Inhaled insulin Afrezza is on its last breath. What happened?

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!

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