Background and Aims: Hypoglycemia is a major threat of insulin therapy, but only severe events are often considered as valid endpoints. Surrogates are required; mild events are logical candidates. The International Hypoglycemia Study Group (IHSG) proposed thresholds (3.9 and 3.0 mmol/L) for representative mild events, but evidence is scarce.
Materials and Methods: We studied the correlation of the rate (or the incidence) of non-severe events with the rate (or the incidence) of severe events in a study-level systematic analysis of published data (1/1/00-6/1/18) in insulin-treated patients. Mild event was defined as either “any hypoglycemia,” or “severe or confirmed <3.9 mmol/L,” or “severe or confirmed <3.0,” with a tolerance of +/-0.4 mmol/L to manage the multiplicity of definitions. Nocturnal period was defined as per study design, therefore not homogeneously. Severe events were mostly defined as per IHSG.
Results and Conclusion: 127 out of 15570 studies were eventually included. Pearson R² are presented (Figure). The mild hypoglycemia were usually better correlated with incidence rather than rate of severe events. Incidence of severe or confirmed <3.0 mmol/L, especially if limited to the night, appeared to be the best surrogate for incidence of severe events.
R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. A. Moutairou: None. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi. J. Gautier: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi.