How to Safely Stop Tresiba (Insulin Degludec): A Clinical Discontinuation Protocol

Is there a discontinuation protocol for Tresiba?

The Tresiba label contains no taper or stopping schedule. Its dosing section covers starting doses, increasing the dose no more often than every 3 to 4 days, missed doses, and how to move a patient onto Tresiba from another long- or intermediate-acting insulin [1]. The closest thing to discontinuation guidance is a general rule that applies to any regimen change: changes in insulin strength, manufacturer, type, injection site or method of administration can affect glycemic control and predispose to hypoglycemia or hyperglycemia, and the label calls for close medical supervision with more frequent blood glucose monitoring [1].

The label does not provide a dose-reduction step, an interval between reductions, or a threshold for reversing a reduction [1].

How long degludec keeps working after the last injection

At steady state, degludec peaks at a median of about 9 hours and has a half-life of roughly 25 hours. Its glucose-lowering effect lasted at least 42 hours after the last of eight daily injections, with peak effect at a median of 12 hours [1]. Steady state takes 3 to 4 days to reach, and day-to-day variability in total effect was 20% [1].

The label also notes that the long-acting effect of Tresiba may delay recovery from hypoglycemia compared with shorter-acting insulins [1].

A missed dose is not the same as stopping

The label's instruction for a missed dose in adults is to inject the daily dose during waking hours when the miss is noticed, keeping at least 8 hours between consecutive injections [1]. For children who miss a dose, the label says to contact a healthcare provider for guidance and to monitor blood glucose more frequently until the next scheduled dose [1]. Those instructions assume the next dose is coming.

Type 1 diabetes: basal insulin is one half of a two-part regimen

Tresiba is indicated to improve glycemic control in patients 1 year of age and older with diabetes, and the label states that in type 1 diabetes it must be used together with a short-acting insulin [1]. It is not recommended for the treatment of diabetic ketoacidosis [1]. The label's dose-conversion instructions run in one direction only, for patients starting Tresiba: adults start at the same unit dose as their previous long- or intermediate-acting insulin, and children 1 year and older start at 80% of that dose [1].

Other factors the label lists that change insulin needs

The label says dose adjustments may be needed with changes in physical activity, meal patterns, renal or hepatic function, or during acute illness, to minimize the risk of hypoglycemia or hyperglycemia [1]. Its interaction table lists GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors and other antidiabetic agents, ACE inhibitors, angiotensin II receptor blockers, fibrates, fluoxetine, monoamine oxidase inhibitors, salicylates and sulfonamide antibiotics as able to increase hypoglycemia risk. Corticosteroids, diuretics, estrogens, oral contraceptives, atypical antipsychotics, protease inhibitors and thyroid hormones can blunt the glucose-lowering effect [1]. Pioglitazone and other thiazolidinediones taken with insulin can cause dose-related fluid retention that may cause or worsen heart failure [1].

A labeled switch involving insulin degludec

Xultophy 100/3.6 is a different medicine: a fixed combination of insulin degludec and liraglutide for adults with type 2 diabetes [2]. The Xultophy 100/3.6 label says to discontinue basal insulin or a GLP-1 receptor agonist before starting Xultophy. It sets the starting dose at 16 units once daily for patients already using basal insulin or a GLP-1 receptor agonist, and at 10 units once daily for patients naive to both [2]. That is a labeled replacement of basal insulin with a combination product, not a withdrawal to no insulin.

What the label flags about hypoglycemia

Hypoglycemia is the most common adverse reaction of Tresiba and can be life-threatening [1]. The label notes that risk generally increases with the intensity of glycemic control, and lists renal or hepatic impairment, changes in meal patterns or activity, and interacting drugs among the factors that can raise it. Awareness of hypoglycemia may be reduced in people with longstanding diabetes, diabetic neuropathy, or beta-blocker use [1]. Tresiba is contraindicated during an episode of hypoglycemia [1].