How SGLT-2 inhibitors can provide new approach over treatment centered on attaining glycemic control, intensive therapy.
What has been taught in school and reinforced in our minds about diabetes care is to attain glycemic control. Healthcare providers have been indoctrinated with the concept of achieving glycemic control to improve patient outcomes. The Diabetes Control and Complications Trial (DCCT) showed that intensive therapy reduced long-term complications and reduced cardiovascular events. However, the study looks at only patients with type 1 and did not look at those with type 2. Of the many studies, there failed to be a study that showed that glycemic control itself reduces risk of cardiovascular events. Dr. Aaron Vinik talks about a shifting paradigm that has less stringent glycemic goals and alternatively looks to preserve and enhance cardiovascular function.
Dr. Vinik is the Director of Research and the Neuroendocrine Unit Murray Waitzer Endowed Chair for Diabetes Research at the Eastern Virginia Medical School. He is the national leader in basic and clinical neuropathy and has been listed amongst the best physicians in the USA for the past nine years.
Dr. Vinik talks about the shifting paradigm in the care of type 2 diabetes. He brings up an interesting fact that in the ACCORD study, there was a 22 percent increase in sudden death, but these deaths were not caused by cardiovascular events. So what killed the people? Dr. Vinik states, “What killed the people was related to the autonomic dysfunction and the fact that they likely died of an autonomic neuropathy complication with the way you try to intensify glycemic control.” This brought into question the current ideology to be glucocentric, and raised the question: should diabetic care be focused on glucose alone?
The current paradigm has shifted towards a less aggressive approach, assessing individuals for risk, and looking at cardiovascular risk status. Each patient should be assessed individually for their personalized glycemic goals. What has become more accepted are broader A1c targets and less stringent control.
Major new drugs have come out for treating diabetes that have expanded healthcare professionals’ arsenal for managing diabetes. Among those new drugs are the SGLT-2 inhibitors, which target the kidney to inhibit the reabsorption of glucose in the urine. SGLT-2 inhibitors not only reduce blood glucose, but also have a significant reduction in cardiovascular events, which in turn reduces mortality. Does this mean that we can be more aggressive with these new treatments? The short answer is no. This new drug class is allowing us an alternative approach to glycemic control that also takes into consideration cardiovascular risk reduction. According to Dr. Vinik, “The mechanism whereby you reduce the intravascular volume, you decrease the (afterload) on the heart. You decrease the work the heart has to do, [and this] is associated with, a reduction in cardiovascular events, and a reduction in congestive heart failure. So that lo and behold, what sounds as if you are going after aggressive therapy by choosing a drug that will lower glucose, quite by accident, is doing what people have stopped trying to achieve.”
So does this mean that all patients should be on an SGLT-2 inhibitor? It does not necessarily mean that the drug is for everyone. Again, Dr. Vinik emphasizes that it all comes down to the individual and if the drug is right for them. If the patient is prone to urinary tract infections or has a tendency to falls and fracture, the drug may not be for them.
Treatment for diabetes has gone a long way since Dr. Vinik started his career. Technology has progressed enough so that we can now understand the many different mechanisms of disposing glucose. Even now there is much research that will even further our understanding of diabetes and ability to discover novel physiologies and pathophysiology of diabetes.
- The treatment of diabetes is ever changing, shifting from stringent glycemic control to a more individualized approach. Once again, the paradigm of treatment is shifting as new treatment comes out conferring greater benefits.
- Cardiovascular risk is a major issue in diabetic patients. Treatment should revolve around not only glycemic control, but also reducing cardiovascular risk in diabetic patients.
- SGLT-2 inhibitors help reduce the reabsorption of glucose in the kidney, plus. SGLT-2 inhibitors carry additional benefits to the heart and reduce the amount of work required by the heart.
Nathan, David M. “The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview.” Diabetes Care 37.1 (2014): 9-16.
Buse JB, Bigger JT, Byington RP, et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol 2007;99:21i–33i
Eastern Virginia Medical School. “Aaron Vinik”. www.evms.edu
Researched and prepared by Jimmy Tran, Doctor of Pharmacy Candidate LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE