problems begin when the authors begin to discuss diabetes medications.
Four percent of patients received a GLP-1 drug like liraglutide. Three percent received an SGLT2 inhibitor like empagliflozin. Fewer than five percent received all three evidence-based therapies-ACEARB, statin, and GLP-1 or SGLT2 inhibitor. I agree these are huge gaps in care for very high-risk patients, but there is an equally disturbing problem. Most remarkably, they did not include metformin as a therapy with a proven cardiovascular benefit. They did report that metformin was only prescribed in 37% of these patients.
There is a mountain of evidence supporting the critical role of metformin in preventing vascular events in diabetes. Since 1998, these reports have consistently shown that metformin reduces the risk of dying from heart disease by 30-40%. The UKPDS study showed that metformin reduced the risk of heart attack by 39% in 1998. Patients with diabetes on metformin in the UK live a little longer than matched normal individuals without diabetes. Like the SGLT2 inhibitors, metformin switches on AMPK and switches off mTOR. Metformin has similar evidence-based benefits as empagliflozin, an SGLT2 inhibitor. Metformin cost $4 a month. Empagliflozin costs $550 dollars a month. Metformin first, regardless of the blood sugar level, is the first medication to use for type 2 diabetes.
Even so, the authors are ignoring the main point. Empagliflozin reduces hospitalizations for chronic kidney disease and heart failure by 30%. Optimal medical therapy that combines evidence-based treatments has a much bigger impact. It reduces progression to dialysis six-fold compared with usual care. That is the key. Combine exercise, intermittent fasting, carbohydrate restriction, an ace inhibitor or an angiotensin receptor blocker, a statin, metformin, and spironolactone or eplerenone as appropriate to achieve an even greater impact. It is not which medication is best. It is the combination of disease modifying interventions that has a huge impact.
Why did the authors omit metformin as an evidence-based treatment in type 2 diabetes? I think it is because of conflicts of interest. Two of the authors were drug company employees. Most of the authors had extensive financial relations with the companies involved and the drug companies funded the study. Metformin is an evidence-based treatment. This article will confuse providers and I am deeply suspicious of the conflicts of interest. What do you think?