Drugs and hyperglycemia: A practical guide

Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha). Abnormalities of the distal gluco-regulatory pathways of hyperglycemia involve decreased insulin secretion and frequent insulin resistance, whereas the proximal defects are unknown, thus limiting targeted treatment. Drug-induced diabetes is potentially reversible and the risk is underestimated. There is little information on its long-term effects on microvascular complications as clinical trials have not been long enough and neither have they focused on these factors. Overall management includes awareness of a drug's diabetogenic potential, underlying diabetes risk, benefits and risks of continuing vs discontinuing the drug, plus a consideration of drug duration and dose. While diabetes and its severity can be identified and controlled, the likelihood of future diabetes complications frequently cannot. This, balanced against the predicted benefit of the drug, results in clinical uncertainty. Empirical approaches to drug-related hyperglycemia include decreasing the dose or selecting an alternative treatment, if possible. In the absence of drug-specific evidence, treatment of drug-induced hyperglycemia and diabetes is similar to comprehensive standard diabetes care, including lifestyle modifications, oral/injectable antidiabetic agents and insulin. Important clinical considerations include surveillance of glucose before and during treatment and, in some cases, institution of diabetes preventive measures like lifestyle modification and early treatment. Future research is needed to elucidate pathophysiology and optimal targeted treatment for drug-induced diabetes and its long-term complications.