The Tresiba® molecule is different by design

There are a number of reasons why once-daily Tresiba® may be the right option for your appropriate patients with diabetes starting on or switching to basal insulin, including a slow and steady release and a long duration of action.1-3

Duration of action ▾

Less within-subject variability ▾

Half-life ▾

Duration of action ▾

Less within-subject variability ▾

Half-life ▾

A flat, stable profile

Tresiba® U-100 concentrations remained stable from day to day at steady state1-3


Clinical Dosing Chart

Clinical Dosing Chart

Values are estimated ratios relative to day 10; clinical steady state is defined as >90% of the final plateau level.2

  • The recommended time between dose increases is 3 to 4 days (the same amount of time it takes to reach steady state)1

See study designs below.

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Half life

The Tresiba® half-life is approximately 2X longer than insulin glargine U-1002,4

See how the half-life compares

The basal insulin that gives adult patients the option to change day-to-day dose timing if needed1

Tresiba® U-100 is the only basal insulin proven to last 42 hours—that won’t taper off at the end of the day1,5-8,a

A consistent routine is important, but if life gets in the way of a scheduled dose, Tresiba® provides continued efficacy.1

  • Tresiba® was studied at alternating once-daily dosing intervals of 8 to 40 hours in adult patients1
  • Adult patients who miss a dose of Tresiba® should inject their daily dose during waking hours upon discovering the missed dose, then continue with their regular dosing schedule1
  • Adult patients should wait at least 8 hours between Tresiba® injections1
aAfter the last of 8 once-daily injections (0.4 units/kg).

Less within-subject variability for patients on Tresiba®

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Less within-subject variability for patients on Tresiba®

ONE DOSING INTERVAL

Tresiba® U-100 had 4X less within-subject, day-to-day variability vs insulin glargine U-1003

Calculated using the glucose infusion rate (GIR) profiles of adults with type 1 diabetes (P<0.0001)

One dosing interval (0-24 h) at steady state


Clinical Dosing Chart

Clinical Dosing Chart

The clinical significance of these PK/PD differences has not been established

See study design below.

IN A POST HOC ANALYSIS

Tresiba® U-100 had less within-subject, day-to-day variability when evaluated every 2 hours vs insulin glargine U-1003

Calculated using the glucose infusion rate (GIR) profiles of adults with type 1 diabetes (P<0.0001)

2-hour intervals at steady state over the course of 24 hours


Duration of Action Chart

Duration of Action Chart

The clinical significance of these PK/PD differences has not been established

See study design below.

Tresiba® has the longest half-life of any basal insulin1,7,9,10,b

Tresiba®

Insulin glargine U-100

tertiary_msg

bThe mean half-life of other basal insulins: insulin glargine U-300: 19 hours5; insulin detemir: 5 to 7 hours depending on dose6; NPH: 4.4 hours.10
c13.5-hour half-life for insulin glargine U-100 is based on 0.4 units/kg dose.

Study designs
The Heise, Hermanski, et al Study3

Population: Adults with type 1 diabetes.

Study design: Randomized, double-blind, parallel-group, single-center trial evaluating the within-subject, day-to-day variability and glucose-lowering effect of Tresiba® U-100 (n=27) vs insulin glargine U-100 (n=27) under steady-state conditions. Patients received Tresiba® U-100 or insulin glargine U-100 (0.4 units/kg) once daily for 12 days. The euglycemic clamp was performed on days 6, 9, and 12 of treatment and blood samples were taken throughout each clamp period.

Primary endpoint: To evaluate the within-subject variability of the PD response between Tresiba® U-100 and insulin glargine U-100 based on the area under the glucose infusion rate curve (AUCGIR) during 1 dosing interval (0-24 hours) at steady state. The within-subject, day-to-day PD variability in glucose-lowering effect in the Tresiba® arm was 20% and in the insulin glargine U-100 arm was 82% at steady state.

Secondary PD endpoints: To investigate whether within-subject variability was consistent over 24 hours, the within-subject of AUCGIR in 2-hour intervals (AUCGIR,0-2h,SS' AUCGIR,0-2h,SS' AUCGIR,20-22h,SS' AUCGIR,22-24h,SS) was analyzed in a post-hoc analysis.

The Heise, Korsatko, et al Study2

Population: Adults with type 1 diabetes or type 2 diabetes.

Study design: Post hoc analysis of 5 randomized, double-blind, single-center, phase 1 trials. Patients (n=195) received once-daily doses ranging from 0.4-0.8 U/kg and for 6-12 days, depending on the individual study.

Primary endpoint: Determining the duration and consistency of time to steady state Tresiba® U-100 following once-daily subcutaneous dosing in subjects of varying age and diabetes type.


AUCGIR,0-24h,SS=area under the GIR curve from 0 to 24 hours at steady state; CV=coefficient of variation; PK/PD=pharmacokinetic/pharmacodynamics.

Start your adult patients with diabetes on once-daily Tresiba® today

See dosing

Selected Important Safety Information

Contraindications

  • Tresiba® is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to Tresiba® or one of its excipients

Warnings and Precautions

  • Never Share a Tresiba® FlexTouch® Pen, Needle, or Syringe Between Patients, even if the needle is changed. Patients using Tresiba® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens
  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
  • Hypoglycemia is the most common adverse reaction of insulin, including Tresiba®, and may be life-threatening

Indications and Usage

Tresiba® (insulin degludec injection) is indicated to improve glycemic control in patients 1 year of age and older with diabetes mellitus.

Limitations of Use

Tresiba® is not recommended for treating diabetic ketoacidosis.

Important Safety Information

Contraindications

  • Tresiba® is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to Tresiba® or one of its excipients

Warnings and Precautions

  • Never Share a Tresiba® FlexTouch® Pen, Needle, or Syringe Between Patients, even if the needle is changed. Patients using Tresiba® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens
  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
  • Hypoglycemia is the most common adverse reaction of insulin, including Tresiba®, and may be life-threatening. Increase monitoring with changes to: insulin dose, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with hypoglycemia unawareness or renal or hepatic impairment
  • Accidental mix-ups between basal insulin products and other insulins, particularly rapid-acting insulins, have been reported. To avoid medication errors, always instruct patients to check the insulin label before each injection
  • Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Tresiba®
  • As with all insulins, Tresiba® use can lead to life-threatening hypokalemia, which then may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated
  • Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Tresiba®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered

Adverse Reactions

  • Adverse reactions commonly associated with Tresiba® are hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain

Drug Interactions

  • There are certain drugs that may cause clinically significant drug interactions with Tresiba®.
    • Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
    • Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
    • Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
    • Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine

Please click here for Prescribing Information

 

 

References:

  1. Tresiba [package insert]. Plainsboro, NJ: Novo Nordisk Inc; November 2019.
  2. Heise T, Korsatko S, Nosek L, et al. J Diabetes. 2016;8(1):132-138.
  3. Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Diabetes Obes Metab. 2012;14(9):859-864.
  4. Becker RHA, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. Diabetes Care. 2015;38(4):637-643.
  5. Toujeo [package insert]. Bridgewater, NJ: sanofi-aventis US LLC; March 2019.
  6. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk Inc; March 2020.
  7. Lantus [package insert]. Bridgewater, NJ: sanofi-aventis US LLC; November 2018.
  8. Basaglar [package insert]. Indianapolis, IN: Lilly USA LLC; September 2018.
  9. Heise T, Hövelmann U, Nosek L, et al. Expert Opin Drug Metab Toxicol. 2015;11(8):1193-1201.
  10. Humulin N [package insert]. Indianapolis, IN: Eli Lilly and Company; August 2019.