Jay H. Shubrook, DO; Clipper F. Young, PharmD, MPH, CDE


June 05, 2017

Jay H. Shubrook, DO: Hi. This is Jay Shubrook, DO, family physician and diabetologist at Touro University of California. Today, we continue our series on practical insulin use in primary care. One of my colleagues, Clipper Young, PharmD, and a certified diabetes educator and MPH, is here with us. He works exclusively in a diabetes service for his clinical practice. Welcome, Dr Young.

Clipper F. Young, PharmD, MPH, CDE: Thank you for having me here, Jay.

Complexities of Basal-Plus Therapy

Dr Shubrook: Today, we are going to talk about the complexities of "basal-plus." When I use insulin, I typically start a patient on basal insulin; if more is needed, I would then go to insulin at all meals. We would call that "basal-bolus" insulin. But now there are so many choices. I would like to hear your thoughts about this. Let's discuss a population that started basal insulin and got to the right dose. What do we do after basal insulin?

Dr Young: There are several options. We can do basal plus one dose [of insulin] before the biggest meal, or we can do basal plus three, meaning [one dose before] three meals. According to the 2017 American Diabetes Association guidelines,[1] there are different ways to start the initial dose [of insulin]. We can start with 4 U, or 0.1 U/kg, or 10% of the basal dose. A newer class of medications, glucagon-like peptide-1 (GLP-1) receptor agonists, is another alternative that can also be added to basal insulin.

Dr Shubrook: You have mentioned many options, which make me a little nervous and confused. That is part of the problem—there are so many choices. Let's talk about basal plus one [dose of] insulin. For the insulin at one meal, we can choose a fixed dose of 4 U or a weight-based dose of 0.1 U/kg. What kinds of insulins can we use for basal plus one?

Dr Young: Two subclasses of insulin are available: rapid insulin and short-acting insulin. For rapid-acting insulin, there are three options: aspart (NovoLog®), lispro (Humalog®), or glulisine (Apidra®). Regular insulin is a subclass as well.

Dr Shubrook: All of those could be used as a mealtime insulin?

Dr Young: Correct.

Dr Shubrook: How do they differ in terms of timing?

Dr Young: We usually instruct patients to inject rapid-acting insulin 15 minutes before their meal. If they choose to use regular insulin, we instruct them to use it 30 minutes before their meal.

Dr Shubrook: So it is important to know the time of insulin administration in terms of dosing with your meal.

Dr Young: Correct, that is very important.

Dr Shubrook: I had always thought that if you need insulin, you need it for your food. And if you are like me, I eat more than three meals a day. How could covering one meal a day with insulin be adequate?

Dr Young: Studies[2] have shown that adding one dose of rapid insulin (mealtime insulin) is as effective as adding three doses. The reason being: Some patients might not take all three doses even though they have been instructed to do so. Usually, when we add the one dose of mealtime insulin, we do it before the biggest meal.

Nuances of Administration and Avoiding Hypoglycemia

Dr Shubrook: That was really hard for me to get comfortable with as a guy who always replaced all of the meals. You brought up two really important things. One is: Patients struggle with adherence. Doing anything three or more times a day is hard, and we do not always get it right. Number two, heaven forbid we forget the biggest meal of the day. If we have to be adherent, let's at least be adherent with the meal containing the most carbs.

On the flip side, patients were taking doses of insulin for something that is not a real meal, like a cup of coffee, and then they are at risk for higher rates of hypoglycemia. What I heard is that the basal-plus-one algorithm is as good as basal plus bolus, with less hypoglycemia. What a game changer. Would you use the same dose for basal plus one as you would for basal-bolus?

Dr Young: Initially, we would use the same dose because the guidelines[1] recommend that when we use one dose or three doses, we start at the same dose. The only difference would be the frequency of injection because we would assume that they would eat about the same amount of food. Starting with different amounts will lead to a higher chance of hypoglycemia.

Dr Shubrook: That is an important concept. If we are going to use insulin at a mealtime, we need to instruct the patient to have relatively similar sized amount of carbs per meal. Do you ever use the "big meal/small meal" dose of insulin?

Dr Young: We can, but usually for type 1 patients. The specifics of carbohydrate content are even more important for people with type 1 diabetes.

Dr Shubrook: Stick with that fixed dose; take it before the meal. You mentioned GLP-1 receptor agonists as an alternative to meal-time insulin. After basal insulin, how do I decide whether to go with insulin or GLP-1 receptor agonist? What is the risk/benefit profile? The benefits and the disadvantages?

Advantages and Disadvantages of GLP-1 Receptor Agonists

Dr Young: That is a very good question. GLP-1 receptor agonists are glucose dependent, meaning that they work better when [blood] sugar is higher but do not work as well when sugar is slowly going down. The advantage is that they significantly reduce the hypoglycemia risk by being a glucose-dependent medication. In terms of dosing, there are three once-weekly GLP-1 receptor agonists out there, and patients love them.

Dr Shubrook: The GLP-1 receptor agonist has the advantages of less injections and less hypoglycemia. I would also add weight loss as a potential advantage. What are the disadvantages?

Dr Young: There are a few studies[3,4] stating that some patients might develop pancreatitis. There is a black box warning about the risk for a very rare medullary thyroid cancer.[5] That is always something that we have to [discuss] before we start GLP-1 receptor agonists.

Dr Shubrook: Because a GLP-1 receptor agonist is not insulin, it has different side effects. You mentioned the association with pancreatitis, which I think is really an idiosyncratic reaction, and the black box warning for medullary thyroid cancer. I would also add the gastrointestinal side effects that come along with GLP-1 receptor agonists that are not seen in insulin. What are those, and how often do you see those?

Dr Young: Gastrointestinal side effects such as nausea, vomiting, and diarrhea can happen, but it does not happen that often. If it does happen, it usually goes away after a few weeks once the patient gets more used to the medication.

Dr Shubrook: Do you ever give specific patient instructions about how to eat when taking a GLP-1 receptor agonist?

Dr Young: We always tell the patient that if they feel full, they should not force themselves to eat. If they pass that point, they might throw up. Actually, that is an advantage of the medication—patients will get full easily, so they will not keep eating.

Dr Shubrook: The incretin effect of the GLP-1 receptor agonist brings back the feelings of satiety, which many people with type 2 diabetes do not have. Bringing that back is a good thing, and it can contribute to weight loss. Listening to our bodies can be a challenge but is very important.

Final Thoughts: Intensive Glucose Monitoring

Dr Shubrook: You shared some really important things today. You said that after basal insulin, we could use basal-bolus insulin therapy. In type 2 diabetes, basal plus one is as good as basal-bolus. We could also use basal plus an incretin [agent]. The good news is: There are lots of choices from which a primary care provider can choose. The challenge is, of course, that there are more medications we need to know better. Are there any other things you would like to share with our listeners today?

Dr Young: Patients take these medications, but many of them do not really check their sugars. We stress the importance of adding medications, but we also need to know the patient's sugar levels. One technique commonly used is the seven-point glucose monitoring technique.[6] Patients check their sugar before and after each meal and before bedtime. However, they do not have to do it every day. Doing so maybe 3 days to 7 days before their next appointment will give us a very comfortable picture of their sugar levels.

Dr Shubrook: Intensive glucose monitoring just before the appointment gives the provider great information about current medications and how they are working.

Dr Young: Correct.

Dr Shubrook: I do not know about you, but I always behave a little bit better before I go to my doctor. I wonder if diet changes as well. The seven-point monitor is a great point, but I also know we have to make sure we match their real lives.

Thank you so much for your insight today and for participating.


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