Clinicians should be aware of the potential for certain drugs to induce diabetes, especially in high-risk patients, according to a review recently published in Diabetologia.

Though several drugs have been found to interfere with glucose homeostasis, the study authors focused their review on 4 pharmacologic classes: glucocorticoids, antiretroviral therapies (ART), newer atypical antipsychotics, and immune checkpoint inhibitors.

With glucocorticoids, the daily dose and duration of treatment were reported to play a role in diabetes risk. Worsening glucose control was found to occur rapidly after glucocorticoid initiation in patients with diabetes, while for those without, the time to hyperglycemia onset varied.

Treatment with atypical antipsychotics was associated with both weight gain and rapid increase in blood glucose. Among these agents, clozapine and olanzapine were considered to impart the greatest risk for diabetes, while aripiprazole and ziprasidone had the lowest risk. 

As for ART, first generation nucleoside analogue reverse transcriptase inhibitors (eg, stavudine, zidovudine) and protease inhibitors were linked to both increased lipotoxicity and insulin resistance. Newer agents were found to have reduced toxicity.

Certain immune checkpoint inhibitors may also trigger diabetes. Compared with anti-CTLA-4 agents (eg, ipilimumab), the risk of diabetes was found to be higher with anti-PD1 (eg, pembrolizumab, nivolumab) and anti-PD-L1 (eg, atezolizumab, avelumab, durvalumab) therapies.

Despite potentially causing new-onset or worsening of diabetes, the authors noted that the benefits of these medications significantly outweigh the risks associated with their discontinuation.

“Nevertheless, clinicians should be mindful of the risk of deterioration of glucose homeostasis, especially in individuals with pre-existing risk factors, so that alternative therapies with a lower risk of hyperglycemia may be chosen whenever possible,” they stated.

For high-risk patients who are receiving medications known to alter glucose tolerance, careful monitoring is recommended. Lifestyle modification is considered a key step in both prevention and treatment of drug-induced diabetes. Metformin is recommended as a first-line pharmacotherapy when lifestyle changes are insufficient.

For patients with severe hyperglycemia or in those who experience diabetic ketoacidosis, insulin therapy is recommended and should be modified based on blood glucose monitoring results.       

“Newer glucose-lowering agents that may promote weight loss are of potential interest in the treatment of individuals whose diabetes occurs in a context of weight gain and insulin resistance,” the authors added.

Reference

Fève B, Scheen AJ. When therapeutic drugs lead to diabetes. Diabetologia. Published online March 4, 2022. https://doi.org/10.1007/s00125-022-05666-w