New insulins present benefits, challenges
Insulin types and doses newly approved by the FDA present new opportunities and challenges for glycemic control.
The deluge of diabetes shows no signs of stopping. The disease now affects 29.1 million people in the U.S., including 8 million or so who remain undiagnosed, according to CDC statistics published in 2014. Add to this the latest CDC estimate that 86 million patients have prediabetes, and the number of diabetes cases will conceivably multiply in coming years.
“Unless we are able to get everybody exercising, following all components of the [Diabetes Prevention Program], and also eating well, these individuals will likely go on to develop actual type 2 diabetes at some point. We may be talking about 30 million now, but we're looking at 90 million later,” said Lillian Lien, MD, ACP Member, division chief of endocrinology, metabolism, and diabetes and a professor of medicine at the University of Mississippi Medical Center in Jackson.
During her session at the “Diabetes for the Internist” pre-course at Internal Medicine Meeting 2016, Dr. Lien explained how types of insulin newly approved by the FDA present new opportunities and challenges for glycemic control. (Dr. Lien disclosed that she is a consultant for insulin manufacturers Sanofi-Aventis, Merck, Eli Lilly, and Novo Nordisk.)
Insulin human injection U-500
The concentration of subcutaneous insulins is an increasingly important issue that matters more than it used to, Dr. Lien said. In the past, the only insulin syringes on the market were U-100, so clinicians often had to draw up U-500 (super-concentrated) insulin in tuberculin syringes or try to perform dose conversions, she said. “We hope this will be overcome by the recent introduction of the Humulin R U-500 KwikPen, which is live this year,” she said, although she noted that it is sometimes difficult for patients to afford. The FDA approved the U-500 short-acting insulin pen device, the first of its kind, on Jan. 21.
U-500 was not ever meant to be a standard insulin, “and then, as the obesity epidemic worsened, more and more people were placed on U-500 concentrated insulin,” Dr. Lien said. “And the reason is because we now have so many patients who have insulin resistance to a degree that they require more than 200 units of insulin daily.”
Generic insulin glargine
After much delay, generic insulins have arrived. “This has become a topic of a lot of controversy, and it is finally approaching the U.S. market,” Dr. Lien said. A generic basal insulin that is biosimilar to glargine (Lantus) was approved by the FDA on Dec. 16, 2015, and is currently associated with the brand name Basaglar. “The issue is that it is now being approved as a biosimilar insulin, which can be produced by any company, and it will therefore come under whatever name the company chooses,” Dr. Lien said. “Therefore, the KwikPen, which most of us associate with the Humalog KwikPen, is now also available as the Basaglar KwikPen.” With this generic form, simply dose as one normally would with the usual glargine (Lantus), she said.
The FDA approved insulin degludec injection (Tresiba) on Sept. 25, 2015. “That is actually an entirely new, created molecule” that forms multihexamers when injected, contributing to the subcutaneous depot's slowly delayed absorption, Dr. Lien said. The basal insulin doesn't take effect for 8 hours and lasts for up to 42 hours, which means that patients can take it every day at virtually any time, as long as doses are at least 8 hours apart, she noted. In clinical trials, this form of flexible dosing produced less nocturnal hypoglycemia than glargine, “the theory being that we may be approaching the truer basal, flat insulin,” Dr. Lien said.
Insulin degludec injection comes in a pen, in both U-100 and U-200 concentrations. “There is some excitement about the fact that the U-200 Tresiba pen is the only one that dials up to 160 units, because that means [for] all our patients who truly require over 80 units at a time, they will only need a single injection with this pen. Every other pen has a maximum single injection dose of only 80 units,” Dr. Lien said.
Insulin degludec/insulin aspart (70/30)
Also approved by the FDA on Sept. 25, 2015, insulin degludec/insulin aspart injection (Ryzodeg 70/30) is a premixed formulation with a U-100 concentration. “When you see Ryzodeg, think of it as basically a new form of 70/30,” Dr. Lien said. Adding this form to the list of other premixed insulins, 70/30 regular, 75/25 lispro, 70/30 aspart, and 50/50, may cause some confusion, she warned. “We run into this quite often: A trainee may report that the patient takes 70/30, and the question is, 70/30 what? ... No wonder our patients are also confused,” Dr. Lien said.
Insulin lispro U-200
On May 27, 2015, the FDA approved the insulin lispro (Humalog) U-200 KwikPen, which was previously only available in a U-100 concentration. Because there has been no name change, unlike with some of the other new insulins, be sure the electronic medical record (EMR) accounts for both concentrations of this rapid-acting insulin, Dr. Lien cautioned. However, “errors should be less of an issue because it is only dispensed as a pen, so they will have to simply dial the units and not worry about volume ... and that was the whole point of bringing all the new insulins out in pen form,” she said.
As Dr. Lien emphasized throughout her talk, a unit is a unit, even if the volume is less because the concentration is higher. “The issue of drawing up U-500 in incorrectly labeled syringes led to much confusion. ... The reality is, units are units. Dial it up to the number you want—that's all that matters [as long as it is dispensed from a pen],” she said.
Insulin glargine U-300
Toujeo, which was approved by the FDA on Feb. 25, 2015, is simply insulin glargine injection in a U-300 concentration, which comes in a pen. The basal insulin has a 6-hour onset and a duration of about 36 hours (compared to Lantus' 24 hours), so dosing should occur once per day at the same time each day, Dr. Lien said.
Be wary of mistakes with the new glargine, Dr. Lien said, stressing that its higher concentration does not mean clinicians should lower the dose. Specifically, when switching to Toujeo from Lantus, use the same unit-for-unit dose, she said. “From a conversion standpoint, think of it as 1:1 because any difference in bioavailability is not thought to be so clinically significant as to indicate an adjustment.”
This article was updated on July 13, 2016.