Anyone going on a brand spanking new insulin pump is probably filled with anticipation and excitement, but there’s always a little bit of trepidation when it comes to a new piece of medical technology. Will it meet my needs? Will I like using it? Most importantly: will it work? The fear of potential problems like motor error, malfunctioning buttons, and occlusions can throw a wrench in anyone’s pumping anticipation.
Apparently, those wrenches have been flying around the Diabetes Community quite a bit lately, especially last summer when the newest insulin pump hit the market.
We have discovered dozens of new Tandem t:slim users who’ve taken to the Internet, reporting on blogs and social networks that their pumping honeymoon swiftly 
came to an end with the onslaught of occlusions using Sanofi’s Apidra insulin. Naturally we wondered what could be the cause, whether or not this was strictly a t:slim issue, and whether or not there is anything anyone can do about it.
About Occlusions
Occlusions are basically just blockages that prevent insulin from being delivered. If you have a blockage, pressure will build and usually your insulin pump with alarm, letting you know something has run afoul.
“There are several reasons why they happen, ” says Dr. Brian Levy, an endocrinologist and Senior Director of Clinical Affairs at Animas. “They include kinking of tubing that goes from the pump to the insertion side, or more importantly, the kinking of the catheter. Most cannulas are made of Teflon or plastic which can kink. It can also be due to problems at the insertion site, inflammation that can happen around the insertion catheter or the presence of scar tissue. If a patient uses the same place on their abdomen, there can be chronic build-up of scar tissue.”
Occlusions can and do happen in all insulin pumps, whether tubed or patch pumps, and they have happened with all three types of fast-acting insulin on the market.
But a 2008 research study published in the Journal of Diabetes Science and Technology showed Apidra had the highest probability of occlusions in pumps over five days (despite the FDA’s recommended site changes every 2-3 days). That was comparing Apidra to both Humalog and Novolog, although the probability of an “early occlusion” occurring during the first 72 hours was actually highest in Novolog.
In a 2010 study of the optimal usage of insulin pump sets, published in that same journal, researchers found that during the 48-72 hour mark occlusions occurred independently of the insulin used. However, that study only involved in 12 patients and the authors even note that occlusions are rare.
Apidra vs. t:slim?
The issue at hand is that after Tandem released the t:slim last summer, some new users started noticing something curious. Occlusions started occurring. A common theme: all the patients used Apidra.
Image from Sweetly Voiced
Melissa Lee, a type 1 PWD in Texas, said that she started noticing the problem early on. “As early as my second cartridge,” she says.
Another longtime type 1, Bernard Farrell in Massachusetts, who’s one of our resident tech gurus in the Diabetes Online Community, jumped on the t:slim boat early on and discovered the exact same problem. Both he and Melissa have since switched insulin brands, both to Humalog.
We also heard from D-Mom Jodee Martin, whose 13-year-old son recently went on the t:slim. After speaking with Tandem, she speculates that, “Apidra may not be compatible with the pump. The makers of Apidra suggest that Apidra be changed every two days in this pump, so that may be the problem but our whole reason for getting a pump with a 3ml cartridge was so that we could change every third day.”
We contacted Tandem to see if they had any ideas what was going on. Steve Sabicer, the company’s PR rep, says they’re looking into the issue, but are aware that Apidra is only indicated for 48-hour use in any insulin pump (!), based on that 2008 study showing Apidra had a higher occlusion rate in pumps over several days.
Due to this and what they saw as the limited number of users on Apidra, Tandem did not include Apidra in their clinical trials — but focused instead on the two most prescribed fast-acting insulin on the market, Humalog and Novolog, in its FDA submission.
Two-Day Limitation!!
What?! Apidra isn’t “indicated” for use more than 48 hours in any insulin pump? When pumps are clearly meant to last at least 3 days?
It’s true, confirms Sanofi rep Susan Brooks.
“Our Phase 3 pump submission for Apidra was 48 hours, therefore we are indicated for 48 hours,” she said. “When used as directed, Apidra has shown a low rate of pump clogs and infusion-site reactions.”
The reason? Back when Apidra was approved in 2004, it was standard for insulin to be approved for just 48 hours. Crazy, huh? It wasn’t until several years later — 2009 for Novolog and 2011 for Humalog — that the regulations were increased to three days for insulin in a cannula, and seven days for insulin in the pump reservoir (presumably because insulin degrades with heat exposure, and the body is quite warm).
We wondered why this fact is so under-publicized, leaving patients to learn about this limitation the hard way?!
Furthermore, Sanofi has no plans to seek approval for a 72-hour use of Apidra, Brooks says, so that means we won’t get any official answers about what happens to Apidra after three days.
Who’s Warning Patients?
It doesn’t seem that Sanofi has really stepped up to make this limitation clear to patients, but what about the pump companies? You’d think they’d at least want to warn patients of this possible fail in advance.
We contacted Animas, Medtronic and Insulet to find out if they’d experienced any recurring issues with Apidra insulin, or were alerting patients to potential problems. None of them would comment other than a canned statement that “when used as directed,” there should be minimal issues with occlusions no matter what insulin is used.
Uh huh, right. Just what PWDs want to hear when problems occur — it’s our fault. Grrr.
Sean Gallagher, senior director of marketing at Insulet Corp., did clear up one thing: he says the pump companies “are not required from a regulatory standpoint… to test with different insulins for performance.” Right — so if it’s not required, why would any company invest in this?
On the flipside, the insulin companies aren’t required to test their products in every pump on the market either. It turns out the only pumps that Apidra was studied in during their FDA clinical trials aren’t even made anymore — the Disetronic H-Tron plus V100 and D-Tron with Disetronic catheters (Rapid, Rapid C, Rapid D and Tender) and the Minimed Models 506, 507, 507c and 508 with MiniMed catheters (Sof-set Ultimate QE, and Quick-set). Medtronic doesn’t even produce those models anymore, and of course, Disetronic was acquired by Roche and has now morphed into the Accu-Chek Spirit.
Basically, occlusions happen in every insulin pump and with every kind of insulin, and there are plenty of patients who have managed to use Apidra in their t:slim without an issue — but we find it interesting that the only pump company to publish an official statement about using a particular insulin is Tandem regarding Apidra:
“The t:slim Pump is indicated for use with Novolog and Humalog, but we have no reason to believe that there is anything in the t:slim’s pumping mechanism that could contribute to a higher incidence of occlusions using Apidra. There are distinct labeling differences between rapid-acting insulins and their use in pumps, particularly as it relates to how frequently the reservoir should be changed. These are things you should discuss with your physician as part of your decision process.”
Some folks wonder if there’s something about the t:slim in particular that doesn’t host Apidra well. One theory, posed by Manny Jimenez, the Tandem customer service rep that Melissa spoke to, is that there is no information about how Apidra responds to the pressure of the t:slim’s unique microdelivery chamber, which is an interior bag that is pressurized versus the traditional plastic cartridges that hold insulin.
No one has vetted this theory, and they probably won’t any time soon. I guess this means we’re back to being guinea pigs…
Just Call Us ‘Guinea PWDs’
On her blog Sweetly Voiced, Melissa shared that when she used Apidra in her t:slim, the majority of occlusions happened after 48 hours, but she is not having any occlusion issues at all now on Humalog going for the full three days of usage. That’s the same finding Bernard came up with, when changing his insulin routine.
Dr. Levy, who also practices as an endocrinologist in addition to his work at Animas, says he hasn’t seen any issues with his patients using Apidra in their insulin pumps, but he notes that ”the longer one wears an insulin pump without changing the catheter, the more likely an occlusion will occur.”
On that note, Insulet’s Gallagher shared this slide showing how your BG creeps up the longer you keep your pump on:
“This is exactly why instructions for use to change their insertion site every 72 hours,” Dr. Levy says. “And we know that many patients do not, for many reasons. It could be cost, or it’s a pain to change the insertion site, or forgetfulness. So that’s probably the most common reason why there is an insertion site issue.”
When it comes down to making a decision on what to do, we PWDs just need to carefully consider our priority preferences for pump models and type of insulin — and if we aren’t willing to compromise on one, we may find ourselves changing our pump sites every 48 hours.
{Editor’s note: Amy uses in Apidra in her Omnipod, and actually does need to change her site every 2 days; looks like we may have discovered the explanation for that.}
Most insulins today have a phosphate buffer to prevent occlusion.
Apidra does not, while Novolog and Humalog do.
Way back in the day, when pumping was not so mainstream, pumpers would have to use a special formulation of regular, called “buffered regular”, which was a phosphate-buffered insulin, to prevent occlusions.
The problem associated with occlusions is that the insulin actually crystallizes. Insulin buffered with phosphate prevents this from happening.
I think it takes a set of circumstances for there to be a problem using Apidra in a pump. I’ve used Apidra in my cozmo for about 3 years, I get one occlusion per year, if that.
I am type 2, I have a higher basal rate than most type 1′s would have. That may make a difference.
I live in a cold climate, that may or may not make a difference.
I don’t use a t-slim. That may or may not make a difference.
I think that like most things diabetics deal with, trial and error is involved.
Apidra works much faster than Humalog and Novolog for most diabetics, if you digest food quickly this can be a big advantage.
It’s worth a try
-Lloyd
I found this to be an interesting read. My best success has been with a two day rotation. The site has no blood leaks when the inset is removed and there is minimal visual damage at the prior inset site and no issue with occulsions. My issues have come from bends with the internal inset location. The rise in glucose after a new change is a clear signal that there is a bend. Another factor is related to the ability of the inset tobe in a “locked” position”. Meaning there is no play at the inset site due to an up and down motion based upon body movement. Being re-stuck at the inset site can hurt. As always have a great day.
Dab
I have used Apidra with the Animas One Touch ping for a couple of years with no occlusions. I change the site every 3 days.
We have tried all 3 insulins in my daughters Animas Ping pump. We prefer Apidra. It’s faster acting and it seems to work so much better for her. We change her site about every 3 to 4 days. She had what seemed to be endless highs with Novalog and Humalog stings terribly bad every time we bolus. We’ve yet to have an occlusion (knock on wood)!!
I would encourage people to try all the insulin options to see what works best for them.
I’ve actually been using Apidra in my t:slim for over a month without issues and I change out sites every 3days
I have been pumping for 15 years using MM and Silhouettes and either Novolog or Humalog the entire time. I can’t comment on Apidra since I’ve never used it.
I can comment on site rotation.
I have never abided by the 3-day rule. I use each site for 7 days on average. I have never had a problem and my a1c’s have never been above 6.5 (often lower.)
And while there have been “studies” suggesting dire consequences for exceeding three days, it’s also true that most, if not all, of those analyses are suspect. The one cited in the story above, for example, was underwritten by Unomedical. That company sells Silhouettes and other infusion site so there’s a blazing conflict of interest to factor into any conclusion. The shorter the duration, the greater the sales.
And sure, the work may be valid. But I covered the tobacco wars years ago when supposedly independent researchers insisted nicotine was not a drug. Some even asserted it wasn’t addictive.
That’s a big of a false parallel, of course. But the caution is not. Read these studies with skepticism.
Make your own decision based on your own results and history. It’s possible that screwy numbers are the result of something else – bad decisions on food, for example, and not site rotation. Yet rotation is an “easy” and satisfying fix.
Caleb’s been using Apidra in his Pods since 2010 and since using it has changed his Pod every other day. Been meaning to post about this experience ever since. Maybe this will be the inspiration to do so…
I have had nothing but occlusions with Apidra in my Cozmo. I finally had to switch back to Novolog because I would get occlusions on day one of Apidra during the summer with everything swapped out (insulin cartridge, tubing, infusion site.) Only the rare occlusions with Novolog and those all seem to be infusion site related on the rare occasion they happen.
Thanks for a great article Allison.
I switched from Humalog to Apidra several years ago because I’d heard that it worked better for some folks. I noticed no difference in speed or duration from Humalog. At that stage I was using a Deltec Cozmo and changed sites every 3 days. If I forgot and went to 4 days I did see worse control on that last day.
Once i started on the t:slim I saw occlusions many times. Sometimes 3 in one week. Tandem changed the pump in case that was the cause. But I didn’t hear about the 48-hour approval for Apidra until I spoke with someone senior at Tandem. It was in the package insert for Apidra, but who reads those? Until my first shipment of Humalog arrived I went to 2-day site changes and the occlusions disappeared.
I have since switched back to Humalog and my occlusion problems completely disappeared. I didn’t change my settings from Apidra, YDMV. Note that I set my insulin duration to 5.75 hours. For me it may in fact be slightly longer.
I do wish Tandem support had brought the 48 hour Apidra ‘limitation’ to my attention earlier, but that was in the earlier days of t:slim support. I imagine this is the first question they ask folks who see occlusion alarms these days.
In the 1990′s before either Novolog or Apidra were approved “at all”, it was fairly easy to collect data on (let’s call it) infusion site failure, rather than occlusion. At the time, the only insulin-anaolg available was Humalog. First lets define the symptoms. Rise of bg’s after 24-48 hours. Bolus of more insulin does not help. Moving the site does help. For infusion sets such at the “tender” or “silhouette” where the infusion cannula can be seen, occasional redness around the cannula. Insulin Pumpers self reported data on this for several years and came to the conclusion that between 5%-6% of pump users had a sensitivity to Humalog but not regular human insulin. With the advent of Novolog, collecting this data became more difficult because pump users would switch brands and the problem would disappear. Since that time there has been enough anecdotal reporting to strongly indicate (in my opinion) that the sensitivity to insulin-analog is general in nature and is probably 5-6% of pumpers for ALL insulin-analogs, however any individual person is usually only sensitive to one of these molecules. This is somewhat to be expected since the three fast-acting insulin-analogs (Humalog, Novlog, Apidra) all have slightly different molecular structures.
So, with respect to the findings reported in the article, I assert that they are meaningless because the sample size is way to small. A study with a dozen individuals would be badly skewed by having a single individual member with a sensitivity to the particular insulin-analog product. I am not saying that this problem does not exist, quite the opposite. For years I have said that this phenomena does exist. The problem is that no study with a large enough sample size has been conducted to properly characterize what is going on. To do so would require a study with at least 500 participants for EACH insulin-analog product PLUS a control group of the same size. That would provide a statistical meaningful outcome.
Michael Robinton
Executive Director
Insulin Pumpers.
Visit us at: http://www.insulin-pumpers.org/
Thanks for the post. I think it is important to get this info out there. Though, I switched my daughter to Apidra last week and I couldn’t be happier. We are starting to pump next week and I was fully aware of the fact we would have to do change sites every 48 hours (thanks to the DOC). It is still worth it. Apridra works so much faster and keeps my daughter’s blood sugar so much steadier. Great results in 1 week. She was on Humalog which was taking up to 5.5 hours to finish working. I am still so happy we found apidra.
I have been using Apidra in my MM Paradigm for over a year now. I switched to Apidra because my endo said it should help with the scar tissue buildup. I have had no problem with occlusion, but I never keep mine in for longer than 3-4 days.
Like Stella, I’ve been using Apidra in my MM Paradigm for a few years and have NEVER had a problem. No occlusion, ever. In fact in my 15 years of pumping I don’t think I’ve ever had a problem with occlusion. I also change my site about every 3-4 days. I think that, as Mr. Robinton said, the sample size is too small. However there are quite a few people here who are corroborating the results, so maybe we are wrong!
Yes, we have noticed some very high blood sugars since using Apidra the past few years…. that is offset by the speed in which corrections take place. We can get a high blood sugar down much quicker with Apidra. Apidra often lasts three days in her pump and often will fail at 2.5 days. We deal with it. Because the duration of Novolog is close to five hours and the duration of Apidra is 3.5 hours… for her. Most people have a four hour duration with Novolog and Humalog. If you should have a site failire, you will go much higher much faster but we knew that going in. We love Apidra. Use MM Revel pump though. If we had a 4 hour duration with Novolog there we would still have tried Apidra. The faster the insulin the sooner it is out of your system, the better, for bolus purposes for sure.
Going to have my pump fitted today … Eek all a bit scary !
Sarah, which brand/style tubing/infusion sets do you use? I’m a frustrated t:slim user trying to get Apidra to work because its the only fast acting insulin my body responds to. I get occlusions in 30-33 hrs like clockwork. I use cleos. Also wondering: Is shorter tubing supposed to decrease likelihood of occlusion (anyone)? Thank you!
i’ve used apidra for past few months and actually find i’ve had less highs and no occlusions compared to novorapid
When I went to an Onmipod pump from Medtronic, my diabetic educator told me that Apidra had fewer occlusion issues due to no zinc, so I tried it. I had distasterous results! Not disasterous due to occlusions, but because Apidra is extremely temperature sensitive and would quit working after day 2. I have since spoken to numerous diabetic educators about the subject. All of them reported bad issues with Apidra due to temperature sensitivity and said that was the reason for the 2 days FDA approval. I wne back to Humalog and have not had any issues since.
Been using the paradigm on Apidra in 90 degree weather this week with no issues. At least with the paradigm, Apidra is not a problem. Been getting 4 days out of it and great control. It’s too bad the t:slim can’t produce the same result (at least, for me).
I have a Medtronic. My endo switched me from Humalog to Apidra a few years ago citing occlusions as the reason even though I’d never had one. On Apidra I get an occlusion at least once a month, often more frequently. Guess I’ll ask my new endo about switching back to Humalog.
I have a Medtronic Revel pump and I have used Apidra since it first came on the market. I have never had an occlusion, but I am OCD about changing my infusion set every 3 days.