Q&A: What to know about ultra-long-acting insulins
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Susan Weiner, MS, RDN, CDN, CDCES, FADCES, talks with Katelyn O’Brien, PharmD, BCPS, CDCES, BC-ADM, about situations in which an ultra-long-acting insulin may be a good choice.
Weiner: More than 7.4 million people with diabetes use insulin. With so many options for insulin therapies, how do you decide which is the best insulin for an individual?
O’Brien: An initial response is to consider the individual’s insurance formulary. However, when an insurance plan covers more than one basal insulin option, it is important to know the differences between products. For example, insulin detemir (Levemir, Novo Nordisk), which is set to be phased out in 2024, has a more pronounced peak than other basal insulins and in some cases requires twice-daily dosing due to variable durations of action.
Another difference is in device availability and the person’s preference. Many people using multiple daily injections prefer to use insulin pens. There are small differences in pen design. For example, the FlexTouch pen (Novo Nordisk) has a non-extending dose button, whereas KwikPen (Eli Lilly) and SoloStar (Sanofi) pens do extend. Considerations around insulin dose and dexterity can be factored into selection of basal insulin based on ease of use with the non-extending pen design. The FlexTouch also offers an end-of-dose click, which can provide an extra layer of confidence that the dose has been administered.
Weiner: You mentioned the duration of action of Levemir, what are the benefits of some of these newer ultra-long-acting insulins?
O’Brien: Understanding insulin pharmacokinetics can help a clinician or diabetes care and education specialist to recommend a specific insulin for a person with diabetes. Insulin degludec (Tresiba, Novo Nordisk) is available as U100 and U200 concentrated insulin. U100 degludec is available in a pen or in a vial, and U200 degludec is available in a pen only, with doses available in 2 U increments. Insulin glargine U300 (Toujeo, Sanofi) is available in two types of pens.
U300 insulin glargine has a duration of action of 36 hours, and insulin degludec has a duration of action of 42 hours, compared with U100 insulin glargine’s duration of 24 hours. This longer duration is why these two agents are considered ultra-long acting.
Insulin degludec is unique in that prior to injection, degludec exists in dihexamers in the presence of zinc and phenol. Once injected, the phenol diffuses and the degludec dihexamers assemble and form multihexamer chains. These chains are too large to cross into the blood and therefore create an insulin depot. As zinc diffuses, insulin monomers are slowly released from the ends of the multihexamer depot chain and are continuously absorbed into circulation. This allows a flexible dosing schedule and a longer duration of action.
A person can inject insulin degludec at any time of day so long as there has been 8 hours since the last dose. With the depot, and as long as there are 8 hours between doses, there is not concern for insulin stacking. I prefer insulin degludec for individuals with variable work schedules or inconsistencies in their day. This allows for improved use and prevents hyperglycemia with missed basal doses or hypoglycemia when dosing basal insulins too close together.
Speaking of hypoglycemia, when studied in the SWITCH 2 trial, insulin degludec was associated with a decreased rate of overall symptomatic hypoglycemia compared with U100 insulin glargine among patients with type 2 diabetes. In the EDITION 3 and EDITION 4 trials of U300 vs U100 glargine in type 1 and type 2 diabetes populations, respectively, U300 was noninferior with regard to change in HbA1c. Secondary endpoints showed lower risk for hypoglycemia with U300. In trials comparing insulin degludec with U300 glargine, among both people with type 1 and type 2 diabetes, trials demonstrated noninferiority with similar rates of hypoglycemia.
Weiner: What about someone who is already on a basal insulin, what are some scenarios where a person might consider switching to an ultra-long-acting basal insulin?
O’Brien: Both of the ultra-long-acting basal insulins are available as concentrated formulations. This can benefit individuals who require higher insulin doses to improve absorption, as the same amount of insulin is being injected in a smaller volume.
So, for example, if an individual is on insulin glargine 80 U and needs the dose to be increased, the package insert would recommend splitting the dose into two injections. This would be a perfect scenario to switch the person to U300 glargine or U200 degludec.
Another situation I encounter is people with inconsistent or variable schedules due to work, school, sleep patterns, etc. They often are unable to inject their basal insulin at the same time every day. Similarly, an older adult with diabetes may have a caregiver with a variable schedule. These are two examples in which I would specifically suggest switching to insulin degludec given the flexible dosing schedule compared with insulin glargine, which must be injected at the same time every day.
Weiner: Are these ultra-long-acting insulins more expensive?
O’Brien: As mentioned earlier, the selection of insulin therapies may depend on insurance formularies. In 2023, Medicare announced an insulin price cap. The cost of a 1-month supply of each Part D and Part B covered insulin is capped at $35, and insured parties do not have to pay a deductible for insulin.
In addition to Medicare, in 2023, three major insulin manufacturers lowered the prices of insulin to help improve access to necessary treatment options. Most Medicaid enrollees receive insulin for free or at a significantly reduced cost. However, each state makes its own determination about which diabetes medications and supplies are covered through its Medicaid program.
For more information about what medications and supplies are covered in a specific state, please contact the state Medicaid agency. For uninsured people, it would be best to seek out prescription assistance programs with the insulin manufacturers to see if they qualify. For commercially insured people, half of the states and Washington, D.C., have signed insulin copay caps into legislation, more information can be found here: https://diabetes.org/tools-resources/affordable-insulin/state-insulin-copay-caps.
References:
- Battelino T, et al. Diabetes Ther. 2020;doi:10.1007/s13300-020-00781-6.
- Bolli GB, et al. Diabetes Obes Metab. 2015;doi:10.1111/dom.12438.
- Home PD, et al. Diabetes Care. 2015;doi:10.2337/dc15-0249.
- Rosenstock J, et al. Diabetes Care. 2018;doi:10.2337/dc18-0559.
- Saydah SH. Medication use and self-care practices in persons with diabetes. In: Cowie CC, et al, eds. Diabetes in America, 3rd ed. Bethesda, Md: National Institutes of Health; 2017 (NIH publ. no. 17-1468).
- Wysham C, et al. JAMA. 2017;doi:10.1001/jama.2017.7117.
For more information:
Katelyn O’Brien, PharmD, BCPS, CDCES, BC-ADM, is a clinical pharmacy specialist and certified diabetes care and education specialist at Boston Medical Center. She can be reached at katelyn.o’brien@bmc.org address; X (Twitter): @KOBPharmD.
Susan Weiner, MS, RDN, CDN, CDCES, FADCES, is co-author of The Complete Diabetes Organizer and Diabetes: 365 Tips for Living Well. She is the owner of Susan Weiner Nutrition PLLC and is the Endocrine Today Diabetes in Real Life column editor. She can be reached at susan@susanweinernutrition.com; X (Twitter): @susangweiner.
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