What is the role of long-acting insulins in the treatment of type 2 diabetes mellitus (DM)?

Updated: Oct 23, 2019
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Answer

Long-acting insulins used in the United States include insulin glargine (Lantus, Toujeo) and insulin detemir (Levemir). Insulin glargine has no peak and produces a relatively stable level lasting more than 24 hours. In some cases, it can produce a stable basal serum insulin concentration with a single daily injection, though patients requiring lower doses typically are given twice-daily injections. Insulin detemir has a duration of action that may be substantially shorter than that of insulin glargine but longer than those of intermediate-acting insulins.

Toujeo 300 U/mL is a newer dosage strength and form of insulin glargine than Lantus 100 U/mL, having been approved by the US Food and Drug Administration (FDA) in February 2016. Compared with those of Lantus 100 U/mL, the pharmacokinetic and pharmacodynamic profiles of Toujeo are more stable and prolonged; the duration of action exceeds 24 hours. Clinical trials showed comparable glycemic control between Lantus and Toujeo, although the trials noted the need for higher daily basal insulin doses (ie, 12-17.5%) with Toujeo. The risk for nocturnal hypoglycemia was lower with Toujeo in insulin-experienced patients with type 2 diabetes, but this was not the case for insulin-naïve patients with type 1 DM or for patients with type 2 DM. [215]

With its March 2018 approval by the FDA, Toujeo Max SoloStar became the highest capacity long-acting insulin pen on the market. Toujeo Max necessitates fewer refills and, for some diabetes patients, fewer injections to deliver the required Toujeo dosage. [216]

A new ultralong-acting basal insulin, insulin degludec (Tresiba), which has a duration of action of up to beyond 42 hours, has been approved by the US Food and Drug Administration (FDA). This new basal insulin forms a soluble multihexamer after subcutaneous injection to provide a depot effect that is long lasting. It is indicated for diabetes mellitus types 1 and 2. A combination product of insulin degludec and the rapid-acting insulin aspart was also approved (Ryzodeg 70/30). Approval was based on results from the BEGIN trial [217, 218] that showed noninferiority to comparator productions. The cardiovascular outcomes trial (DEVOTE) comparing cardiovascular safety of insulin degludec to that of insulin glargine in patients with type 2 DM is ongoing. A combination product (Ryzodeg) was also approved that contains insulin degludec plus a rapid-acting insulin (insulin aspart).

A study by Zinman et al found that insulin degludec provides comparable glycemic control to insulin glargine without additional adverse effects. [219] A reduced dosing frequency may be possible because of its ultralong-action profile. Careful study is needed when making a decision regarding reduced dosing frequency.


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