Just a few months ago at the Cardiometabolic Health Conference in Boston, Jay S. Skyler, MD, MACP discussed the effect that even short-term intensive diabetes intervention has, highlighting the differences between three large diabetes drug trials, emphasizing the cardiovascular benefits that some of the new drug therapies display.Dr. Skyler is professor of medicine, pediatrics, and psychology in the division of diabetes and metabolism at the University of Miami Miller School of Medicine.
In the EDIC study, an extension of the DCCT, type 1 patients were followed after having been assigned in the DCCT to either standard care or intensive blood glucose control (with an A1c goal of 6% or less) for a mean of six years.The 20 year follow up in 2005 showed a 42% risk reduction for any cardiovascular outcome for participants in the intensive management group, plus a 57% risk reduction for standard major adverse cardiovascular events.The 30 year data was published in 2016 in Diabetes Care, and the intensive management group saw a continued benefit.There was a 32% risk reduction for adverse cardiovascular events, and a 30% risk reduction for any cardiovascular outcome.One finding that was even more surprising was the 33% reduction in cumulative death for those who had been in the intensive therapy group.In the 20 year follow up of the EDIC continuation of the DCCT trials, in the intensive management group there was a 30% reduction in cardiovascular risk which was a mirror effect from intensive control with the 9.5 year DCCT study.
Another large clinical trial was the STENO-2 study, where 160 Danish patients who chronically had microalbuminuria (protein in the urine)were assigned randomly to either standard care or to intensive therapy, which used medication and behavior modification for an average of eight years.Data published in Diabetologia in August of 2016 showed that 20 years after randomization to the study, patients who were in the intensive intervention group saw a 45% decrease in both the composite cardiovascular endpoint and death from any cause. The participants who were in the intensive intervention group did not maintain their tight control of blood glucose, blood pressure, and cholesterol after the study, but this showed that the early intervention yielded continuing effects.
In the past couple of years, there are some new diabetes drugs that have shown tremendous results. Major cardiovascular outcome clinical trials have given us surprisingly positive information.The EMPA-REG OUTCOME trial in September of 2015 showed that in adults with Type 2 and an established history of cardiovascular disease, the SGLT-2 inhibitor empagliflozin significantly reduced the risk for cardiovascular death and all-cause mortality.In combination with standard care, and not intensive care, this drug decreased the risk of cardiovascular death by 38% versus placebo, with no significant difference in the risk for non-fatal heart attack or stroke.The researchers determined that patients who were treated with empagliflozin saw a 32% decrease in all-cause mortality risk, as well as a 35% reduction in risk for being hospitalized for heart failure.This means that we have a drug that can prevent the risk that most people with diabetes die from, which is cardiovascular death!
We learned from the LEADER trial that the GLP-1 receptor agonist liraglutide decreased the risk for 3-point major adverse cardiovascular events by 13%, for all causes of death by 15%, and for cardiovascular death by 22% versus placebo.It also reduced A1c and body weight.
According to results from the SUSTAIN-6 study, which were presented last fall at the European Association for the Study of Diabetes meeting, the GLP-1 receptor agonist semaglutide significantly lowers the risk for cardiovascular death, non-fatal stroke, or non-fatal heart attack in adults with a diagnosis of type 2 diabetes who have high cardiovascular risk.That makes this the third diabetes drug with a proven cardiovascular benefit!
Dr. Skyler indicated that there are some differences between the three cardiovascular outcome trials.SUSTAIN-6 showed a 26% risk reduction in non-fatal heart attack that did not reach statistical significance; a 39% risk reduction in non-fatal stroke; and a 2% risk reduction in cardiovascular death.He commented that this is the opposite of what was shown in EMPA-REG.In EMPA-REG cardiovascular death was decreased, but there was no impact on non-fatal heart attack or non-fatal stroke.In SUSTAIN, there was no impact on cardiovascular death, but a significant impact on non-fatal heart attack and non-fatal stroke.Dr. Skyler commented, “So, one of the things we have to contemplate is how we think about these composite endpoints, and whether or not they represent the same thing in each case.”
We learn a lot of things from research!It is comforting to know that even if a period of tighter control doesn’t last forever, there are long-term health benefits due to having had a period of tighter control.And given the fact that diabetes confers a higher risk for cardiovascular problems, it’s great to hear that some drugs which are used to control diabetes also provide cardiovascular benefit.We don’t have a cure for diabetes, but if you have to have diabetes, at least this is the best time in history to have it!
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