Careful consideration of the risks and benefits of treatment should be taken before the use of hydroxychloroquine in patients with diabetes, particularly within the setting of the novel coronavirus disease 2019 (COVID-19) pandemic, according to a review published in the Journal of Diabetes.1
There are currently no drugs approved for the treatment of COVID-19. As a result, many drugs are being repurposed for off-label use against COVID-19 in hospital settings, including chloroquine and hydroxychloroquine. While robust clinical trials of these drugs remain to be performed in patients with COVID-19, professional societies urge that clinicians take into account risks associated with hydroxychloroquine use in certain populations, including patients with diabetes.
A growing body of evidence suggests that hydroxychloroquine may play a role in the regulation of glucose homeostasis in patients with and without diabetes. Preliminary clinical trials in patients with type 2 diabetes have repeatedly demonstrated that use of hydroxychloroquine is associated with improved glycemic control and significant reductions in glycated hemoglobin (HbA1c) levels.
Although the mechanisms of this activity are not entirely clear yet, it has been suggested that hydroxychloroquine improves insulin sensitivity, increases insulin secretion, and reduces systematic inflammation. Mechanistic studies have been performed in animals and humans alike and suggest that the antihyperglycemic activity is multifaceted.
Collectively, studies indicate that chloroquine and hydroxychloroquine use are associated with lower glucose levels as well as higher insulin levels due to increased rates of secretion and inhibition of degradation. It has been suggested that hydroxychloroquine may increase insulin sensitivity and improve beta-cell function, although this activity has been contested. A randomized study (ClinicalTrials.gov Identifier: NCT02026232) has been undertaken to evaluate the effects of hydroxychloroquine on insulin sensitivity and metabolism in patients with type 2 diabetes.
The anti-inflammatory properties of hydroxychloroquine have been demonstrated in a variety of inflammatory rheumatic diseases, including rheumatoid arthritis and systemic lupus erythematosus. The immunomodulatory effects in the context of type 2 diabetes are less clear, though hydroxychloroquine use is associated with improvements in lipid levels. Less data are available regarding the use of hydroxychloroquine in type 1 diabetes, but a clinical trial has been designed to investigate the effects of the drug to prevent or delay glucose intolerance or type 1 diabetes (ClinicalTrials.gov Identifier: NCT03428945).
Although hydroxychloroquine is considered a safe treatment option for patients with rheumatic diseases, the long-term safety of hydroxychloroquine use in patients with diabetes is unclear and the drug is not without side effects. Use of hydroxychloroquine, particular at high doses or for long durations, is associated with retinal toxicity and cardiotoxic effects, including potentially lethal heart rhythm disorders. The risk for cardiac arrythmias is most pronounced in patients with underlying cardiac conditions or in those using drugs that prolong QT intervals, such as azithromycin, antivirals, and antihistamines.
Chronic kidney disease may also reduce the clearance of hydroxychloroquine and may contribute to increased risk for adverse effects.
The review authors emphasized that a proper risk-benefit assessment be performed before utilizing hydroxychloroquine in patients with diabetes within the backdrop of COVID-19. Although accumulating evidence suggests that hydroxychloroquine may have useful antidiabetic properties, observational studies thus far suggest that the drug is not associated with improvement in COVID-19 symptoms or duration and the Food and Drug Administration currently cautions against off-label use of hydroxychloroquine for treatment of COVID-19.2
In addition, emerging evidence suggests that diabetes represents an important risk factor for disease severity and prognosis in patients with COVID-19. With consideration to the interplay between diabetes and COVID-19, the review authors concluded that “a pre-emptive and careful evaluation of all the potential risks and benefits related to [hydroxychloroquine] is critical for a proper and cautious use of this drug in subjects with diabetes, particularly in the context of COVID-19.”
1. Infante M, Ricordi C, Fabbri A. Antihyperglycemic properties of hydroxychloroquine in patients with diabetes: risks and benefits at the time of COVID-19 pandemic [published online May 13, 2020]. J Diabetes. doi:10.1111/1753-0407.13053
2. US Food and Drug Administration. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. April 24, 2020. Accessed May 20, 2020.