Drug-Induced Hypoglycaemia

Abstract

Drugs are the most frequent cause of hypoglycaemia in adults. Although hypoglycaemia is a well known adverse effect of antidiabetic agents, it may occasionally develop in the course of treatment with drugs used in everyday clinical practice, including NSAIDs, analgesics, antibacterials, antimalarials, antiarrhythmics, antidepressants and other miscellaneous agents. They induce hypoglycaemia by stimulating insulin release, reducing insulin clearance or interfering with glucose metabolism. Several drugs may also potentiate the hypoglycaemic effect of antidiabetic agents. Administration of these agents to individuals with diabetes mellitus is of most concern. Many of these drugs, and depending on clinical setting, may also induce hyperglycaemia. Drug-induced hepatotoxicity and nephrotoxicity may lead in certain circumstances to hypoglycaemia. Some drugs may also induce hypoglycaemia by causing pancreatitis. Drug-induced hypoglycaemia is usually mild but may be severe. Effective clinical management can be handled through awareness of this drug-induced adverse effect on blood glucose levels. Herein, we review pertinent clinical information on the incidence of drug-induced hypoglycaemia and discuss the underlying pathophysiological mechanisms, and prevention and management.

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

“…Insulin and insulin secretagogues (sulfonylureas) should be used with caution. 164,165 Growth hormone treatment should also be avoided because it can result in the development or an increase in the size or number of liver adenomas, along with severe hyperlipidemia. The use of growth hormone should clearly be limited to only those who are proven to have a growth hormone deficiency and, in this situation, close monitoring for liver adenomas and metabolic disturbances is critical.…”

Diagnosis and Treatment of Insulinomas in the Adults

“…Other medications are known to be liable to induce hypoglycaemia, mostly in aged patients and patients with associated diseases, or combination of treatments, or renal failure. Miscellaneous mechanisms may be involved: increased insulin release, reduced insulin clearance, interference with glucose metabolism, liver or renal toxicity (Ben Salem et al 2011). A list of the most commonly employed medications liable to induce hypoglycaemia has been given in the 2009 consensus (Cryer et al 2009): some of them are associated with a risk of hypoglycaemia with moderate quality of evidence: cibenzoline, gatifloxacin, pentamidine, quinine, indomethacin.…”

“…Salicylates in large doses (4-6 g/day) may produce rarely hypoglycaemia in adults, and more often in children, by reducing basal glucose production and possibly increasing sensitivity to insulin (Cryer 2008). Disopyramide (Marks & Teale 1999), non-steroid anti-inflammatory drugs, analgesics, antidepressants (Ben Salem et al 2011) and antifungal agents (Lionakis et al 2008) have been reported to induce hypoglycaemia. However hypoglycaemia appears to be rare with such medications, unless employed in combination with other medications or in patients with underlying diseases.…”

Aetiology of Spontaneous Hypoglycaemia in a South African Hospital

“…Post prandial hypoglycaemia typically occurs within 1-3 hours of meal ingestion as a result of rapid intestinal transport of glucose (16). Drug induced causes of hypoglycaemia include deliberate or accidental administration of insulin or insulin secretatogues such as sulphonylureas and meglitinides, quinolones such as gatifloxacin and clinafloxacin, quinine, pentamidine, betablockers, angiotensin converting enzyme inhibitors and venlafaxine (17)(18)(19)(20). The mechanisms of drug induced hypoglycaemia range from increased stimulation of insulin secretion, decreased clearance of insulin and interference of glucose metabolism (17).…”

“…Drug induced causes of hypoglycaemia include deliberate or accidental administration of insulin or insulin secretatogues such as sulphonylureas and meglitinides, quinolones such as gatifloxacin and clinafloxacin, quinine, pentamidine, betablockers, angiotensin converting enzyme inhibitors and venlafaxine (17)(18)(19)(20). The mechanisms of drug induced hypoglycaemia range from increased stimulation of insulin secretion, decreased clearance of insulin and interference of glucose metabolism (17). Endrocrinopathies that can cause or contribute to hypoglycaemia include hypoadrenalism, growth hormone deficiency and hypothyroidism (21)(22)(23).…”