OBJECTIVE The purpose of this study was to determine if the International Hypoglycemia Study Group (IHSG) level 2 low glucose definition could identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials.
RESEARCH DESIGN AND METHODS A post hoc analysis of the SWITCH (SWITCH 1: n = 501, type 1 diabetes; SWITCH 2: n = 721, type 2 diabetes) and the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE; n = 7,637, type 2 diabetes) using the IHSG low glucose definitions. Patients in all trials were randomized to either insulin degludec or insulin glargine 100 units/mL. In the main analysis, the following definitions were compared: 1) American Diabetes Association (ADA) 2005 (plasma glucose [PG] confirmed ≤3.9 mmol/L with symptoms); and 2) IHSG level 2 (glucose confirmed <3.0 mmol/L).
RESULTS In SWITCH 2, the estimated rate ratios of hypoglycemic events indicated increasing differences between treatments with decreasing PG levels until 3.0 mmol/L, following which no additional treatment differences were observed. In SWITCH 2, the IHSG level 2 definition produced a rate ratio that was lower than the ADA 2005 definition. Similar results were observed for the SWITCH 1 trial.
CONCLUSIONS The IHSG level 2 definition was validated in a series of clinical trials, demonstrating its ability to discriminate between basal insulins. This definition is therefore recommended to be uniformly adopted by regulatory bodies and used in future clinical trials.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)