"Is my insulin bad?"
I've asked this question so many times over my 34 years with type 1 diabetes -- when I notice no matter how much I dose, it isn't lowering my blood sugars and it feels like I'm just injecting water.
Sometimes I had kept my insulin vials outside the fridge for weeks, or it was delivered on a hot summer day and sat outside on the front porch for hours while I was at work -- without adequate ice packs and despite the fact that the package was supposed to be delivered to my office.
Or there were times at the drugstore when the pharmacist couldn't find my insulin in their cooler, but rather found it sitting out at room temperature for an unknown period of time. Could this be the culprit?
All this uncertainty has been on my mind lately, after seeing a scientific study that poses questions about insulin concentration and potential problems with the cold supply chain. In layman's terms, that means the quality of insulin isn't up to par by the time it reaches patients like me.
But hold up -- it's not worth getting all panicked yet, because as of now, it's not clear whether this study can or should be taken at face value due to the limitations that exist with how it was conducted. Even the authors admit that, but still many authorities agree that the topic of insulin quality and integrity is something we all should be concerned about and further explore, to assure that it isn't impacting diabetes outcomes on a regular basis.
Surprisingly, the American Diabetes Association (ADA) responded to this study by issuing a statement that basically dismisses the results and essentially says, "trust us, this isn't an issue."
This ruffled feathers, especially among those who believe the ADA's acceptance of Pharma funding influences what it says and does. We aren't convinced of a conspiracy, but do have concerns about this insulin concentration issue and believe it needs more research -- and it's disappointing the ADA doesn't acknowledge that.
"Bottom line is we owe those with diabetes our best efforts in finding as many answers as possible," says Dr. Alan Carter, principle author on the controversial study. "Assuming the insulin is always good is a nice place to be, until it’s not..."
The Insulin Concentration Study
Published on Dec. 21, 2017, this study looked at older insulin brands, R and NPH (made by Lilly and Novo as the predecessors on the market before analogue insulins debuted in the later '90s).
Those behind it are: Dr. Alan Carter, of the non-profit MRIGlobal research group and a pharmacy professor at Univ. of Missouri-Kansas City; and Dr. Lutz Heinemann, a San Diego-based expert on insulin and emerging biosimilars.
They randomly picked up 18 vials of insulin and stored them in a research lab at the appropriate temperatures, before discovering that the concentrations weren't adequate. Insulin vials and cartridges are required by the FDA to contain 95 U/ml of insulin when they're sent out by the manufacturer. Regulators also require proper handling and temperatures in order to maintain the quality.
But when Carter and his team examined the insulin they'd purchased, the vials ranged from 13.9 to 94.2 U/ml, with a mean of 40.2 U/ml. No vial was at the minimum FDA-required standard of 95 U/ml. Here's a link to the full paper.
Carter says the supply chain may have an impact on insulin quality that could affect glucose control.
As to how they reached those study results, Carter says they were "acquired using new technologies that are very precise and have been used for detecting intact insulin in plasma, but have not been validated by any regulatory agency for measuring intact insulin concentrations in vials or pens. More work is needed to explore the reasons why the intact insulin was detected at reported levels... using this approach. Perhaps a different way may be better and still needs to be determined."
The researchers are working with the Diabetes Technology Society to do more research here, especially with more modern insulins that exist on the market today. Carter says the DTS is helping to organize a panel of diabetes experts, PWDs, government agency officials, and insulin manufacturers to discuss this more in depth and explore the supply-chain on insulin more fully.
"In my opinion, as the market evolves to include biosimilar insulin options a uniform approach to monitoring quality when it reaches the person with diabetes should be developed and implemented," Carter told us. "How to cover the cost if such a system is a concern, (because) insulin is very expensive already. Not to mention that such a program would require unprecedented cooperation between a variety of interests. It may be like 'herding cats' but we believe a solid attempt should be made."
The ADA Response
In mid-January, the ADA's Chief Science and Medical Officer Dr. William Cefalu wrote a blog post in response to the study. At the start, he expressed the ADA's "very serious concerns" over this research, but not the issue of insulin concentration itself.
The ADA specifically calls out the extremely small sample size, and the methodology used, and points out that it (ADA) consulted "clinical and biochemistry experts" and found the results were inconsistent with their own findings and real-world examples.
Additionally, the ADA noted that it consulted with insulin manufacturers and saw no reason to suspect they are at any fault based on quality control procedures mandated by the FDA.
"Based on these findings, we have no reason to believe that the results of Carter et al.’s study reflect the actual potency of human insulin widely available at retail pharmacies in the United States," Cefalu wrote. "We strongly urge patients to talk with their doctors and pharmacists about any concerns they have with their insulin or diabetes treatment plan."
DiabetesMine asked the ADA to expand on its initial statement or clarify parts of it, particularly on whether the organization sees a need to explore this further, but received no response.
If Insulin Is Bad...
Now, of course, no one can deny that sometimes insulin isn't OK. It happens. Many of us have experienced that firsthand, for whatever the reason.
If and when that happens, a few things to be aware of:
Pharmacies: They don't all have blanket policies on what they'll take back, but most do -- whether it's local walk-in pharmacies or mail-order companies. You would need to explore their return/refund rules which can often be found online. Some may also argue, but you can fight back, with the help of your doctor, who you can ask to contact the pharmacy to attest that your batch of insulin is ineffective.
Insulin Makers: They have troubleshooting programs in place and are pretty good at replacing potentially bad insulin. For example, here's a page on this from each of the three big insulin makers: Eli Lilly, Novo Nordisk, Sanofi.
Regulators: Yes, the FDA also regulates the supply chain from the manufacturer to the supplier, where it travels before ending up in the patients' hands. The agency has a whole Drug Supply Chain Integrity division, where patients can read up on all the laws and requirements and also report suspected issues we've observed. There's also the MedWatch reporting system online.
UPDATE: Follow-Up Research on Insulin Quality
Interestingly, since this issue started gaining more attention in early 2018, researchers and diabetes orgs have been keeping tabs on this with their own studies.
At the big European diabetes meeting in early October 2018, researchers presented a head-scratching study showing that insulin stored in domestic refrigerators is often not stable and can negatively affect insulin's quality and potency. Yikes! That research showed that insulin was frequently outside of the Pharma recommendations on temperatures 11% of the time on average, and freezing was also a common issue. Of course, before anyone panics, that study needs to be taken with a grain of salt because it was commissioned by MedAngel, a small startup that sells an insulin temperature monitoring device...
In October 2018, the D-org trio of ADA, JDRF and Helmsley Charitable Trust announced they'd be funding a new study to analyze insulin purchased at pharmacies. This is a specific follow-up to the small study Carter conducted late last year. In a news release on this, the orgs announced they'd be providing funding for the University of Florida to conduct a one-year study examining this issue. Led by Dr. Timothy Garrett and other international experts, this will examine 8 insulin formulations with varying action-times, and the study will happen across five U.S. regions using different protency testing methods. They expect the research will be published by mid-2019.
We'll look forward to seeing the results of that study, in providing more data on this important topic so those of us PWDs using insulin can make better decisions.
In a perfect world, the high prices we're forced to pay for medications such as insulin should be a guarantee that what we're getting is up to par. But sometimes, it's not. We can't blindly trust that it is.
If there's more information we can glean from scientific studies and questioning the system, then by all means everyone in the Diabetes Community should be embracing that -- including the organizations that proclaim to be all about science and research and patient protection, and btw continually ask insulin-using patients for monetary donations.