Treatment of sulfonylurea and insulin overdose

Abstract

The most common toxicity associated with sulfonylureas and insulin is hypoglycaemia. The article reviews existing evidence to better guide hypoglycaemia management. Sulfonylureas and insulin have narrow therapeutic indices. Small doses can cause hypoglycaemia, which may be delayed and persistent. All children and adults with intentional overdoses need to be referred for medical assessment and treatment. Unintentional supratherapeutic ingestions can be initially managed at home but if symptomatic or if there is persistent hypoglycaemia require medical referral. Patients often require intensive care and prolonged observation periods. Blood glucose concentrations should be assessed frequently. Asymptomatic children with unintentional sulfonylurea ingestions should be observed for 12 h, except if this would lead to discharge at night when they should be kept until the morning. Prophylactic intravenous dextrose is not recommended. The goal of therapy is to restore and maintain euglycaemia for the duration of the drug's toxic effect. Enteral feeding is recommended in patients who are alert and able to tolerate oral intake. Once insulin or sulfonylurea-induced hypoglycaemia has developed, it should be initially treated with an intravenous dextrose bolus. Following this the mainstay of therapy for insulin-induced hypoglycaemia is intravenous dextrose infusion to maintain the blood glucose concentration between 5.5 and 11 mmol l -1 . After sulfonylurea-induced hypoglycaemia is initially corrected with intravenous dextrose, the main treatment is octreotide which is administered to prevent insulin secretion and maintain euglycaemia. The observation period varies depending on drug, product formulation and dose. A general guideline is to observe for 12 h after discontinuation of intravenous dextrose and, if applicable, octreotide.

Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2–4 and 10

“…SU compared to insulin glargine with background MET alone) across the four studies. This finding is consistent with established observations that SUs are associated with an increased risk of hypoglycaemia through excessive release of insulin, as a result of their mode of action as insulin secretagogues [25,26], and a higher rate of hypoglycaemia was also observed in patients receiving dulaglutide with MET ? SU, compared with other background therapies, in a pooled analysis of the AWARD phase 3 clinical trials [23].…”

Electrical Excitability of the Endoplasmic Reticulum Membrane Drives Electrical Bursting and the Pulsatile Secretion of Insulin in a Pancreatic Beta Cell Model

“…In this way, the treatment compensates the secretory defect in T2DM patients. An important problem with this approach is that the induction of insulin secretion takes place even at low levels of blood glucose and can cause severe hypoglycemia if not properly controlled (248).…”

Who gets antidotes? choosing the chosen few

“…Effects from excessive doses are fairly predictable. For example, excessive acetylcholinesterase inhibition (as seen following physostigmine for antimuscarinic toxicity) commonly results in cholinergic excess , excessive dextrose administration (for sulfonylurea toxicity) frequently leads to rebound hyperinsulinaemia and hypoglycaemia , and excessive doses of naloxone or flumazenil can precipitate withdrawal symptoms, agitated delirium and occasionally seizures, depending on the patient and toxin . The use of antidotes in mixed overdoses (which represent the majority of cases presenting to hospital) greatly increases the risks of adverse consequences.…”