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COVID-19 Resource Center

Perspective from Daniel J. Drucker, MD
Disclosures: The authors report no relevant financial disclosures.
June 03, 2020
3 min read
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Long-term data lacking for hydroxychloroquine use in type 2 diabetes, COVID-19

Perspective from Daniel J. Drucker, MD
Disclosures: The authors report no relevant financial disclosures.
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Evidence suggests hydroxychloroquine may play a role in glucose homeostasis among select individuals with type 2 diabetes; however, data on long-term safety and efficacy are lacking, particularly in the setting of COVID-19.

“Even though hydroxychloroquine displays antihyperglycemic properties, we cannot imply its use in type 2 diabetes to be safe and effective in general, especially due to the lack of robust data on long-term safety and efficacy in this population,” Marco Infante, MD, an endocrinologist in the division of endocrinology at CTO Andrea Alesini Hospital in Rome and a research scholar with the Diabetes Research Institute at the University of Miami Miller School of Medicine, told Healio. “This is particularly true if we take into account the remarkable interindividual heterogeneity existing between patients with diabetes in terms of clinical features and cardiometabolic risk profile.”

“Even though hydroxychloroquine displays antihyperglycemic properties, we cannot imply its use in type 2 diabetes to be safe and effective in general.”

Hints of promise

Although the mechanisms of action underlying the glucose-lowering properties of hydroxychloroquine are still not entirely clear, evidence suggests the antimalarial drug may exert multifaceted effects on glucose regulation, including improvement in insulin sensitivity, increase in insulin secretion, reduction of hepatic insulin clearance and reduction of systemic inflammation, Infante and colleagues wrote in a literature review published in the Journal of Diabetes.

Preliminary studies have shown safety and efficacy of hydroxychloroquine at doses ranging from 400 mg to 600 mg per day in individuals with type 2 diabetes for short durations. Several studies have also demonstrated reduced risk for developing diabetes among people with inflammatory rheumatic diseases, including rheumatoid arthritis and psoriasis. The type 1 diabetes TrialNet international network is currently investigating the potential ability of hydroxychloroquine to prevent or delay progression from normal glucose tolerance to symptomatic type 1 diabetes among people with islet autoimmunity. In 2014, hydroxychloroquine was approved in India as a third-line, add-on agent for individuals with uncontrolled type 2 diabetes, the researchers noted.

However, as off-label use of hydroxychloroquine has increased during the COVID-19 pandemic, caution is warranted, according to the researchers.

“Even though hydroxychloroquine is considered as one of the safest disease-modifying antirheumatic drugs and has been widely used for the treatment of rheumatoid arthritis and systemic lupus erythematosus, data on long-term safety and efficacy of hydroxychloroquine in diabetes are still lacking,” the researchers wrote. “Therefore, the use of hydroxychloroquine in patients with diabetes should be carefully evaluated, particularly in subjects with established microvascular and/or macrovascular complications.”

Potential risks

Initiating hydroxychloroquine treatment in people with diabetes with preexisting microvascular or macrovascular complications may be hazardous due to possible drug-related toxicity, Infante said.

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Risk factors for potentially lethal cardiac arrhythmias induced by hydroxychloroquine include coexisting cardiomyopathy, left ventricular dysfunction, ventricular hypertrophy, coronary artery disease, heart failure, prolonged QT interval, and ventricular arrhythmia or unexplained syncope.

Chronic kidney disease can lead to reduced hydroxychloroquine clearance, increased drug bioavailability and subsequent risk for hydroxychloroquine-related adverse effects. Those with preexisting retinopathy or a history of macular edema should also avoid hydroxychloroquine, the researchers wrote.

“On the other hand, there is a long-standing experience with hydroxychloroquine use for the treatment of various inflammatory rheumatic diseases, and hydroxychloroquine has been proven safe and effective when used at appropriate doses for the treatment of such diseases,” Infante said. “In addition, among individuals affected by inflammatory rheumatic diseases, there are certainly large subsets of diabetic patients who use hydroxychloroquine as a disease-modifying antirheumatic drug. This suggests that the use of hydroxychloroquine in select individuals under certain clinical scenarios does not pose serious health risks and may even be associated with improved clinical outcomes, including glucose control.”

Research needed

Infante said large trials are needed to establish the long-term safety and efficacy of hydroxychloroquine in the setting of type 2 diabetes and COVID-19.

“Emerging evidence coming from observational studies suggests that the use of this drug for treatment of COVID-19 is not associated with benefit in hospitalized patients and may even be tied to an increased risk for QT interval prolongation and potentially lethal ventricular arrhythmias,” Infante said. “Therefore, there is an urgent need for randomized controlled trials aimed to address whether the risks of hydroxychloroquine outweigh the benefits, or vice versa, among different subsets of individuals and in the two distinct settings of prophylaxis and treatment of COVID-19.”

For more information:

Marco Infante, MD, can be reached at the Department of Systems Medicine, University of Rome Tor Vergata, Via San Nemesio 21, 00145, Rome; email: marco.infante@uniroma2.it; Twitter: @MarcoInfante_MD.