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Image via MannKind Corp.

As the whole world is combating an unprecedented outbreak of the viral respiratory disease COVID-19, you may be wondering if it’s safe to continue taking inhalable insulin. Could it compromise your lungs? Or be rendered ineffective if you become sick?

People may be concerned because research shows that respiratory infections are more severe in those with diabetes.

We queried some of the country’s top experts and learned a lot in the process.

The short answer is that there’s no reason not to use inhalable insulin unless you are ill to the point of experiencing “acute respiratory distress” that requires hospitalization.

But there’s a lot more to know on this topic as well — including what weakens your lungs most, information on the newest inhalable insulin product under development, and how inhalable medications might be key to fighting the COVID-19 outbreak.

There is currently only one brand of inhalable insulin on the market, Afrezza, from Southern California-based MannKind Corp. The drug has been shown to be extremely effective, and quite safe in both clinical trials and real-world use since its launch in 2015.

We asked Mike Castagna, CEO of MannKind, about the interplay of colds and flu with using the Afrezza inhaler. “We don’t have any evidence that there’s an issue with absorption, and there’s no evidence that it exacerbates respiratory issues. The powder is not sitting in the lungs, but rather goes through the lungs like oxygen,” he says.

Official word from the company is: “In clinical studies, absorption of Afrezza was not impacted by upper respiratory infection (which typically includes scratchy or sore throat, sneezing, cough and runny nose).”

While Afrezza users often experience a cough at the outset of use, Castagna says they regularly work through colds and flu without issues. Some Afrezza users who experience a lot of mucus, or an extreme cough, may opt to switch to injectable insulin during the worst part of their illness, but “that’s up to you and your doctor. We don’t see absorption issues in Afrezza in upper respiratory infections,” he says.

While the predictions for COVID-19 spread are scary — up to half the U.S. population may get the viral disease — thankfully the huge majority of those cases are expected to clear up after relatively mild symptoms, including runny nose, headache, fever, and diarrhea. Experts confirm that people with diabetes are no more or less likely to contract the illness. But if they do get sick, the consequences can be more severe and special care needs to be taken to keep glucose levels under control.

“I don’t want to minimize the concerns people with diabetes may have. If you have good (glucose) control, most people will be fine. If you don’t have good control, that’s when we worry,” says Castagna.

He reminds us that we all need additional insulin when we’re sick, due to the stress on the body. But generally, he says, “We don’t recommend any changes to people’s insulin management due to coronavirus — unless you are in respiratory distress. Then you should contact your doctor and get into a clinic as soon as possible.”

John Patton, one of the nation’s premier experts in inhalable medication science, is a veteran of the team that developed the world’s first inhalable insulin, Exubera, from Pfizer. He is a co-founder and now board member of Aerami, a start-up developing a new formulation of inhaled insulin (details below).

“That’s actually the most common safety question on inhaled insulin — what happens when you get cold or flu?” Patton tells DiabetesMine. “Pfizer actually ran trials where they gave people rhinovirus to do testing. We did not find that episodic lung diseases or infections were cause for concern.”

Once that first inhalable insulin product was out on the market, “all kinds of people got the flu and there was never a serious adverse event associated with having the flu. Of course, we don’t know how many people reverted to injections when they were sick,” he says.

(Note that Exubera was pulled from the market in 2007, for business reasons having nothing to do with negative health outcomes.)

Patton makes a point of noting that when sick, you need to manage blood glucose carefully, to avoid going into diabetic ketoacidosis (DKA). See NIH diabetes sick day guidelines here.

Whose lungs are at highest risk?

The people who appear to be at “enormous risk” of developing worst-case-scenario COVID-19 are smokers, whose lungs are filled with high loads of tar, Patton says.

Vaping is also suspected to make COVID-19 cases worse, although there is no solid data on this yet.

A gender gap is also emerging, where more men are being infected and dying of COVID-19 than women. One theory is that this is tied to significantly higher rates of smoking among men than women across the world. But the LA Times reports that other factors may be at play, such as a theory that the hormone estrogen may have “specific protective powers” against this virus.

MannKind is also not expecting any product shortages due to the outbreak, despite the fact that they manufacture the product in Connecticut, which is currently 12th on the list of hardest hit states.

“We have months of inventory on hand. We’re making another batch as we speak,” Castagna tells DiabetesMine. “We’re taking measures to secure safety, of workers and the product, at our factories.”

A company alert issued on March 25 reminds patients and doctors that “pharmacies can order additional supplies from wholesalers with expected delivery within 1-2 days, as usual.” They also note that patients can receive Afrezza by mail-order, and that many insurance companies are allowing 90-day refills during this time.

The company has had difficulty gaining traction with Afrezza, because so many doctors and patients still just don’t know it’s an option, Castagna says. They currently have a user base of 6,000 to 7,000 individuals, half with type 1 diabetes and half with type 2. They don’t have specific stats on age groups, but do know that 20 percent of their users are on Medicare, so presumed older; and 80 percent are on Medicaid or private insurance, which implies younger users.

Although they started out targeting type 2s, they’re now shifting almost 100 percent of their energy towards the type 1 market, a decision that was made in January 2020. Castagna points out that they now have 20 to 30 people on staff who live with type 1 diabetes themselves.

Basically, they want to prioritize their resources where they can have the most impact, he says. And people with type 1 are most keenly tuned in to achieving better time-in-range, fewer hypoglycemic episodes, and less sleep disruption. Data presented at the February 2020 ATTD international diabetes technology conference showed a 1.6 percent reduction in A1C and significant reduction of hypos using Afrezza versus injected insulins.

Castagna says they’re seeing increased demand for the product every week, “and we don’t anticipate any slowdown, other than the fact that people won’t be seeing their doctors in the coming weeks, so that will slow down prescriptions overall.”

They’re apparently achieving 70 percent approval on prior authorizations “within hours,” he says, as their CoverMyMeds program has been quite effective.

As far as COVID-19 concerns go, Castagna adds: ”We’ve had zero calls as of last week from HCPs (healthcare providers) on this issue. But our reps are equipped to answer questions.”

“We don’t want people running around scared, saying, ‘I’ve got to get off my Afrezza.’ We don’t see any indication for that… A large majority of people will get COVID-19 but a large majority will not have symptoms strong enough to warrant a change in their insulin.”

If you use Afrezza and have questions, you can contact their Customer Service at 818-661-5047 or guide@mannkindcorp.com.

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Image via Aerami Therapuetics

We also connected with North Carolina-based Aerami Therapuetics (formerly Dance Pharmaceuticals), which is working on a next-generation inhalable insulin product.

Theirs is a fine mist aerosol formulation instead of a powder, delivered by their new inhaler device called AFINA. It will have built-in Bluetooth capability to track data and integrate with apps and platforms. The company has completed seven early stage trials to date, and is now looking for a partner for their phase 3 study design with the Food and Drug Administration.

They are also working on an inhalable GLP-1 drug, which would be the first needle-free option for that type 2 diabetes drug.

About the new coronavirus, Aerami COO Timm Crowder says: “We’re seeing acute respiratory issues now with this virus which are pretty unique. It’s probably not something people have put a lot of thought into. Is this the new normal…?”

But he says their inhalable drug formulation should be perfectly safe and effective for those with “normal” cold and flu symptoms — perhaps even more so than Afrezza.

“Ours is a soft liquid, that’s shown no cough, and been very gentle on the lungs in trials. Our high peripheral deposition (HPD) insulin droplets go into the deepest part of the lungs. Even with congestion, you’re not typically going to see mucus in that part of the lung,” Crowder explains.

The AFINA inhaler is a small black square device outfitted with a light that blinks to alert the user as to how effective their inhalation technique is. It comes with a small dropper vial full of insulin mist, that has to be used to fill the inhaler before each mealtime (bolus-only) dose.

The big differentiators for this product are its precise delivery, those small droplets that go into the deep lungs, and “breath actuation,” meaning the ability to let users know how well they are absorbing the product, Crowder says.

“With our device, the aerosol droplets are only generated when the inhalation is in target range, shown by the flow sensor on the device — in other words, only when the patient inhales properly. If they’re not inhaling appropriately, the device will glow yellow, showing that no dose is being delivered. They either need to slow down or speed up their inhalation technique.”

“Also, our dosing is extremely targeted. We can control precisely where the droplets go,” he adds.

They’re not yet providing a projected launch date, and are still determining basics like whether a spirometry lung capacity test will be required to get prescription for this inhaler (as is the case with Afrezza), or whether they will mainly target type 1 or type 2 diabetes. Human clinical trials will determine all that, Crowder says.

Despite the current worldwide respiratory virus crisis, the overall promise of inhalable medications to effectively treat conditions free of needles is huge, Crowder says.

It’s important to note that on March 17, Afrezza maker MannKind announced that the company will be shifting its pipeline to also work on three potential COVID-19 treatments with development partners. These aim to reduce replication of the virus in the lungs, and delay the “inflammation cascade” that leads to acute respiratory distress syndrome. These will be in the form of dry powder inhalers that deliver the medication directly into the lungs.

Expert Patton, who is now also co-founder of iPharma, an “International Inhalation Center of Excellence” that helps develop and test new medical inhalation products, tells us that with the current COVID-19 pandemic, “people with ideas for therapies are coming out of the woodwork.”

Patton points to a paper just published by the University of California, San Francisco and international scientists listing 72 molecules that could have an impact on treating the novel coronavirus. (Among the substances listed is the diabetes drug metformin, we noticed.) Patton lauds this as “remarkable work” but cautions that this may lead to a potentially dangerous explosion of off-label use of these molecules: “People aren’t going to wait for clinical trials.”

Case in point: Just a few days ago, a man died in Arizona after self-medicating with what he thought was an experimental substance that could combat the new coronavirus that causes COVID-19.

Patton also notes that most of the ideas for new COVID-19 therapies are oral or injection prototypes, which could have toxic properties. “Ideally, they should be inhaled,” he says.

“Local lung delivery has always had very strong potential. It offers targeted delivery, that can lower overall dose and raise the effect on the cells you want to target.”

A classic example is newer inhaled steroids used for asthma or COPD, he says. Oral or injected steroids can be quite toxic, especially in children. “They’re essentially going through the whole body. But with inhaled medications, you get targeted treatment, that only impacts the affected cells. It’s like with some drugs that can kill cancer, but they will also kill you,” Patton explains.

The benefits of inhaled steroids are enabling a high concentration of the drugs to reach only the impacted areas of the body, reducing adverse side effects and allowing for smaller, more effective dosing.

Patton is not alone in believing that inhalation devices can have a huge impact on improving healthcare.

But of course with the cautionary note: “If you have irritated lungs or lungs that are sensitive, there’s just a physical irritation that happens with anything — even good things that are not toxic, like mother’s milk.”

The bottom line, according to Patton, is: “If you are really sick and coughing, you may not want to inhale anything.” But if your lungs are otherwise healthy, there’s no inherent danger in it.