Inhaled insulin offers an exciting opportunity for a faster acting insulin with fewer injections and lower chances of delayed hypoglycemia.
We all have them…mistakes we’ve made that we don’t even want to share with our own mother. Dr. Jeremy Pettus puts it all out there and gets real about what recently happened when he took the right dose of the wrong insulin.
by Juan Pablo Frias, MD
Achieving glucose goals is a critical part of overall diabetes management. The better the glucose control the lower the risk of long-term complications . Taking two or more glucose-lowering medications is usually needed in people with type 2 diabetes to achieve normal or near-normal glucose control.
This often means adding a long-acting basal insulin (for example, Lantus, Toujeo or Tresiba) to oral medication(s). Basal insulin primarily lowers fasting glucose and glucose levels before meals. If basal insulin and oral medications do not adequately lower overall glucose control, a commonly accepted next step in treatment is to add an injectable GLP-1 receptor agonist (RA) such as Byetta or Bydurion, Victoza, Trulicity, Tanzeum or Adlyxin. These medications primarily lower glucose values after meals and may also have effects on fasting glucose. Important to people with type 2 diabetes, the GLP-1 RAs often lead to weight loss. Treatment with a basal insulin and a GLP-1 RA makes a lot of sense since both fasting and post-meal glucose are addressed, helping to lower blood sugar levels further.
“Both new fixed-ratio combination products provide people with type 2 diabetes and their providers with a treatment option that is convenient, easy-to-use, and works to safely improve glucose control by combining two medications with different mechanisms of action in one pen device.” –Dr. Juan Frias
Until recently, people using basal insulin and a GLP-1 RA had to do so by administering each medication separately, therefore needing two separate injections. The FDA recently approved two products that combine basal insulin with a GLP-1 RA in one pen device. The two so-called “fixed ratio combination” products are Soliqua 100/33 and Xultophy 100/3.6. In published clinical trials, both combination medications were shown to result in better glucose control than basal insulin or a GLP-1 RA alone and with the added benefit of weight loss (rather than weight gain seen with insulin alone). Both medications did so without increasing the risk of hypoglycemia, and with fewer gastrointestinal side effects (e.g., nausea, vomiting, diarrhea) than with a GLP-1 RA alone. So, basically, these combinations offer better glucose control with lower risk of adverse effects than the individual components alone.
Soliqua 100/33 is approved for people with type 2 diabetes who are not achieving glucose goals on less than 60 units of basal insulin or lixisenatide. Xultophy 100/3.6 is approved for people with type 2 diabetes who are not achieving glucose goals on less than 50 units of basal insulin or liraglutide. Both Soliqua 100/33 and Xultophy 100/3.6 are administered once daily and come in a pen that is similar to an insulin pen. Like basal insulin, blood glucose levels should be monitored at least once daily in the morning (fasting) and the dose of the medication should be adjusted, if needed, based on fasting glucose values. The exact timing and amount of dose adjustment should be discussed with a healthcare provider. Precautions and contraindications should also be discussed with a healthcare provider, but in general, both medications have been shown to be very safe and well tolerated in appropriate people with type 2 diabetes.
Soliqua 100/33 is now available in the US and Sanofi, the manufacturer, provides a $0 co-pay card for qualifying commercially insured people as well as a COACH Program that provides support to people using the medication. Information on both programs can be found at soliqua100-33.com. Xultophy 100/3.6 should be available in the US very soon and the manufacturer, Novo Nordisk, will likely have programs to support its use. Both new fixed-ratio combination products provide people with type 2 diabetes and their providers with a treatment option that is convenient, easy-to-use, and works to safely improve glucose control by combining two medications with different mechanisms of action in one pen device.
The pain of insulin injections is well-documented, and the diabetes community is always searching for better alternatives. One such promising technology is the long-awaited OneTouch Via, an insulin patch pump from Johnson & Johnson subsidiary Calibra Medical.
Designed for both Type 1 and Type 2 diabetes, the OneTouch Via is a very small (2 x 1 x 0.25 inches) patch pump that stores up to 200 units of prandial (aka fast-acting) insulin, which can be delivered by discretely pressing two mechanical buttons on both sides of the pump. It can be worn for up to 3 days, and would be used in combination with basal (or long-acting) insulin.
A replacement for Multiple Daily Injections
Both doctors and patients dread starting multiple daily insulin injections (aka MDI). It means more painful pokes, more potential for public embarrassment, and more opportunities to forget a dose of insulin. Thanks to new classes of non-insulin therapies (eg Victoza, Trulicity, Invokana, etc), starting mealtime insulin can often be prevented or delayed, but millions of people with Type 2 diabetes (and all with Type 1) will still require MDI.
Mealtime insulin usually requires carrying around insulin injection supplies (insulin pens and needles or vials and syringes) and injecting before meals, which can be embarrassing and/or cumbersome. Traditional insulin pumps present their own challenges, as most have long tubing and complicated electronic interfaces that are not user-friendly.
Similar to the V-Go from Valeritas, the OneTouch Via is an entirely mechanical, tubeless, and disposable patch pump. There is no screen or complicated electronics, which keeps costs down, and makes for an easy-to-use interface. The user just presses two buttons down at the same time to deliver mealtime insulin, in 2 unit increments. This can be done through clothing, so a user could easily and discretely take 12 units (as an example) with six button presses done through their fabric.
Another advantage for both types of diabetes is that the OneTouch Via allows users to easily take additional boluses, for small snacks or hyperglycemic episodes that would otherwise require a new injection.
In study data shared at the 2016 American Diabetes Association Meeting, users wearing the OneTouch Via reported injecting mealtime insulin 50% more often than they had previously done with pen or vial, and 88% of them reported that they worried less about forgetting insulin injections.
Unlike the V-Go, the Via can be worn for 3 days and stores up to 200 units (the V-Go stores only 36units and must be changed every day). Also unlike the V-Go, the Via only replaces mealtime insulin and should be used in conjunction with basal (long-acting) insulin.
The Rocky Road Ahead
As the marketing efforts for inhaled insulin and the Valeritas V-Go have shown, replacing mealtime insulin injections in market and mindshare isn’t as easy as one would expect.
While 75% and 100% of providers in the previously mentioned study preferred the Via over insulin pens and insulin syringes respectively, providers in the community can be slower to adopt and more wary of newer technologies.
Also, adhesive patches and wearable devices are not the ideal solutions for all people. Patients can develop skin reactions to the adhesive or feel burdened when a device is stuck to their body, no matter how small.
Perhaps in light of these concerns, the OneTouch Via had been previously slated for release in early 2017, but now might face delays in light of JnJ’s recent intentions to explore the sale of their diabetes division.
So you’ve read all the headlines about an artificial pancreas and how it’s supposed to change the world for diabetes, but what does it really mean? We understand the skepticism… Remember: Medtronic previously claimed to have released an artificial pancreas system back in 2013.
But this time, the Medtronic 670G actually is a big deal. It’s a major step forward towards the artificial pancreas, and scientific studies back up its bold claims. (Note: it is NOT a true artificial pancreas, though)
But instead of repeatedly saying how important it is, we’re going to tell you exactly why it matters.
An “artificial pancreas” is like a “self-driving car”
The quest toward an “artificial pancreas” closely parallels that of the “self-driving car.” The names do a good job in describing their futuristic vision, so long as you understand that the pancreas is the body organ that produces insulin. (In Type 1 diabetes, the pancreas no longer functions properly and stops making insulin, causing blood sugar to go out of control.)
So continuing the comparison, having Type 1 diabetes is like owning a car with just an engine; no steering wheel or brake. Not good. Thanks to modern medicine, people with diabetes have the opportunity to “drive their car” by checking their blood sugar and injecting insulin appropriately.
Much like a self-driving car, a true artificial pancreas would be an autopilot for navigating the highs and lows of blood sugar. With an artificial pancreas, the user would not have to devote any effort to controlling their blood sugar. It would take care of itself, just as a self-driving car would get you from point A to point B on its own.
But now the next question…
Is the Medtronic 670G an artificial pancreas?
No, but it’s halfway there. If a true artificial pancreas is like an autopilot for self-driving cars, the Medtronic 670G is similar to “adaptive cruise control.” (If you don’t know what that is, adaptive cruise control allows a car to automatically accelerate and decelerate to maintain a safe distance from the car in front of it). If you want to drive on a straight stretch of road without making any lane changes, adaptive cruise control requires virtually no user interaction.
Similarly, the Medtronic 670G’s breakthrough feature adjusts basal insulin delivery (by speeding it up or slowing it down) to maintain a normal blood sugar of 120 mg/dL. It might not be as obvious during the day with meals and periods of exercise, just as adaptive cruise control plays a more subtle role when making many turns during city-driving.
But overnight and between meals is when the 670G’s adaptive cruise control truly shines, when circumstances are relatively stable, without the need to “change lanes” for meals or exercise. And keep in mind, unlike a car that you only use for trips, people with diabetes live with their disease 24 hours a day, 7 days a week. So a significant portion of their day is spent during those in-between and overnight periods.
Medtronic 670G’s “Adaptive Cruise Control” Works
Studies have clearly shown that wearing the 670G improves sugar control by reducing time spent in both high and low blood sugar range and lowered average A1c from 7.4% to 6.9%.
People who have worn insulin pumps with “dynamic cruise control” features particularly rave about its benefits on improved sleep overnight. Restful sleep is a big deal (and why mattress/pillow companies make a killing!), and it’s even more elusive with Type 1 diabetes due to the fear of overnight hypoglycemia or hyperglycemia. It’s not uncommon to be woken up several times a week in the middle of the night to check blood sugar or to have to eat a snack to avoid hypoglycemia. And even when sleep is not interrupted, waking up with higher or lower sugars than desired can start the day off with a thud.
As you can see in the graph above, adults using the 670G algorithm (highlighted in red) had a much narrower range of blood sugars, especially at night, when compared to standard pump users (the shaded grey area). They also headed into their mornings closer to target, and with a more stable glucose trend.
Medtronic 670G is just the beginning…
The top reason we’re excited for April 2017 (when the Medtronic 670G becomes available) is that it is just the first of a wave in the movement towards a true artificial pancreas.
While Medtronic has the advantage of manufacturing both its CGM and insulin pump, many future competing artificial pancreas systems are partnering with Dexcom’s highly rated, iPhone-compatible continuous glucose monitors.
The long list of such artificial pancreas systems includes a variety of approaches such as Bigfoot’s iPhone-based user interface, the more altrustic public benefit company BetaBionics’ iLet, and collaborations between Tandem and TypeZero.
These projects are in various stages of advanced development, most of which are being currently worn and tested in clinical trials and research labs. The initial feedback of test subjects has been exceedingly optimistic, and the future of the “self-driving” artificial pancreas is just around the corner.
No matter which company (or companies) win, the type 1 diabetes community is the biggest winner.
Stay tuned for more coverage of the Medtronic 670G and other artificial pancreas devices…
The diabetes community has been set ablaze after UnitedHealthcare announced an agreement for Medtronic devices to be the “preferred” in-network, durable medical equipment (DME) provider of insulin pumps. Starting July 1, 2016, UnitedHealthcare patients will be funneled toward using a Medtronic insulin pump instead of offerings from manufacturers like Tandem and Animas.
Many diabetes advocates have eloquently voiced their outrage and have been rallying under the hashtags #MyPumpMyChoice and #AccessMatters, and I strongly echo their sentiment that this policy puts “profits before patients”. It’s unacceptable, and both UnitedHealthcare and Medtronic deserve any negative publicity that results from such a short-sighted decision.
To add another layer to the discussion, though, what I find particularly insightful about the controversy is that it highlights the distinction between medication and medical technology. I rarely blink an eye when my patient has to switch brands of insulin, so why is it such a big deal when they have to switch brands of insulin pumps?
Technology is Intensely Personal
Whether it’s Apple vs Samsung, Xbox vs Playstation, Nikon vs Canon, or BMW vs Mercedes, fierce loyalties are found among their users. Beautiful photos of phones and smartwatches adorn billboards across the city, evoking emotions such as envy and desire in a way that no medication can.
When buying a new device, there’s a curious sense of satisfaction when finally choosing a model after poring over reviews and comparing individual specifications. Making that choice creates a personal connection before it even arrives in your hands.
On a personal level, many of my most touching diabetes patient interactions are due to technology. A recently-emigrated woman came to my office and was overjoyed to find that she could obtain an Omnipod pump, as it hadn’t been allowed by her previous nationalized health system. Additionally, I love watching the eyes light up in patients and their family members when they first learn about continuous glucose monitoring (CGM) and the ability to view their blood sugars on their phone.
In diabetes, harnessing technology to manage a chronic condition brings a sense of empowerment that medications alone can never do. Removing the ability to choose medical devices only adds to the sense of helplessness that underlies too many other aspects of diabetes.
Technology is Defined by Interaction
For medications, pharmaceutical companies create chemical compounds that elicit a desired physiologic effect. Their competition will create a slightly different chemical compound with a similar mechanism of action, and these medications are grouped into the same class (eg Humalog and Novolog insulin). For the most part, they are interchangeable to patients and providers, and insurances frequently prefer one over the other. No big deal — just swap out one pill (or pen/vial) for another.
But for devices, focusing on the desired outcome only tells a portion of the picture. For reference, choosing a smartphone is about more than making phone calls and browsing the web. As Apple’s success has shown, the overall user experience of gadgets often matters more than functionality. The iPhone was not the first smartphone (remember Blackberry?), but its intuitive and simple user experience expanded the smartphone audience from working professionals to college students, children, the elderly, and everybody in between.
When using an unfamiliar smartphone or computer operating system, even a simple task like sharing a photo can seem Herculean. With health technology, the stakes are exponentially higher as potentially lethal medications must be managed by complex user interactions with software dashboards and calculators. Being forced to switch between differing interfaces of insulin pumps and other diabetes technology creates confusion/frustration at best, and gaps in diabetes management at worst.
Put simply, there are no “class-equivalents” in the world of devices because they encompass a complex interplay between software and hardware. A Medtronic Pump is as similar to a Tandem Pump as a Blackberry (they still exist!) is to an iPhone.
Competition breeds innovation
To be clear, the outrage isn’t regarding the quality of Medtronic’s insulin pumps, or whether they are inferior or superior to the competition. Rather, the issue is that eliminating competition and choice in the insulin pump market stifles creativity and innovation.
We live in such an exciting time for diabetes technology. For insulin pumps alone, there are touch-screen pumps (Tandem), tubeless patch pumps (Omnipod), color screens (Tandem, Omnipod, and Animas), and cartridge-based pumps (Asante). Each of these features are appealing to different types of users. It’s not one size fits all.
Evidenced by Tandem’s 20% decline in stock after the UnitedHealthcare announcement, it’s hard to believe that such product diversity would exist in a world where insurance companies anoint a winner. Would Android and iPhones have come as far as they have if wireless carriers “preferred” Apple and required a prior authorization for any Android phone?
In the above timeline, notice that Medtronic Insulin Pumps did not noticeably upgrade their user interface for over 10 years… until after the 2012 release of the Tandem T: Slim. Now, the upcoming Medtronic 640G incorporates a dramatic redesign that seems to take some design cues from its competition. Had the Tandem never come to market, I suspect that the next Medtronic would look similar to the previous generations.
Deeper implications beyond diabetes
The digital health revolution is underway, and the future of health technology includes fascinating devices like wearable (or even implantable!) sensors and novel drug-delivery mechanisms, affecting specialties from psychiatry to pain management.
I’ve often beaten the drum that diabetes technology has been a harbinger of the future of health technology (continuous glucose monitors preceded the current infatuation with wearable sensors by about 10 years), and this week’s news suggests a bleak future where established, larger device manufacturers can outmaneuver innovative disruption by strategically partnering with insurance companies.
Free markets and capitalism have been serving the best interests of technology consumers for decades, and such interference by insurers would negatively impact health devices in all areas of medicine.
Call to Action
So what should we do? Make your voice heard, and raise awareness of the issue by sharing posts like this on Facebook and Twitter. Reach out to the pump manufacturers, tell your doctor, and vocalize your displeasure to the insurance companies. DiabetesMine has compiled a helpful list of action points here and will continue to cover the issue as it develops along with other advocacy sites like Diatribe.
As the world of glucose meters have shown, it might be a UnitedHealthcare-Medtronic partnership now, but what’s to prevent UnitedHealthcare from switching to a different pump manufacturer when their current agreement expires?
That’s why we must act now and make it clear that we will not take it lightly when insurance companies try to dictate which medical devices we use and prescribe.
On Tuesday, Mannkind announced that Sanofi will no longer market and distribute inhaled insulin Afrezza, effectively ending any current long-term plans for availability on pharmacy shelves (Mannkind plans to continue marketing the product, potentially with a new partner).
What happened? How could such a promising medication (“insulin without needles!”) come and go without causing a stir? Where is the patient-led petition and outrage? Where’s the Kickstarter campaign to revive Afrezza?
Great Idea, Not Great Sales
Afrezza had a lot going for it. This goes without saying, but inhaled insulin eliminates the need for multiple painful injections of rapid-acting insulin every day. Also, unlike the failed inhaled insulin Exubera which was comically large and bore a striking resemblance to drug paraphernalia, Afrezza is small and fairly discrete.
And unlike Exubera, Afrezza’s technosphere delivery method offers better absorption when compared to the most widely-used injectable rapid-acting insulins (humalog, novolog). Faster peak action and faster exit can potentially flatten the “rollercoaster” of glucose peaks followed by valleys when bolusing for a meal.
As such, I’m sure countless focus groups and market research surveys had respondents voicing their enthusiasm for a “painless” insulin. But once Afrezza hit store shelves, the sales fell painfully short of expectations.
High Barriers to Entry for Patients and Providers
We are all creatures of habit, and patients and providers alike are well-versed with injectable medications. Swapping one brand of insulin for another (e.g. humalog for novolog)? No problem. However, inhaled medications are foreign to patients and the providers who manage diabetes (endocrinologists, PCP’s, diabetes educators, etc). Additionally, a test (spirometry) that is not commonly performed by diabetologists needs to be performed prior to starting Afrezza. It’s understandable why doctors aren’t prescribing Afrezza. Other non-traditional insulin delivery mechanisms such as the Veritas V-Go face a similar uphill battle of educating consumers and providers and maintaining “mindshare”.
Similarly, for a person with diabetes already on multiple daily injections, Afrezza did not offer a simple “plug and play” solution. By coming in only two doses set of 4 and 8 unit cartridges, dosing was intimidating for insulin-sensitive patients requiring just 2-3 units at a time and inadequate for insulin-resistant patients requiring more than 10 units per administration. Also, the coughing and dry throat that many new users experienced was off-putting.
In contrast, consider the potential of a theoretical oral insulin. Without any additional testing, education, or caveats, such a solution would be a guaranteed hit.
An Incomplete Solution: Basal Injections Still Required
As eloquently stated in this post-mortem analysis of Exubera by Dr. Lutz Heinemann, inhaled insulin only replaces fast-acting (or prandial) insulin injections, leaving patients to continue their long-acting (or basal) insulin injections.
Many patients with Type 2 diabetes are only on basal insulin, but very few exclusively take prandial injections. As such, most Afrezza users would still have to carry around their injection supplies for their daily or twice-daily lantus (or levemir, etc) injections, in addition to their inhaler supplies. One could also argue that a quick insulin pen injection under the table is more discrete than raising an (albeit small) inhaler to the mouth.
In my practice, some of my patients requested samples or a limited supply of Afrezza to try out or use as “supplementary” to their basal and prandial injected insulin, but patients rarely completely switched from injected rapid-acting insulin to inhaled insulin.
Afrezza: A Solution in Need of a Problem?
Is the allure of pain-free insulin as great as it initially sounds? To onlookers, insulin injections look painful (which I’m not disputing!), but I’m frequently told that the pain from glucose meter fingersticks far exceeds that from injecting insulin.
And Dr. Heinemann also raises a valid question: is it the pain of insulin injections that people fear more, or is it the stigma of insulin and its association with weight gain, poor control, and risk of hypoglycemia? Many patients with Type 2 diabetes who are reluctant to start once-daily injectable insulin are completely fine with injecting Victoza, thanks to its association with weight loss (and TV marketing campaign).
So with Afrezza: who exactly is it for? There are small segments of the diabetes population who would definitely benefit: 1) those who absolutely refuse injections of any kind and 2) those who require an insulin with faster peak and faster clearance from their system. But for many people with diabetes, Afrezza is no more than a novelty.
Why do you think Afrezza hasn’t been successful thus far? Share your thoughts in the comments!