Two cases are described where diabetic ketoacidosis was found in conjunction with significant levels of prescription drugs. Case 1: A 45-year-old woman with a history of insulin-dependent diabetes mellitus was found to have Armanni-Ebstein nephropathy characteristic of hyperglycaemia with a vitreous humour glucose level of 63.1 mmol/L and a beta-hydroxybutyrate level of 14.25 mmol/L. Ancillary toxicological evaluation revealed a lethal level of sertraline (2.5 mg/L), with an elevated level of methadone (0.23mg/L). Death was due to diabetic ketoacidosis complicating mixed drug toxicity. Case 2: A 27-year-old man with a history of insulin-dependent diabetes mellitus was found to have Armanni-Ebstein nephropathy with a vitreous humour glucose level of 51.7 mmol/L and a beta-hydroxybutyrate level of 18.6mmol/L. Ancillary toxicological evaluation revealed a potentially lethal level of methadone of 0.39mg/L. Death was attributed to diabetic ketoacidosis complicating methadone toxicity. These cases demonstrate a situation where drug toxicity led to diabetic ketoacidosis resulting in death most likely from a combination of factors. Measuring vitreous humour glucose and beta-hydroxybutyrate levels is important in individuals with histories, or scene evidence, of insulin-dependent diabetes mellitus, in addition to toxicological screening when there is evidence of possible drug taking. It appears that drug intoxication in both cases had impaired the ability to administer insulin, resulting in the development over time of diabetic ketoacidotic states. Lethal mechanisms were, therefore, more complex than simple drug toxicity or diabetic ketoacidosis in isolation.