New Recommendation on Reporting Hypoglycemia in Clinical Trials

In the January 2017 issue of Diabetes Care, the International Hypoglycaemia Study Group published a recommendation that glucose levels lower than 3.0 mmol/L (54 mg/dL) be documented in clinical trials of glucose-lowering diabetes drugs.¹ The group consists of experts from numerous international and US institutions, including Washington University, the University of Virginia, and the University of Minnesota.

“Hypoglycemia is perhaps one of the most important barriers to glycemic control in patients with diabetes, as hypoglycemic episodes can not only limit the ability to obtain the glycemic target, but they may also result in harm to the patient,” Kevin M. Pantalone, DO, staff endocrinologist and director of clinical research at the Cleveland Clinic in Ohio, told Endocrinology Advisor. “It would thus be very important to recognize the frequency of hypoglycemia in a standardized manner when conducting clinical trials, particularly when evaluating the efficacy and safety of antidiabetic therapies.” 

The American Diabetes Association (ADA) previously defined hypoglycemia as any episode of abnormally low glucose that could result in harm to an individual.² It had not been defined numerically because glycemic “thresholds for responses to hypoglycemia vary, not only among individuals with diabetes but also in the same individual with diabetes as a function of their HbA1c levels and hypoglycemic experience,” wrote the authors of the new paper. During intensive glycemic treatment, for example, an increased frequency of iatrogenic hypoglycemia can cause the glycemic threshold for hypoglycemia and related glucose counterregulatory responses to shift to lower glucose concentrations.

Despite such variability, the study group emphasized the importance of identifying a specific glucose concentration indicative of a level of hypoglycemia that clearly presents the risk for harm and thus should be avoided.

“Increasingly in our discussions, our group felt that the diabetes community was failing to appreciate the potentially serious consequences of glucose levels, which were not considered ‘severe’—meaning needing the help of another person to recover—and which were not captured systematically in clinical studies,” co-author Simon Heller, MD, a professor of clinical diabetes at the University of Sheffield in the UK, said in an interview.

Additionally, the use of different classification systems by various groups such as pharmaceutical companies has led to difficulty in comparing treatments.

“We feel that if the diabetes community can agree on a glucose level that captures this information, we can both calculate the clinical risk to patients and more effectively compare treatment approaches that aim to reduce rates of hypoglycemia. This would be an important advance,” said Dr Heller.