Everything You Need to Know (and More) About Afrezza Inhaled Insulin
by Gary Scheiner MS, CDCES
One of my favorite rules of diabetes management is “If it ain’t broke, don’t fix it”. This adage has gotten me out of plenty of household chores and some challenging appointments with clients who were seeking absolute perfection with their diabetes management. But I have to admit, “ain’t broke” is a relative term. Who’s to say what is truly “not broken”? After all, if things can be made better or easier, why not give it a try?
For the past five+ years, I’ve been very satisfied with the open-source (DIY) Loop hybrid closed loop system. I find it flexible and easy to use. It also produces nice-enough glucose levels and makes diabetes pretty easy to live with. But for the good of science, I’m always willing to try an alternative.
Recently, a research study called “INHALE-3” was presented at the American Diabetes Association’s Scientific Sessions. It showed similar A1c and time-in-range between users of AID (automated insulin delivery) systems and regimens that utilize injected long-acting insulin and Afrezza as the bolus insulin.
Afrezza, developed and marketed by MannKind Corporation, features recombinant human insulin in dry powder form (called Technosphere) and a whistle-like device for inhaling it. It is approved for adults only and is not to be used by smokers or people with chronic lung disease.
Once in the lungs, Afrezza absorbs quickly into the bloodstream. By avoiding the need to absorb through the fat layer below the skin, Afrezza starts working within a couple of minutes, peaks in about 30 minutes, and clears in about 90 minutes (the duration is slightly longer at larger doses). This is more than twice as fast as traditional “rapid-acting” insulin (aspart, lispro and glulisine), which takes nearly 15 minutes to start working, peaks in 60-90 minutes, and lasts a full 3-5 hours. The new “ultra-rapid” insulins (Fiasp and Lyumjev) are only a few minutes faster than rapid insulin.
Anyone who has heard me speak knows that I like to put the term “rapid acting insulin” in quotes (like I just did here) because it’s a lie. Rapid insulin is only more rapid than “regular” insulin. It comes nowhere close to matching the speed of insulin produced by the pancreas.
I knew from prior experience that Afrezza works much faster than rapid insulin, so I decided to use it as my exclusive bolus insulin for two weeks. It was a tremendous learning experience.
Here’s what I discovered.
The Basal Behind the Bolus
Let’s get this out of the way first. Nobody with T1D can get away with using just Afrezza. A basal insulin is also required.
Over the two week period, I tried a few different approaches to basal insulin just to see if one worked better than the others. And I found that it does matter. When using injected basal insulin (in the form of Tresiba/degludec), I found that my glucose levels were very unstable – especially during the times when my basal is normally at its highest and lowest. I was constantly rising in the early part of the night and dropping in the afternoon.
So I went back to using my pump system for basal delivery only, and entered my carbs and Afrezza doses manually into the Loop app.
Applying Afrezza
The Afrezza bolus process is fairly simple.
Load a cartridge (the size of a little greenhouse from Monopoly) into the whistle-like inhaler, put the mouthpiece in your mouth and inhale slowly.
It took a few days to become comfortable with the inhalation process. At the beginning, I would cough right after every inhalation. Sometimes, a cloud of “insulin smoke” would come out of my mouth, which made me worry that I did not receive the full dose. It also made me worry that people around me could breathe in “second hand” insulin. But now I have the procedure down pretty good. A sip of water beforehand and inhaling with a little less force works really well.
The insulin cartridges come labeled as 4, 8 and 12 units.
I say labeled, because they don’t actually work like 4, 8 and 12 units of the insulin we’re used to using. They work more like 2.5, 5.0 and 7.5 units, respectively. If you need more than 7.5 units, you can load another cartridge and do a second inhalation right after the first.
Figuring out the right doses takes some trial and adjustment. I started out with the lowest (2.5u) cartridges and increased from there – using a small/medium/high-carb meal approach. For correcting high glucose values, I only used the low (2.5u) cartridges, as this is enough to lower me about 150 mg/dl based on my sensitivity to insulin.
Dosing in increments of less than 2.5 units requires the “Tony Montana” approach, based on Al Pacino’s character in the movie Scarface.
One must separate the tiny insulin-containing chamber from the rest of the cartridge, tap the powder onto a clean surface, split it into two halves with a credit card, scoop one of the halves back into the chamber, and snap it back into the rest of the cartridge… all without coughing or sneezing it all into oblivion. It works, but it is very inexact, tedious, and completely off-label.
Because of its rapid peak and clearance, the timing of Afrezza also required some adjustments. After nearly 40 years of being told, “Take your insulin before you eat!”, I learned that you can’t do that with Afrezza. Doing so will usually cause a low shortly after (or during) the meal.
In fact, most meals consisting of low-to-medium glycemic-index foods require a modest dose with the meal and a second dose two hours later. This is due to the extended digestion that takes place. Very few meals are finished digesting in 90 minutes; any digestion that takes place after 90 minutes will cause a delayed rise unless a second dose of Afrezza is given.
Top-Line Results
Bear in mind that this is an “N” of 1: It is inappropriate to draw firm conclusions from a very small sample size. Nevertheless, my overall glucose control was worse when using Afrezza compared to my usual AID system. My customary time-in-range of 75-80% went down to about 65%, and my average went from 141 to 157 mg/dl. There was no significant change in the frequency/duration of hypoglycemia, although my lows were more severe with Afrezza – mostly from trying to correct highs with a dose that was more than I likely needed.
One area that improved was my post-meal glucose.
I usually have cereal in the morning, and it was nice to not spike up to 200+ mg/dl soon after eating. I don’t usually spike that high after other meals and snacks, but even those were better with Afrezza. However, I did have to take a second dose of Afrezza after almost every lunch and dinner, unless the meal was very low in both fat and protein.
One other area of improvement with Afrezza was with post-meal exercise.
I often work out 1-2 hours after breakfast or dinner, so my glucose usually starts out a little on the high side and then drops significantly. With Afrezza, I went into the workouts with better control and did not drop nearly as much since the bolus was almost completely gone during the workout.
Here are what I see as some of the pros and cons associated with Afrezza use:
PROS
+ High readings can be brought down much faster than with rapid-acting insulin
+ Post-meal glucose peaks are minimized
+ No need to pre-bolus
+ Far less glucose decline when exercising 1-5 hours after bolusing
+ Insulin action is not affected by dehydration, site irritation or lipodystrophy.
+ No needles required for taking bolus insulin
CONS
One of the biggest issues with Afrezza is the inability to dose in increments of less than 2.5 units, unless you are willing to go “off label” and split the small cartridge dose like a coke-head (using the procedure described above). Otherwise, it can be difficult to fine-tune glucose levels. The dose increment is impractical for those who are even moderately sensitive to insulin. For many people, even 2.5 units is too much to correct modest hyperglycemia or cover small meals/snacks, forcing some to conform their food portions to match the insulin dose. This, to me, is a step backwards in the way we live with and manage diabetes.
The speed of Afrezza is a bit of a double-edged sword. While effective for limiting post-meal glucose spikes, it is important to remember that most food takes several hours to fully digest. Afrezza simply works too quickly for the average American meal and can produce post-meal lows unless the dose is delayed or split. With most meals, there is a need to monitor glucose levels 1-2 hours post-meal to see if/when a second dose is needed. A glucose rise 2-4 hours post-meal is common if second doses are not given. These extra thought processes add to the burden of an already burdensome disease.
Some other drawbacks:
– Basal insulin is still required (via injection or pump)
– Lung function testing required before prescribing and every 6-12 months thereafter
– Very slight (approx. 1%) decrease in lung function may occur (NO significant lung safety trends reported in 10+ years)
– Often requires preauthorization for insurance coverage
– Must carry inhaler and cartridges
– Inconvenient to administer insulin (compared to bolusing with a pump)
– Coughing is a common side effect
– Long-term effects on lung function are not entirely understood
– Large doses require multiple inhalations
– Inhaling in public carries a “vaping” stigma
Many of Afrezza’s drawbacks can be minimized by working with a healthcare team that understands the nuances of the product. A good CDCES (Certified Diabetes Care & Education Specialist) can be invaluable in helping Afrezza users learn proper inhalation technique, determine optimal doses, and optimize dosage timing.
Who can benefit most from Afrezza?
Based on the benefits and drawbacks associated with Afrezza, I believe that certain people are optimal candidates:
- Those with severe, untreatable needle phobia (keeping in mind that basal insulin will still need to be taken)
- Anyone with widespread lipodystrophy, for whom injected insulin is highly unpredictable
- People whose diets are similar day-to-day, consistently low in fat, and high in rapidly-digesting (high glycemic index) carbohydrates
- Those who prefer to exercise 2-4 hours post-meal and tend to experience hypoglycemia
- Those who struggle with excessive post-meal glucose spikes despite applying strategies to mitigate the rise (earlier bolusing, use of ultra-rapid insulin, consuming slower-digesting foods, post-meal physical activity, etc…).
Even if you don’t fall into one of these categories, it may still be worth having Afrezza available. These are some of the situations in which Afrezza may come in handy:
- Fixing very high glucose levels
- Bolusing for very-high-glycemic-index meals/snacks
- Covering meals when pre-bolusing is not possible
- Addressing hyperglycemia caused by a pump/infusion site malfunction, or any time dehydration is present (dehydration impairs insulin absorption below the skin)
- Covering meals or fixing hyperglycemia an hour or two prior to exercise
Interestingly, the INHALE-3 study found that overnight control was superior in people who used an AID system compared to Afrezza with injected basal insulin. But consider the possibility of combining the two regimens: automatically-adjusted basal insulin from a pump, bolusing with the pump for “typical” meals, and Afrezza to deal with the highs, super-fast-acting foods, and prior to workouts.
Our understanding of Afrezza grows each day. If you have any questions, feel free to reach out to me or anyone on the Integrated Diabetes Services clinical team. And if you have experience with Afrezza and would like to share any tips/tricks, please do so! We all do best when we work together.
