Diabetes Care: Optimal Dosing With Humulin R U-500

Robert Hood, MD: Before the initiation and titration trial, I personally put people on a TID all the time. I thought TID was better than BID. If you’re going to buy the insulin, why not give it 3 times a day? One of the really fun things about the trial is that it completely proved me wrong. BID worked just as well as TID. Now, that doesn’t mean that you have to start with BID: It’s up to you as a clinician. BID had the same A1C reduction. With measures of compliance and disease-state burden and injection discomfort, some of the results were actually better with BID than TID. So, I start out with BID with most of my patients. We split to 60% in the morning and 40% in the evening. Remember to do your 20% dose reduction if their A1C [glycated hemoglobin] is 8% or lower. If you opt to go for the TID dose, give 40% in the morning, 30% at lunchtime, and 30% with the evening meal. That total dose may be reduced by 20%, then split according to those ratios, and then you can titrate the insulin afterward.

It was heartening that at the end of the trial, the ratio of insulin between the different injections was very similar to what we used at the time of initiation. That does validate that these are reasonable starting points. An individual patient may vary quite a bit at the end of a study period, but on average, that’s thought to be a good way of splitting up the insulin.

Patients should be encouraged to check their sugar 4 times a day. If the dose is increased, we also recommend doing a reading at 3 o’clock in the morning to make sure they’re not getting nocturnal hypoglycemia. If you’re adjusting a 3-day injection protocol, you’re going to be adjusting your breakfast insulin based on the lunchtime blood sugar, the lunchtime insulin based on the evening blood sugar, and then the evening dose based on the breakfast blood sugar the next day. That being said, if you had hypoglycemia at 3 o’clock in the morning or at bedtime, that evening dose will be reduced even if the morning blood sugar was high. If you’re adjusting a twice-a-day regimen, you’re going to adjust the evening dose just like you did with TID, but the breakfast dose will be adjusted based on the evening meal blood sugar. It’s somewhat analogous to what happened with TID. If you are low at lunchtime, that’s going to call for a dose reduction even if you’re high at the evening meal.

We looked at the median blood sugar for the previous 3 days and used that to adjust the therapy. The target blood sugar, which was taken from the American Diabetes Association (ADA) guidelines at the time, was from 71 mg/dL to 130 mg/dL. If they were 70 mg/dL or lower, there was a 10% reduction in the dose of insulin. If it was 131 mg/dL to 180 mg/dL, there was a 5% increase; if 181 mg/dL to 220 mg/dL, there was a 10% increase; if above 220 mg/dL, there was a 15% increase. We used a percent change of insulin because these patients are on widely varied doses of insulin. They’re on at least 200 units, but some patients could be on as much as 600 units. So, it makes a lot more sense to use a percent change than an absolute change.

Serge Jabbour, MD: When I start U-500, I pick the dose initially based on what the A1C level is and convert those patients from the U-100 to just U-500. I tell patients to take it 30 minutes before their meal. I use it twice a day only. In the study, they compared twice-a-day versus 3-times-a-day dosing, and they both had the same A1C reduction. I tell patients that in the initial few months, they may gain a little weight. That’s always a cost to pay for doing well on insulin, and that’s typical of all insulins. When you start insulin and your sugars come down, you may gain some weight, but that will stabilize over time. In those patients on U-500, it’s unlikely to see severe hypoglycemic events because they have such a severe insulin resistance to start with. But of course, when their sugars start to come down and their A1C gets better, that’s when we might see more hypoglycemic events. The key is to take that insulin 30 minutes before they eat. That’s one way we could prevent hypoglycemia, and of course we tell patients to eat 3 meals a day and have a small snack at bedtime, like with any patients on insulin. We also give them tips on how to prevent hypoglycemia if they are active, if they are not sick or not eating. Of course, we tell them to call us any time if they’re not sure what to do, and if they become hypoglycemic, we tell them how to treat it correctly.

Robert Hood, MD: The U-500 pen is just as available as the vials are. Because it’s so much safer and easier for patient compliance, I would urge you to use the U-500 pen. But be careful. The vial or the pen may not always be in the pharmacy. A good way of starting with the patient is taking that into consideration. If you’re not sure if your pharmacy carries it, the patient needs to be aware of that. Don’t let them go there thinking they’re going to get their first injection tonight if the insulin’s not available to them.

Another issue about pens is that there are patients out there who have visual and motor issues, and that makes it difficult to give the vial and syringe. So, if you’re considering a vial and syringe with any insulin therapy in a patient, make sure the patient can draw that insulin and give it accurately. It’s funny to think that in a hospital ward, we have 2 registered nurses looking carefully at an insulin dose given with a syringe, but we send Mrs. Smith home—who’s 80 years old and half blind with arthritis and a prescription for a vial and syringe—and assume that she’s going to do it properly.

Davida F. Kruger, MSN, APN-BC, BC-ADM: In endocrine practice, we’ve been using U-500 my entire career, which is as long as it has been on the market. I’m feeling very comfortable with it. But the confusion has always been in the dosing. We’ve had to either use a U-100 syringe and do a lot of mathematic conversions, or use a TB syringe. The concern always comes when the patient gets admitted to the hospital or someone else is managing their care: Are they going to do the math the same and write the prescriptions to make sure they get the right amount of insulin?

Now that we have both a dedicated pen and a dedicated syringe, you write the dose, the patient takes the dose, and it couldn’t be easier. The patient can get the benefit of using this concentrated U-500 insulin. For the health care provider, the comfort level of dosing is much easier, and the conversation between the health care provider and the patient, the pharmacist, the hospital, or anywhere the patient’s going to be with a dedicated syringe and/or a dedicated pen makes life so much easier to use this insulin.

Transcript edited for clarity.