A major problem we have with most diabetes drugs is that while they do lower blood sugars, we don’t have much evidence on whether they actually prolong life and prevent bad outcomes like heart attacks, strokes, cancer, blindness, kidney failure, amputations, and serious infections.
It gets even more complicated. For instance, a given drug may eventually be proven to prolong life by a year via prevention of death from heart disease, while at the same time increasing the risk of spending that last year bedridden from a stroke.
It’s extremely difficult and costly to suss out these issues. It requires large clinical trials wherein half of the PWDs (people with diabetes) are treated with a particular drug, and the other half are treated with “standard therapy.” Five or 10 years later you compare clinical endpoints between the two groups. A couple studies have done this recently.
A blogger I follow, Larry Husten, wrote the following:
But it was the secondary goal of these trials that led to the transformation of the field. Baked into the trial design was the provision that if they were able to establish noninferiority then the trial investigators were permitted to test for superiority. The second phase began when Empa-Reg became the first trial to convincingly show a clear benefit, including a reduction in cardiovascular death and a reduction in hospitalization for heart failure. with empagliflozin (Jardiance, Merck). Then, more recently, the LEADER trial showed a significant reduction in cardiovascular events with liraglutide (Victoza, Novo Nordisk). In both trials nearly all the patients had significant established cardiovascular disease—precisely the population that cardiologists are likely to see.
Click the embedded links above for more details. Even better, read the original research reports if you have the time and knowledge. I support my family with a full-time job taking care of patients, so it will be a while (if ever) before I can dig into this further. (When my book sales make me independently wealthy, I’ll have more time for this!)
Are the LEADER and Empa-Reg trials valid? Yeah, maybe. In an ideal world, other investigators would try to replicate the results with additional clinical trials. Are the published results free of fraud and bias? I don’t know.
Because we don’t know the long-term effects of many of our diabetes drugs, I favor doing as much as possible to control blood sugars with diet, exercise, and weight management.
Stay tuned for future developments.
Steve Parker, M.D.
PS: Just because one drug in a class of drugs reduces bad clinical outcomes, it doesn’t mean all drugs in the class do.
PPS: If it’s hard for you to pronounce empagliflozin and liraglutide, some of my books don’t even have them.