New Drug Review 2016

Jack DeRuiter, PhD; Pamela L. Holston, RPh, BS, BA; Taylor Joseph DeRuiter, PharmD


US Pharmacist. 2016;41(10):30-36. 

In This Article

Insulin Degludec (Tresiba, Novo Nordisk)

Indication and Clinical Profile[1,2]

Insulin degludec is a long-acting insulin analogue indicated for improving glycemic control in adults with type 1 or type 2 diabetes (T1D, T2D). The CDC estimates that 29 million people in the United States have been diagnosed with diabetes. Over time, diabetes increases the risk of serious health complications, including heart disease, blindness, neuropathies, and nephropathy. Improvement in blood-sugar control can reduce the risk of some of these long-term complications. Long-acting insulins play an essential role in the treatment of patients with T1D and in T2D patients with advanced disease.

The efficacy and safety of insulin degludec for the treatment of patients with T1D and T2D were evaluated in several controlled trials. Insulin degludec was studied as an alternative to insulin glargine as part of a basal-bolus regimen in the BEGIN Basal-Bolus Type 1 trial, which included 629 patients with T1D. Patients were randomized in a 3:1 ratio to either insulin degludec (n = 472) or insulin glargine (n = 157) plus mealtime insulin aspart. Patients in the degludec treatment arm were switched from basal insulin to insulin degludec in a 1:1 ratio, with a 20% to 30% dose reduction in patients receiving multiple basal doses per day. After 52 weeks, the reduction in HbA1c patients treated with insulin degludec was similar to that in patients treated with insulin glargine (0.40% vs. 0.39%), meeting the criteria for noninferiority. However, rates of nocturnal hypoglycemia were 27% lower in patients receiving insulin degludec versus insulin glargine (3.91% vs. 5.22%; P = .024).

In the BEGIN Basal-Bolus Type 2 trial, insulin degludec was studied as an alternative to insulin glargine in 1,006 patients with T2D. Patients were randomized to receive either insulin degludec or insulin glargine plus mealtime insulin aspart, metformin, and/or pioglitazone. Patients had an average HbA1c of 8.3% to 8.4%, and 50% of them were on a regimen of basalbolus insulin and oral antidiabetic medications. After 52 weeks, insulin degludec was found to be noninferior to insulin glargine, providing a similar HbA1c-lowering effect (–1.10% vs. –1.18%). However, overall rates of hypoglycemia were significantly lower with insulin degludec (11.09% vs. 13.63%; P = .0359), as were rates of nocturnal hypoglycemia (1.39% vs. 1.84%; P = .0399).

Pharmacology and Pharmacokinetics1,2

Insulin degludec is a modified human insulin in which a single amino acid is deleted and a conjugated hexadecanedioic acid is added via a gamma-L-glutamyl spacer at the amino acid lysine, at position B29 (Figure 1). The hexadecanedioic acid allows the formation of multihexamers in subcutaneous (SC) tissues following administration, creating an SC depot that results in slow insulin release to the systemic circulation. Also, in the circulation, insulin degludec is bound by plasma albumin, further extending its duration. Therefore, insulin degludec has a slow onset of action (30–90 minutes)—similar to that of insulin glargine and detemir—and no peak in activity because of the slow diffusion to the systemic circulation. The duration of action of insulin degludec is reported to be as high as 42 hours, compared with 18 to 26 hours provided by other long-acting insulins (glargine and detemir), making it a once-daily basal insulin. No clinically relevant pharmacokinetic differences were observed in patients with renal or hepatic impairment who received insulin degludec. All insulin products lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins also inhibit lipolysis and proteolysis and enhance protein synthesis.

Figure 1.

Insulin degludec injection

Adverse Reactions and Drug Interactions1,2

The most common adverse reactions associated with insulin degludec in clinical trials were hypoglycemia, allergic reactions, injection-site reactions (including lipodystrophy), itching, rash, edema, and weight gain. Severe, life-threatening, generalized allergy (including anaphylaxis), generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, as may hypokalemia. It may be necessary to adjust insulin degludec doses in patients in whom other drugs that affect glucose metabolism are added. Also, concurrent antiadrenergic drugs may mask the signs and symptoms of hypoglycemia. Insulin degludec should not be used in patients with diabetic ketoacidosis.

Dosage and Administration1,2

Insulin degludec is supplied as an injection for SC administration in FlexTouch pens containing 100 or 200 U/mL of insulin. It should be injected SC once daily, at any time of day, into the thigh, upper arm, or abdomen. To reduce the risk of lipodystrophy, injection sites within the same region should be rotated from one injection to the next. Doses should be individualized based on the patient's metabolic needs, blood glucose–monitoring results, and glycemiccontrol goal. Patients with changes in insulin dosage, coadministration of other glucose-lowering medications, meal patterns, and physical activity, as well as patients with renal or hepatic impairment or hypoglycemia unawareness, should be monitored more closely.