As the prices of newer insulin formulations have soared, there may be a role for older formulations for patients who struggle with the cost. However, patients need education on how to safely and effectively use these cheaper options.
The price of insulin has soared to such levels that it could be costing lives. Consider the case of type 1 diabetes patient Alec Smith, who turned 26, aged off of his mother’s health insurance policy last year, and was unable to afford his own policy. On his first visit to his pharmacy after his insurance lapsed, he was told his monthly diabetes supplies would cost $1,300, an expense he needed to put off until payday a few days later. He apparently tried rationing his insulin, but in a matter of days was found dead in his apartment.
His mother, Nicole Smith-Holt, related his story at an August 21 hearing in Washington, D.C., convened by Senate Democrats to look at the impact of rising prices for prescription drugs.
A recent study by Yale University researchers found that one in four patients at a New Haven, Conn., clinic had cut back on the use of insulin because of cost. A study in JAMA reported a threefold increase in the cost of insulin between 2002 and 2013, and National Public Radio reports the costs doubled again since 2012. The increases have been for the newer, analog insulin formulations, which has brought attention to the possible use of older insulin formulations for patients who can’t afford the skyrocketing costs.
A Hot Topic
That question spurred the American Diabetes Association to hold a session at its June meeting on “Insulin Therapy—To the Future and Back” that considered this question. Regular insulin and neutral protamine Hagedorn (NPH) insulin cost $24 a vial, whereas the newer analogs such as U200 lispro and U300 glargine cost $280 to $290 a vial, according to meeting speaker Dace Trence, MD, professor of medicine and director of the Diabetes Care Center at the University of Washington in Seattle.
“This topic is getting a lot of attention,” Trence tells Endocrine News, but clinicians need to remember that the newer formulations replaced the older ones “for one major reason, and that was decreasing hypoglycemia risk.”
Wendy Lane, MD, a diabetes specialist at the Mountain Diabetes and Endocrine Center in Asheville, N.C., says she remembers when Lantus (glargine), the first FDA-approved long-acting, basal, recombinant human insulin analog, was approved in 2000: “I was a physician at a camp for kids with type 1 diabetes, and for the first time in history in that diabetes camp, everybody slept through the night because the kids weren’t having hypoglycemic events at night from using NPH.”
Trence and Lane both said that they have been practicing long enough to remember when the older insulins were the only formulations available, and therefore remember why the newer ones replaced them. Lane has not prescribed the older formulations for several years because the newer ones are better.
“It’s the cost that is driving the whole picture. If cost wasn’t an issue, we would not be having this conversation. … But a lot more teaching has to be done explaining how to use them.” – Dace Trence, MD, professor of medicine and director of the Diabetes Care Center, University of Washington, Seattle
The newer formulations have been around for 15 years or more, and that time frame creates a barrier to the use of the older ones because younger endocrinologists have never seen or used NPH or regular insulin.
Limitations of Older Formulations
To go back to using the older insulins, one needs to be aware of their limitations, and more teaching of both clinicians and patients is necessary, Trence says: “If you are looking at the older insulins, there has to be an understanding that a patient’s lifestyle has to be more regimented. The peaks of these insulins and their actions require that patients not skip meals and ingest close to the same amount of carbohydrates at each meal consistently at the same time each day. Otherwise they are in trouble. The insulin is going to be in the system for quite some time, so there has to be that regimentation with regard to timing of meals as well as the amount of carbohydrate.”
The newer formulations are more consistent and predictable in their activity, while the older formulations are of longer-acting and don’t match peak effects of food as well.
Higher Insulin Needs
Trence says that one category of patients who could do well on U500 regular human insulin are those who have high insulin needs — such as more than 200 units per day. Patients with high insulin requirements may do better on U500 because of the lower volume of insulin and because it can often avoid the need for multiple injections a day — a higher number of injections reduces adherence. Trence adds that the long-acting NPH insulin “has both a basal as well as a bolus effect. So you are not using the insulin for just one purpose, you are really getting two benefits from it.”
She notes that there are also some “very specialized patient populations” who might do better on NPH, such as patients receiving high-or-medium-dose steroids or parenteral nutrition, but “usually these are hospitalized patients, so they will not be walking into your office.”
In the Literature
Trence and Lane both note that articles have begun appearing in the literature trying to justify the use of older formulations based on efficacy, but do not find the data convincing. For example, an article in JAMA in July used data from Kaiser Permanente of Northern California to compare results from patients with type 2 diabetes who began therapy with a basal insulin analog versus NPH insulin. The researchers concluded that “initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related emergency department visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.”
“It should be intuitively obvious to any practitioner why the standard of care has become the new analog insulins. We don’t have to rehash old data.” – Wendy Lane, MD, diabetes specialist, Mountain Diabetes and Endocrine Center, Asheville, N.C.
But Trence notes that using that article’s own data, “If you look closely over time, you can begin to see marked differences in terms of glycemia between the two populations. This same research group reported in JAMA earlier this year that measuring just ER and hospitalization data does not give the full picture of hypoglycemia incidence — for example, medical records captured only about one in 20 of the hypoglycemic events Kaiser Permanente Northern California members reported in a survey conducted by the Diabetes Study of Northern California.”
Lane says that as she read the article, she made a list of its shortcomings, which she was “relieved” to see an accompanying editorial: “It should be intuitively obvious to any practitioner why the standard of care has become the new analog insulins. We don’t have to rehash old data.”
Trence agrees: “It’s the cost that is driving the whole picture. If cost wasn’t an issue, we would not be having this conversation.” If patients cannot afford their analog insulin, older formulations are better than no insulin at all, “but a lot more teaching has to be done explaining how to use them.”
–Seaborg is a freelance writer based in Charlottesville, Va. He wrote about Medicare approving some CGMs for coverage in the September issue.