Diabetes Research Finds Hypoglycemia Increases Death Risk Four-Fold

Researcher presented at the European Association for the Study of Diabetes 2017 (EASD) in Lisbon, Portugal, highlighted the significant risk of death caused by hypoglycemia among patients with diabetes.

The findings were part of the DEVOTE trial, a multinational, double-blinded clinical trial that observed the efficacy of Tresiba (insulin degludec; Novo Nordisk) in more than 7500 patients with type 2 diabetes. DEVOTE is the first cardiovascular outcomes trial comparing two basal insulins. Participations included patients with high risk of cardiovascular disease who were being provided care to reduce cardiovascular risks. The primary findings of DEVOTE showed that Tresiba does not increase cardiovascular risks any more than traditional insulin glargine U100. 

Secondary findings reported in this presentation were related to the risk reduction of hypoglycemia. 

“Episodes of severe hypoglycaemia are not only distressing for patients and potentially dangerous, they are also associated with an increased risk of death,” Bernard Zinman, MD, of the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, said in a press release. “These results highlight the importance of maintaining low variability in blood sugar levels and reducing the risk of severe hypoglycaemia when treating people with type 2 diabetes.”

The researchers showed that patients with diabetes who experience severe hypoglycemia events have a significantly increased risk for death, with risk increasing four times higher at 15 days after an event and more than doubling at any time after an event. Furthermore, the researchers found that fluctuations in blood sugar levels are also associated with a higher risk of death among those with type 2 diabetes.

Furthermore, the researchers—from Novo Nordisk—concluded that Tresiba would reduce the risk of death by reducing the risk for severe hypoglycemia by 40%—compared to patients on Lantus (insulin glargine U100; Sanofi). Furthermore, Tresiba cut the risk for nocturnal hypoglycemia by 53% compared to Lantus. 

“Day-to-day fasting glycaemic variability was significantly associated with severe hypoglycemia and all-cause mortality,” Dr Zinman concluded in his presentation at EASD 2017. “These data support clinical benefit of basal insulin that has low day-to-day variability and therefore provides fasting glacaemia.”

In Diabetologia, Mark Rutter, of the division of diabetes, endocrinology, and gastroenterology at the School of Medical Sciences at the University of Manchester, pointed to some of the limitations of the DEVOTE trial. 

First, Dr Rutter noted that these data will have a useful impact on the way clinicians practice by bringing the subject of glucose variability to the attention of clinicians treating type 2 diabetes. 

“In individuals with type 2 diabetes, who are mostly managed in primary care, this association is not ‘on the radar’ for most clinicians,” he wrote. “The study should certainly make clinicians more aware of how glucose variability is associated with severe hypoglycemia and mortality.”

However, he noted that the study’s inability to determine a causal relationship between glucose variability and mortality is a major limitation warranting further study before changing prescribing and treatment practices.

“In view of the uncertainty surrounding the nature of causal relationships, it would seem premature to recommend targeting glucose variability to reduce the risk of severe hypoglycemia or mortality,” Dr Rutter wrote. “Only the results of further clinical trials can genuinely guide physicians on whether to target glucose variability and risk for severe hypoglycemia to reduce the risks for cardiovascular disease events and mortality in these individuals.”

He also concluded that glucose variability should be a concern for clinicians, and lauded DEVOTE for bringing this issue to the forefront. 

“Preventing severe hypoglycemia in those with type 2 diabetes should already be a priority in clinical practice,” Dr Rutter wrote in the editorial.  “However, detection and prevention of hypoglycemia in type 2 diabetes is not given the attention that it deserves. Greater efforts should be made to identify individuals at high risk of
hypoglycemia.”

—David Costill