OBJECTIVES: To examine the heterogeneity in the definitions of hypoglycaemia across Randomized Clinical Trials (RCTs) conducted with oral antidiabetic agents or insulin. METHODS: RCTs included in the Canadian Agency for Drugs and Technologies in Health (CADTH) reports for the second-line and third-line therapy for the patients with Type 2 Diabetes were examined. Definitions for overall, major, minor, severe, and nocturnal hypoglycaemia were extracted from 76 RCTs. The extracted definitions were compared to the definitions of the American Diabetes Association (ADA) and European Medicines Agency (EMA).   RESULTS: According to the ADA and the EMA, hypoglycaemia is defined as an event with a blood glucose (BG) ≤ 3.9mmol/L.  Only 4 out of 76 studies adhered to the ADA/EMDA definition of hypoglycaemia. Generally, hypoglycaemia was defined as a status with BG ranging from <4 mmol/L to ≤ 2.8mmol/L. Only 17 out of 33 RCTs that defined severe hypoglycaemia adhered to the ADA/ EMDA definition. Severe hypoglycaemia was defined as a symptomatic condition that required the assistance of a third person for resuscitative actions, with or without BG values spanning from <3.3 mmol/L to <2.0 mmol/L. Major hypoglycaemia was defined as patients being unable to treat themselves, with or without a BG value ranging from <3.1 mmol/L to ≤2.8 mmol/L.  Nocturnal hypoglycaemia was vaguely defined when reported, as episodes occurring after evening injection and before breakfast, or between bedtime and morning, or any 6 hours or longer interval between 11pm and 8am. CONCLUSIONS: Compared to the ADA and EMA proposed definitions of hypoglycaemia (BG≤3.9mmol/L), the studies included in our review had a substantial heterogeneity in their definitions of hypoglycaemia not only in terms of the BG values being used, but also with the inclusion of the symptoms. The heterogeneity in defining hypoglycaemia makes it difficult to compare the safety of interventions for their drug-induced hypoglycaemia.