What’s the Deal with Hydroxychloroquine and Diabetes?

HCQ is an oral tablet, available as a generic drug and under the brand name Plaquenil. It’s generally known as an antimalarial treatment, but is also used with rheumatoid arthritis to help relieve inflammation, swelling, stiffness, and joint pain. Researchers have also found that it helps with flare-ups of the autoimmune illness lupus.

HCQ is proven to have beneficial anti-inflammatory effects, but it falls into a class of drugs that prolong the “QT interval” in the heart. Simply put, this is the length of time between normal contractions of the heart as it beats. Prolonging this time can cause arrhythmias — dangerous heart rhythm disruptions that can cause cardiac arrest or death.

After scientists floated the idea of using antimalarial medications to treat COVID-19 (among many early concepts), Trump latched onto the notion that hydroxychloroquine will prevent people from contracting the deadly virus. He has been hyping it for months, even though the Food and Drug Administration (FDA) issued a clear warning against its use for COVID-19 on April 30.

The FDA warned of “serious heart-related adverse events and death in patients with COVID-19 receiving hydroxychloroquine and chloroquine, either alone or combined with… other QT prolonging medicines.”

On May 21, the New York Times’ Fact Check team reported, “The president falsely described scientific research around the malaria drug, falsely denied the existence of a federal warning against it and argued, with no evidence, that large numbers of health care workers were taking it.”

On top of that, the president recently claimed he’s taking the drug himself experimentally in a 2-week regimen. Experts and celebrities alike have decried this practice. TV host Jimmy Kimmel quipped: “None of this adds up. Trump said he’s going off hydroxychloroquine in 2 days when his ‘regimen’ runs out… that’s not how that drug is taken. It’s not an antibiotic. There’s no ‘regimen.’ It’s taken prophylactically, which means you have to keep taking it. Like condoms are prophylactics. You don’t use them for 2 weeks and then go, ‘I think we’re good, honey.’”

To date, there is no data to support the fact that HCQ effectively prevents or treats COVID-19 in the general population. Still, some believe it may be worth pursuing as a treatment for those at highest risk.

“If the question is, does hydroxychloroquine improve survival in adults with type 1 and type 2 diabetes infected with COVID-19, the answer is we do not have sufficient data to form a conclusion,” Stanford endocrinologist Dr. Rayhan Lal tells DiabetesMine.

He points to a meta-analysis paper (summary of high-quality studies) on hydroxychloroquine in diabetes published in February 2020, in which the authors summarize some “antidiabetic” effects of taking the drug seen in type 2 patients.

There were also some early in vitro and observational studies out of China and France, he says, but results are inconclusive to date. One study from the Department of Veterans Affairs published in April 2020 showed an overall increased mortality rate in COVID-19 patients treated with hydroxychloroquine alone. Other studies show little effect at all.

A large-scale multinational observational study of HCQ use for COVID-19 was just published in the respected journal Lancet. The researchers concluded, “we did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens… was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19.”

Lal sums it up this way: “At present the largest trials show no evidence of benefit and reveal some possibility of harm. But all that being said, if you really want to know the answer for adults with diabetes it would require a rigorous masked, randomized controlled trial to evaluate risks and benefits.”

Interestingly, outside of coronavirus concerns, research shows that hydroxychloroquine can improve glycemic control in people with type 2 diabetes.

A recent Journal of Diabetes Research article cites a study outside the United States showing that hydroxychloroquine, combined with another oral drug (atorvastatin), reduced T2 patients’ A1C significantly and even appeared to have an impact on reducing hypoglycemia (dangerous low blood sugar).

In fact, hydroxychloroquine has been approved as an “add-on” treatment for type 2 diabetes in India since 2014. That means it’s given to patients who don’t achieve glycemic targets with two other oral glucose-lowering drugs. But it’s not likely to be used this way in America any time soon.

“I doubt the drug would ever be approved for T2D in the U.S. due to what it does to QT prolongation,” says Dr. Irl Hirsch, clinician and researcher at the University of Washington Diabetes Institute. “Part of the problem is that in diabetes, we see more arrhythmias anyway due to CAD (coronary artery disease) so these drugs can be very dangerous.”

But he notes that the drug is not all bad, if used in low-risk populations for the right purpose where the benefits exceed the risks. “In fact, my wife has been taking it for a rheumatologic condition for 30 years now, and she has done fine with it. As a rule of thumb, I generally would not use this in someone with a high risk of heart disease, with or without diabetes,” Hirsch says.

A study published back in 2007 suggested that “among patients with rheumatoid arthritis, use of hydroxychloroquine is associated with a reduced risk of [type 2] diabetes.” But the data wasn’t conclusive because other factors may have been at play.

The researchers called for further evaluation of the potential role of hydroxychloroquine as a preventive agent for diabetes among high-risk individuals in the general population.

One additional small study in 2015 showed that HCQ can improve both beta cell function and insulin sensitivity in non-diabetic individuals, which “may explain why HCQ treatment is associated with a lower risk of type 2 diabetes.”

“But keep in mind that if hydroxychloroquine has anti-inflammatory effects, it can lower insulin resistance by simply reducing inflammation from the underlying disease,” explains Dr. Calvin Wu, an endocrinologist with Steady Health in San Francisco. He agrees that further research would be required to make any prevention claims.

Meanwhile, a first-of-its-kind nationwide study is exploring whether HCQ can delay or prevent early stage type 1 diabetes from progressing into the full-blown disease. The study is run by TrialNet, an international network of the world’s leading T1D researchers active at clinic sites around the world.

TrialNet claims that the drug is quite safe in this context, noting: “Hydroxychloroquine (HCQ) is approved by the Food and Drug Administration (FDA) and has been used for more than 60 years. It is used to treat other autoimmune diseases, including rheumatoid arthritis and lupus. HCQ has a good safety profile and is approved for use in children.”

The trial is still actively recruiting and not estimated to complete until August 2024. Details can be found here.

Hydroxychloroquine is a drug with proven benefits for treating malaria and certain autoimmune conditions. Despite the president’s claims, there is no evidence that it’s effective treating COVID-19 and may do more harm than good.

There is some evidence that HCQ can help keep type 2 diabetes in check, but the FDA has concerns about negative impact on heart health. It’s potential for halting the onset of T1D is just beginning to be studied.