Drugs and diabetes

A wide variety of frequently prescribed medications are known to cause glucose intolerance and/or to precipitate overt diabetes mellitus in nondiabetic individuals or to worsen glycemic control in subjects with established diabetes mellitus. These adverse effects on glucose homeostasis are exerted both by the induction of insulin resistance and by the inhibition of insulin secretion. Because diabetic patients have other associated medical problems, they commonly are treated with a variety of drugs that have the potential to cause a worsening of glucose tolerance. Elderly subjects represent another group with diverse medical problems that require multiple drug therapies. Because glucose intolerance is a characteristic feature of the normal aging process, the development of impaired glucose tolerance or even frank diabetes mellitus is frequently observed when older patients are treated for these underlying medical disorders. Antihypertensive drugs, including the diuretics and the β-adrenergic blockers, have long been known to cause a deterioration in glucose tolerance. All cases of diuretics (thiazides, loop diuretics, potassium-sparing diuretics) and both the specific and nonspecific β-blockers have been associated with glucose intolerance. The α-agonists (clonidine) also have been shown to worsen glucose tolerance. Nicotinic acid, a commonly employed antilipidemic drug, causes severe insulin resistance and may precipitate frank diabetes mellitus. Numerous other drugs including immunosuppressant agents (cyclosporin and glucocorticoids), antibiotics (pentamidine, isoniazide), anticonvulsants (Dilantin), β-adrenergic agonists, ethanol, phenothiazines, lithium, aspirin, and others also have been shown to impair glucose tolerance. Where information is available, the mechanism(s) via which these drugs impair glucose homeostasis are discussed. It is anticipated that a careful reading of this review will alert the clinician to the large number of diverse medications that have the potential to cause glucose intolerance in nondiabetic individuals and to interfere with the achievement of normal glycemic control in diabetic patients.