In the initial VADT trial, severe hypoglycemia occurred nearly three times more commonly in the intensively treated group, compared with the standard therapy group. Severe hypoglycemia was defined as an episode of low blood glucose that was accompanied by confusion requiring assistance from another person or loss of consciousness. In related analyses, the hazard ratio for CV events, CV mortality, and overall mortality with severe hypoglycemia within the preceding 3 months was also increased. “So this is a consistent finding across multiple studies of the danger of severe hypoglycemia occurring during your efforts to improve glucose lowering,” Dr. Reaven said. “Interestingly, it appears that the risk for CVD events following severe hypoglycemia increases with higher baseline CV risk, based on the United Kingdom Prospective Diabetes Study 10-year CV risk score. So, how great your risk is begins to influence how well you do after severe hypoglycemia.”
In a separate stratified analysis of VADT data, the risk for CVD after severe hypoglycemia was more prominent in the standard treatment group, compared with the intensive treatment group. “There’s nearly a sevenfold increased risk for all-cause mortality following severe hypoglycemia in the preceding 3 months,” he said. “The same pattern is present for cardiovascular mortality and, somewhat, for cardiovascular events, although not statistically significant. The association between symptomatic, severe hypoglycemia and mortality in type 2 diabetes was seen in the ACCORD [Action to Control Cardiovascular Risk in Diabetes] population as well.”
A subset of patients in the VADT study showed that individuals in the standard therapy group who had a prior serious hypoglycemic episode actually had greater coronary calcium progression during the study, compared with the intensively treated group (P = .02; Diabetes Care 2016;39[3]:448-54). “One possibility is that serious hypoglycemia contributed to the development of atherosclerosis in this group,” Dr. Reaven said. “This held true when one examined high and lower glucose levels on average in the study. Those individuals that had A1c levels of 7.5% or above were the ones that appeared to show coronary calcium progression during the study following episodes of severe hypoglycemia, whereas it did not appear to be an issue among those with good glucose control. Another finding was that severe hypoglycemia is associated with increased glucose variability from office visit to office visit.”
He concluded his remarks by noting that being “glucose centric” is not the right approach to treating patients with diabetes. “Other risk factors may offer bigger and more rapid benefits,” he said. “The benefits of glucose lowering are likely most relevant in type 1 diabetes and in early type 2 diabetes, and the benefits of glucose lowering on vascular disease appear to take a long time. Avoid severe hypoglycemia, especially in older patients with type 2 diabetes. This last point may be particularly relevant for those in poor control.”
Dr. Reaven reported having no relevant financial disclosures.
dbrunk@frontlinemedcom.com