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Exploding patient numbers mean that insulin use will increase - as will varieties of insulin, methods of administration, and dosage algorithms.
As the cohort of people with diabetes continues to grow, so will the number of patients who use insulin to manage their blood glucose. It is likely that the number of insulin products, administration methods, and ways to determine the best dosage regimen for a given patient will continue to grow as well.
The basics about diabetes will not change. Treating both type 1 and type 2 diabetes depends on achieving blood glucose levels that are as close to normal as possible. In type 1 diabetes, this can be accomplished only with insulin. In type 2 diabetes, this can be achieved with oral medications, with a combination of oral medications and insulin, or with insulin alone.
Because type 2 diabetes is progressive, treatment often must change with it through those three options, with most type 2 patients eventually needing to use insulin, said Jennifer D. Smith, PharmD, BC-ADM, CDE, associate professor at Campbell University College of Pharmacy & Health Sciences and clinical pharmacist practitioner at Wilson Community Health Center in Wilson, N.C. Doses of insulin for patients with type 2 diabetes must be regularly evaluated and increased as needed, she said.
The point at which a person with type 2 diabetes should begin insulin therapy is a subject of debate and occasional confusion. In 2012, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) jointly issued a statement addressing the question.
While the statement emphasized that treatment must be tailored to the individual patient, it called for use of insulin as the initial therapy when the patient’s HbA1C level is 10% or higher. Patients whose A1C level is 9% or higher can begin using either insulin or combination therapy with two noninsulin drugs. For patients who were started on one noninsulin drug and who did not reach glycemic goals, basal insulin can be added to the initial drug after approximately three months. Insulin should be added as a third medication if therapy with two noninsulin medications does not achieve glycemic control, especially if A1C is 9% or higher.1
Once treatment with insulin is determined for a given patient, there comes the choice of which ones and in what combinations. Several types of insulin or insulin mixes are available, which means that people with diabetes and their physicians and pharmacists need to stay abreast of current practice and of the new types of insulin to come onto the market.
The most common insulin therapy for both type 1 and type 2 diabetes uses the basal-bolus strategy. The intermediate-acting and long-acting insulins are used as basal insulins, the style of insulin injection that most closely mimics the way the pancreas secretes insulin between meals. Basal insulins are usually administered in one dose a day.
Rapid-acting and short-acting insulins are used as boluses, the injections that should be administered at the start of meals.
Rapid-acting insulins (such as Humalog or NovoLog) have an onset within 15 minutes and a duration of action of between three and five hours. Short-acting insulins (Humulin or Novolin) have an onset of action of 30 to 60 minutes and a duration of action of between five and eight hours. Intermediate-acting insulins (Humulin N or Novolin N) increase the onset of action to two to four hours and the duration to between 10 and 16 hours. Long-acting insulins (Lantus or Levemir) increase onset further, to an onset of two to three hours and to a duration of 20 to 24 hours.
Then there are the premixes, which combine a long-acting insulin and a short-acting insulin in a single injection. The ratios between the two types are usually 75% longer-acting and 25% shorter-acting or 70% and 30%. The advantage with premixes is that the patient requires fewer injections per day compared to a basal-bolus regimen.
Pharmacists must know the differences between these insulin products, along with when they are appropriate to use and for whom, said Lindsay Sheehan, PharmD, CDE, a clinical pharmacy practitioner and ambulatory care clinic leader with Carolinas HealthCare System in Kannapolis, N.C.
“The majority of pharmacists have an understanding that maybe this is a mealtime insulin and that one is long-acting,” Sheehan said. “I would say the majority of pharmacists would know that. But there are going to be some who don’t.”
Sheehan noted that, when she worked in a community pharmacy several years ago, some of her pharmacist colleagues did not know the difference between a long-acting and a short-acting insulin. She now trains pharmacy students from Wingate University School of Pharmacy in North Carolina. “My students? I want to them to leave here knowing about the different insulins.”
Insulin concentrations add another wrinkle in the choice of insulin.
Patients need to understand that the concentration of the insulin they use - such as U100 or U500 - matters, Sheehan said. Patients need to be taught to look at vial labeling to ensure they are getting the right insulin and administering the right amount in each injection.
A patient who is supposed to administer a U100 insulin but who has been given a U500 insulin will be injecting a dose five times as high, she warned.
Many types of insulin concentrations are being studied now, including U200 and U300 concentrations that will come to market within a few years, Sheehan said. “It will be really confusing then,” she said. “Pharmacists are going to have to come up to speed.”
Longer-lasting insulins are in the development pipeline. One is degludec, an ultra-long-acting basal insulin, said Marissa C. Salvo, PharmD, BCACP, assistant clinical professor in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy in Storrs, Conn. Degludec has a duration of action of up to 40 hours and is approved for use in the European Union.
Administration methods are also expanding. Syringes, preloaded pens, and insulin pumps have been around long enough for most pharmacists to be familiar with them.
However, Sheehan has been working with a disposable insulin delivery device (V-Go; Valeritas), and has found that many community pharmacists are not familiar with it and confuse it with an insulin pump. (See “Insulin delivery: Disposable device ends need for repeated injections” in this issue.)
The choice of when to administer long-acting insulins each day is also seeing some changes. Patients are often instructed to take a long-acting insulin at 10 pm, noted Smith. But she has found that many older patients do not want to take it just before bedtime because they are afraid their blood sugar will drop too low while they sleep, she said.
“Now they have found that it can be given any time of the day, as long as you are consistent,” she said.
Just as there are several types of insulin available, so there are several ways to initiate insulin therapy and titrate doses. Patients are started on low doses of a long-acting basal insulin (Lantus or Levemir) and are then titrated to achieve the target fasting blood-glucose level. Various algorithms are used to titrate doses of basal insulin.
“I don’t think there is one right or wrong way to dose insulin. There are myriad ways to dose insulin,” said Jennifer Smith. “Insulin dosing is more of an art than a science right now.”
“I think pharmacists know the basics about insulin dosing,” said Smith. But as the number of people with diabetes rises, the basics about insulin dosing are changing, she added.
The Treat-to-Target Study2 evaluated a titration algorithm for a long-acting insulin (glargine) in type 2 diabetes patients. The study found that, when glargine was added to oral therapy, good A1c levels were achieved in most type 2 patients through systematic titration of the bedtime dose of basal insulin.
The Adjust-to-Target Study3 compared two titration algorithms for adjusting mealtime doses of rapid-acting insulin. The study found that basing weekly adjustments of mealtime insulin doses on blood glucose levels from the week before was as safe and effective as adjusting insulin doses to the amounts of carbohydrates consumed.
Adjusting doses to carbohydrate intake can be complex and confusing for some patients, Salvo noted. “For a patient with low health literacy, it is a complex task and may not work as well as something else.”
A third method of determining the best insulin dose is “basal plus one.”4 This involves administering an injection of a rapid-acting insulin once or twice per day at meals and has been found to work as well for most patients as three before-meal injections. “If you can take two injections rather than more each day, why not do that?” Smith said.
Pharmacists have a responsibility to address any concerns and confusion their patients with diabetes may have, whether they pertain to insulin or to other issues related to their diabetes management, said Salvo. “We want to and should be making sure that the patient is using insulin correctly.”
The best way to do this is to educate patients each time they pick up their insulin, Salvo said. Pharmacists may have more points of contact with patients than physicians do.
“It is not just sharing information, but getting the patient to participate in his or her care and work toward making changes,” she said.
Physicians too might need advice, as they determine which insulin regimen will suit a patient best, Salvo noted. “Pharmacists are abreast of the current drugs on the market; the kinetics of the drugs, the indications, and the appropriate individuals who might be candidates.”
Smith agreed. “Pharmacists have to do some doctor education. Some doctors are onboard and understand. But in general, it is education across the board for everyone.”
If patients are using insulin pens, pharmacists should occasionally ask to see how they are dialing their dosage, Smith noted. Some pens are marked only in even numbers, not odd, and patients might not be dialing odd-numbered doses correctly, she said.
In some instances, the pharmacist might learn that a patient is deliberately using less than the prescribed dose in an effort to manage cost by stretching the prescription. Or patients might need additional time with a diabetes educator if they seem unsure about how to dial the right amount on an insulin pen, fill the syringe correctly, or rotate their injection spots.
“You have to make sure that all communication is patient-centered,” Salvo said.
A patient recently told Smith that he was taking 20 units rather than the 24 that his doctor had prescribed. When she asked him to show her the dosage, he showed her that he was actually dialing the pen to 10 units. “He was trying to stretch his insulin and he was also afraid of low blood sugar,” she said.
Patients might tell their pharmacists what they think the pharmacists want to hear, the same way they do with their physicians, Smith said. Pharmacists might need to conduct some motivational interviewing and learn each patient’s concerns.
1. Inzucchi SE, Bergenstal RM, Buse JB, et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: A patient-centered approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diab Care. 2012; 35:1364–1379.
2. Riddle MC, Rosenstock J, Gerich J; Insulin Glargine 4002 Study Investigators. The treat-to-target trial: Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003; 26:3080–3086.
3. Bergenstal RM, Johnson M, Powers MA, et al. Adjust to target in type 2 diabetes: Comparison of a simple algorithm with carbohydrate counting for adjustment of mealtime insulin glulisine. Diabetes Care. 2008;31:1305–1310.
4. Davidson MB, Raskin P, Tanenberg RJ, et al. A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure. Endocr Pract. 2011;17:395–403.
Valerie DeBenedetteis a medical news writer in Putnam County, N.Y.