Me and NPH

As everyone knows, insulin prices are now criminal. For a long time I was using Levemir, just once a day, in the morning. It worked fine, as I don't seem to need insulin overnight. If I just stopped eating, I could eliminate insulin altogether, but that doesn't seem like a likely scenario.

For more than a year, I've been on Tresiba as part of a clinical study, which meant the insulin was free. That was nice. The Tresiba worked OK, but because it lasts for 24 hours, it meant I couldn't use as high a dose as I used for Levemir. I was on 20 units of Levemir but only 12 units of Tresiba. Any more and I'd go low overnight. In fact, even on the 12 units, I was going slightly low at night for long periods, according to the Freestyle Libre continuous glucose monitor (CGM) I was trying at my own expense.

When the Tresiba trial was over, I still had two Levemir pens that hadn't quite expired, so I used them. But when I found out that refilling my 3-month prescription would cost about $1000, I figured no way and  decided to try NPH. For the last week of the Tresiba trial, we'd been put on NPH, and it seemed to work OK, but my CGM stopped working after only a day on the NPH, so I was curious to give it a longer trial.

NPH is about $24 for a 10-mL vial of 100 units/mL at Walmart. So at 20 U/day, a vial should last me about 50 days, or 48 cents a day, $43 for three months.

On my Plan D, I actually pay only $30 for a 3-month supply of Levemir, but my plan pays $1359.40, and because the infamous doughnut hole is based on total drug costs, not what the patient pays, with those prices plus another expensive drug, I'd reach the doughnut hole for sure.

Other than expense, an important factor is how well it works. Two endocrinologists warned me that NPH is  unpredictable, that the same dose might work one way on one day and another on another. But I find that diabetes is unpredictable anyway. You can eat exactly the same thing and get the same amount of exercise on two days and get different results, so it's difficult to know which of the myriad factors that affect blood glucose (BG) levels is responsible.

Dr. Richard Bernstein, low-carbohydrate diet proponent and author of The Diabetes Solution, warns about using NPH because it contains protamine, which can interfere with the reversal of the anticoagulant heparin. But an endocrinologist I asked about this said he used NPH for years before the modern insulins were available and he'd never seen this problem, and besides, people these days tend to use other anticoagulants, so I decided not to worry about it. Anyway, I'd already used it in the clinical study.

Bernstein also says one reason the cloudy insulins seem unpredictable is that people don't shake the vials enough so the insulin isn't distributed evenly.

So what did I find?

NPH is definitely peakier than Levemir. Some sources say it peaks 4 to 8 hours after you inject, others say 4 to 6 hours, and the Joslin Diabetes Center says 4 to 12 hours (at least they're consistent with the 4). So there's obviously a lot of individual variation. I find it peaks about 7 hours after I inject. I get up early, usually around 5 am, and inject then, so my NPH peaks at lunchtime. This is handy, and I try to eat my big meal of the day at noon. If I don't have lunch, I might go low.

This is, of course, not the way you're supposed to use a basal insulin. You're supposed to inject just enough to keep your BG at a good level when you don't eat and then use a bolus insulin to cover meals. I'm too lazy to do that. And as a type 2 I have a bit of a buffer because I'm still producing small amounts of insulin, just not enough to cover meals.

Some people take a second shot just before going to bed to use the NPH peak to cover the dawn phenomenon. However, although my BG goes up a little in the morning, starting when I wake up, the rise is not large.

After the Tresiba study was over, I went back to Levemir until those pens were finished. Then, wearing the CGM,  I tried NPH, 5 units in the morning and 5 in the evening. Then I tried 10 in the morning. Then I tried 15 and then 20 in the morning. The 20 didn't make me go low except for once, and that was about an hour after I injected so it was probably not a result of too much insulin. Maybe I injected too close to a blood vessel. That happened with Lantus once, and I went down to 25.

Then for two days I tried no insulin, but the CGM gave out after just one day.

Then I got a new sensor and tried a few different concentrations.

The program you can use with the CGM calculates average BG each day. Here are what I got. When there's only one dosage listed, I took it first thing in the morning.

12 units Tresiba:  98, 105, 96, 91, 92, 103, 99, 96, 92, 89 (96.1 average with overnight lows )
15 units Levemir: 98, 104 (101 av)
20 units Levemir: 107, 89, 103, 104, 82, 94, 93, 100, 106, 110 (98.8 av)
10 +10 units Levemir (10 units in moring and 10 in evening):  90, 93 (91.5 av)
0 insulin: 114
5 + 5 units NPH: (5 in morning and 5 in evening: 118, 109, 103 (110 av)
10 units NPH: 102, 106 (104 av)
15 units NPH:109, 101, 96, 101, 109 (103.2 av)
20 units NPH: 101, 100, 109, 101, 99, 95, 97, 96, 86, 103, 93 (98.1 av)

Note: One problem is that the Libre is that every sensor can read slightly differently, and I find that they read high on the first day after insertion, so I don't use that day.

Thus the Levemir given twice a day gave the lowest average BG, but that was only two days and might not be reliable. Not surprisingly, the highest average was with no insulin, but that was only one day. The sensors and then the receiver kept not working at important times.

12 units of Tresiba gave the next lowest average BGs, but there were also a lot of overnight lows.

The 20 units of Levemir given in the morning, with lots of data points, and the 20 units of NPH given in the morning, with lots of data points, gave about the same averages, 98.8 and 98.1, respectively, and the NPH readings were with a sensor that read about 10 points high.

So FOR ME, it seems as if NPH works just as well as Levemir. Whether or not I'll continue with it permanently depends on how close to the doughnut hole I seem to be getting. It is a lot more convenient to use a pen. I think NPH comes in a pen, but that's more expensive.

And my feeling is that Big Pharma won't reduce insulin prices unless people stop buying their product when it costs too much.

My experience suggests that patients with no insurance and low incomes might find that they were better off with the old-fashioned bottled NPH, with regular (R) for meals if they use a bolus insulin. They're not as convenient as the newer insulins, or the pens, but no one should die because they can't afford modern insulins. Low carbohydrate intakes require less insulin, and R actually covers low-carb meals better than the faster bolus insulins.

I plan to do more experimenting with the CGM in the future. If I have any interesting results, I'll post them.

Would this "Make Diabetics Happy"?

A new invention that put little syringes loaded with insulin into capsules has riveted the popular press.

Here is one story that shows how the things work. And this story says they'll "make diabetics happy." Even the New York Times did a story on it.

As usual, the people designing new drugs and gizmos don't really understand diabetes. The biggest problem facing people with diabetes is not "painful insulin injections." It's figuring out what you can eat and, if you take insulin, how to match the insulin you inject to the food you eat.

One can also inhale insulin. But one problem with that, in addition to the problem of lung damage although the supporters of inhaled insulin say the risk is minimal, is that the amounts you  can inhale are limited. With a pen or a syringe, you can inject any amount you want, not just 4 or 8 or 12 units (the choices available with the inhaled insulin Afrezza). Would these little encapsulated syringes offer a similar benefit? I doubt it.

Another problem is that although the inventors say these things work in pigs, that's only when they have empty stomachs. One might have an empty stomach first thing in the morning, but probably not before meals, so the injections couldn't be used for bolus (premeal) insulins.

If inventors want to "make diabetics happy" they should listen to people with diabetes and see what they really want. There are probably a few people who would love to use tiny syringes in capsules, but I suspect not a lot. Inhaled insulin hasn't caught on, and I suspect encapsulated syringes would have a similar fate in the marketplace even if the cost was low.

Sure, it's fun for the scientists and engineers to come up with gizmos like this, but let's hope they come up with more useful gadgets. Continuous glucose monitors became popular when they became more affordable than some of the older CGMs. Patients are reporting major reductions in their hemoglobin A1c when they use the CGMs and find out what makes their blood glucose go up.

So I'd be happy if the engineers developed cheap CGMs that everyone could use.