When May the Newer Insulins Be Appropriate for Patients?

Kim A. Carmichael, MD, FACP
Volume 55 - Issue 10 - October 2015

Q. What patients may need the newer insulins?

A. Although traditional insulins provide many options for treating patients with diabetes, some individuals require very high daily doses involving multiple shots that may cause local skin discomfort and reduced compliance. Others have aversion to needles and may be unable or unwilling to take insulin with meals or to correct high glucoses. Some of the pharmacokinetics of the newer insulins as well as a new insulin delivery device may also provide particular benefits for basal or mealtime control.

Q. What new basal insulin are available for use?

A. One new basal insulin (Toujeo, Sanofi) is a concentrated form of glargine, an already existing insulin that is widely used. This U-300 glargine has 300 units per mL, instead of its U-100 counterpart (Lantus, Sanofi) which has 100 units per mL, and is available in a pen that holds 450 units versus up to 300 units in the traditional pen. The injections of high doses of insulin in this formulation require much less volume, which provides the potential for better patient comfort. 

In addition, the pharmacodynamics are somewhat different with U-300 versus U-100 products with glargine or detemir (Levemir, Novo Nordisk). U-300 glargine starts working in 2 to 4 hours, has no peak onset of action, and has a median duration of about 30 hours.1 This makes once-daily administration ideal for many patients. In contrast, U-100 glargine has an onset in 2 to 4 hours, has no major peak, but only lasts 20 to 24 hours. Furthermore, up to 57% of patients require twice-daily administration.2 Insulin detemir has an onset in 1 to 3 hours, peaks in 6 to 8 hours, and lasts 18 to 20 hours,2 but also often requires shots twice daily.

Insulin degludec (Tresiba, Novo Nordisk) was approved by the FDA in September 2015.3 This is a U-100 with a flat, stable profile, a half-life of 25 hours, and lasts approximately 42 hours.4 This may be given once daily at any time of day.

Q. What new mealtime insulin injection is available for  patients?

A. Insulin lispro is now available in a U-200 form, in addition to the U-100 product (Humalog, Eli Lilly and Company) which has been on the market for many years. This U-200 insulin is available only in a pen format, provides insulin in one-half the volume of its U-100 counterpart, and contains 600 units per pen instead of the usual 300 units. This allows the convenience of using fewer pens, particularly for those who need large doses of short-acting insulin. The pharmacodynamics of U-200 insulin is similar to U-100 and requires no additional dose adjustment during transition.5

Q. What other option is available for persons for mealtime insulin?

A. Technosphere insulin (Afrezza, Sanofi) is now available for inhalation, ideally suited for mealtime administration. It comes in 4- and 8-unit cartridges and has an onset in 12 to 15 minutes and lasts up to 180 minutes.6 In a recent clinical trial, this was found to be noninferior to subcutaneous insulin aspart (Novolog, Novo Nordisk) in combination with basal insulin in persons with type 1 diabetes.7 This insulin resulted in fewer episodes of hypoglycemia, less weight gain, but a greater incidence of cough.

Inhaled insulin should not be used in persons who smoke or who have recently stopped smoking. There is a boxed warning from the FDA to avoid using inhaled insulin in persons with chronic lung disease, as it can cause acute bronchospasm. Pulmonary function studies should be performed at baseline, after 6 months of therapy, and yearly thereafter.6

Q. Are there any other new devices to provide insulin?

A. There is an FDA-approved disposable subcutaneous insulin delivery device for use in persons with type 1 or type 2 diabetes.8 The device is marketed under the name V-Go (Valeritas, Inc) and provides continuous delivery of any brand of insulin via a 30-gauge needle during a 24-hour period, providing basal fixed dose short-acting insulin of 20, 30, or 40 units. It can also deliver mealtime or correction dose insulin boluses in 2-unit increments for up to an additional 36 units per day. The device is small, lightweight, and adheres to the skin. It is generally well-tolerated, but may cause local skin irritation.

Newer insulins and the disposable subcutaneous insulin delivery device all provide particular benefits for select patients with either type 1 or type 2 diabetes. Clinicians should use clinical judgment in determining which patients are suitable for these, keeping in mind the increased costs and limited availability based on third-party coverage.

Dr Carmichael discloses that he is on the speaker’s bureaus for Merck and Janssen that may be relevant to the content of this manuscript. 

Kim A. Carmichael, MD, is an associate professor of medicine in the department of internal medicine in the division of endocrinology, diabetes, and lipid research at Washington University. 

 

References:

  1. Becker RH, Dahmen R, Bergmann K, et al. New insulin glargine 300 units mL provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 units mL. Diab Care. 2015;38(4):637-643.
  2. Wallia A, Molitch ME. Insulin therapy for type 2 diabetes mellitus. JAMA. 2014;311(22):2315-2325.
  3. FDA, FDA approves two new drug treatments for diabetes mellitus [press release]. September 25, 2015. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm464321.htm. Accessed September 29, 2015.
  4. Rodbard HW, Cariou B, Zinman B,  et al. Comparison of insulin degludec with insulin glargine in insulin-naïve sujbets with type 2 diabetes: a 2-year randomized, treat-to-target trial. Diabet Med. 2013;30(11):1298-1304.
  5. Humalog [package insert]. Indianapolis, IN: Eli Lilly & Co;2015.
  6. Afrezza [package insert]. Bridgewater, NJ. Sanofi-Aventis, US, LLC;2002-2015.
  7. Bode BW, McGill JB, Larber DL, et al. Inhaled technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care. 2015. 
  8. Knutsen PG, Voelker CQ, Nikkel CC. Clinical insights into a new, disposable insulin delivery device. Diabetes Spectr. 2015 28:209-213.