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Starting treatment and titrating Xultophy® 100/3.6

Writing a prescription for Xultophy® 100/3.6 could be a step toward glycemic control for your adult patients with type 2 diabetes. Before prescribing, know the starting dose and see how to titrate Xultophy® 100/3.6.

 

START

In patients naïve to basal insulin or a GLP-1 RA at

10 UNITS

10 units=10 units of insulin degludec and 0.36 mg liraglutide1

In patients converting from basal insulin or a GLP-1 RA at

16 UNITS

16 units=16 units of insulin degludec and 0.58 mg liraglutide1    


Xultophy® 100/3.6 Pen

  • Therapy with basal insulin and liraglutide should be discontinued prior to initiation of Xultophy® 100/3.61

A basal insulin dose is dialed, GLP-1 RA automatically adjusts

The Xultophy® 100/3.6 Pen delivers a fixed-ratio combination in increments of 1 unit

(1 unit=1 unit of insulin degludec and 0.036 mg liraglutide)1



Dose once daily at the same time each day with or without food1


No waiting to inject when removed from the refrigerator1

primary_msg

Glycemic control when starting Xultophy® 100/3.6

A post-hoc analysis of DUAL™ V revealed that patients did not lose FPG control when converting from insulin glargine U-100 to Xultophy® 100/3.6.1,2 In the trial, patients on 20-50 units of insulin glargine U-100 at baseline were started on 16 units of Xultophy® 100/3.6 per day.2

Exploratory prespecified secondary endpoint in DUAL V, a 26-week open-label trial vs insulin glargine U-100, both plus MET

Change in FPG over time1,2

Weeks 4, 8, and 12 were exploratory prespecified endpoints in the trial.

Change in mean FPG for insulin degludec/liraglutide was –50.9 mg/dL; for insulin glargine U-100, –49.9 mg/dL.
NS=not significant.
ETD=estimated treatment difference.

Weeks 4, 8, and 12 were exploratory prespecified endpoints in the trial.

“I know there are concerns within the medical community about taking somebody from a higher basal insulin dose like 30 or 40 units and starting them on a Xultophy® 100/3.6 dose of 16 units. However, the data has already demonstrated that there is no loss of glucose control in those first several weeks while patients are titrating to their goal.”

Jodi Strong, DNP, FNPBC, APNP, CDE, BCARM

“I know there are concerns within the medical community about taking somebody from a higher basal insulin dose like 30 or 40 units and starting them on a Xultophy® 100/3.6 dose of 16 units. However, the data has already demonstrated that there is no loss of glucose control in those first several weeks while patients are titrating to their goal.”

Jodi Strong, DNP, FNPBC, APNP, CDE, BCARM

secondary_msg

TITRATE

Every 3-4 days based on FPG1


Below FPG target range

-2 units

Within FPG target range

0 units

Above FPG target range

+2 units

  • Maximum dose: 50 units=50 units of insulin degludec and 1.8 mg liraglutide1
  • In clinical trials, patients adjusted their dose on Monday and Thursday of each week2


tertiary_msg

PRESCRIBE

Ready to prescribe Xultophy® 100/3.6?

How to prescribe

Dispense 1 box of 5 pens1

NDC 0169-2911-151

NDC 0169-2911-151

Provide a second prescription for pen needles

Provide titration instructions with FPG target range    

NDC 0169-2911-151

Provide a second prescription for pen needles

Provide titration instructions with FPG target range    

Starting dose of 10 units or 16 units1

Provide a second prescription for NovoFine® Plus 32G pen needles

Provide titration instruction with FPG target range

Add Xultophy® 100/3.6 to your ePrescribing system

NDC: 0169-2911-15

Drug name: Xultophy® 100/3.6

Form / Strength: 100 units insulin degludec and 3.6 mg liraglutide per mL, 3 mL

Quantity: 15 mL (5 x 3 mL); 1500 units total

Dosage Form: Solution

The Xultophy® 100/3.6 Pen delivers doses from 10 to 50 units in a single injection with dose increments of 1 unit (1 unit = 1 unit of insulin degludec and 0.036 mg liraglutide).


EOP_callouts_viewed

Using the Xultophy® 100/3.6 Pen

Delivers a fixed-ration combination in increments of 1 unit with no push-button extension.1


Xultophy® 100/3.6 samples

Get your adult patients started toward glycemic control with complimentary samples of Xultophy® 100/3.6.




Study design

DUAL™ V (Study C): A 26-week, randomized, parallel, open-label, treat-to-target trial in adult patients with type 2 diabetes inadequately controlled (A1C 7%-10%) on insulin glargine U-100 (20-50 units) + metformin, comparing the efficacy and safety of Xultophy® 100/3.6 (n=278) with continued up-titration of insulin glargine U-100 (n=279), both + metformin. The primary endpoint was change in A1C after 26 weeks of treatment. Exploratory prespecified endpoints included insulin dose, change from baseline in fasting plasma glucose (FPG) level, 9-point self-measured blood glucose (SMBG) profile, responders for A1C level (predefined targets of <7.0% and ≤6.5%), and for composite targets based on A1C level without hypoglycemia and/or without weight gain.1,2

Selected Important Safety Information

WARNING: RISK OF THYROID C-CELL TUMORS

  • Liraglutide, one of the components of Xultophy® 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy® 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
  • Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Xultophy® 100/3.6 and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Xultophy® 100/3.6.

Indications and Limitations of Use

Xultophy® 100/3.6 (insulin degludec and liraglutide injection) 100 units/mL and 3.6 mg/mL is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

  • Xultophy® 100/3.6 is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise.
  • Xultophy® 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist (GLP-1 RA).
  • Xultophy® 100/3.6 is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
  • Xultophy® 100/3.6 has not been studied in combination with prandial insulin.

Important Safety Information

WARNING: RISK OF THYROID C-CELL TUMORS

  • Liraglutide, one of the components of Xultophy® 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy® 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
  • Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Xultophy® 100/3.6 and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Xultophy® 100/3.6.

Contraindications

  • Xultophy® 100/3.6 is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to Xultophy® 100/3.6, either of the active substances, or any of its excipients. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide, one of the components of Xultophy® 100/3.6.

Warnings and Precautions

  • Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated.
  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide postmarketing. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Xultophy® 100/3.6 promptly and if pancreatitis is confirmed, do not restart. Liraglutide, one of the components of  Xultophy® 100/3.6, has been studied in a limited number of patients with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at a higher risk for development of pancreatitis on liraglutide.
  • Never Share a Xultophy® 100/3.6 Pen Between Patients,  even if the needle is changed. Sharing of the pen poses a risk for transmission of blood-borne pathogens.
  • Hyper- or Hypoglycemia with Changes in Xultophy® 100/3.6 Regimen: Monitor blood glucose in all patients. Changes in Xultophy® 100/3.6 regimen may affect glycemic control. Changes should be made cautiously and under medical supervision. Adjustments in concomitant oral anti-diabetic treatment may be needed.
  • Overdose Due to Medication Errors: Instruct patients to check the label before each injection since accidental mix-ups with insulin containing products can occur. Do not administer more than 50 units of Xultophy® 100/3.6 daily. Do not exceed the 1.8 mg maximum recommended dose of liraglutide or use with other GLP-1 RAs.
  • Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin-containing products, including Xultophy® 100/3.6, and may be life-threatening. Increase monitoring with changes to: dose, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with hypoglycemia unawareness or renal or hepatic impairment.
  • Acute Kidney Injury: Acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis, have been reported postmarketing for liraglutide, usually in association with nausea, vomiting, diarrhea, or dehydration. Advise patients of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion.
  • Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, angioedema, bronchospasm, hypotension, and shock can occur. If a hypersensitivity reaction occurs, discontinue and treat per standard of care. Anaphylaxis and angioedema have been reported with other GLP-1 RAs. Use caution in a patient with a history of anaphylaxis or angioedema with other GLP-1 RAs because it is unknown whether such patients will be predisposed to these reactions with Xultophy® 100/3.6.
  • Acute Gallbladder Disease: In a cardiovascular outcomes trial (LEADER trial) 3.1% of patients treated with liraglutide, one of the components of Xultophy® 100/3.6, versus 1.9% of placebo treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. The majority of events required hospitalization or cholecystectomy. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
  • Hypokalemia: All insulin containing products, including Xultophy® 100/3.6 can lead to life-threatening hypokalemia, which may then cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
  • Fluid Retention and Congestive Heart Failure: Patients using insulin containing products, including Xultophy® 100/3.6, with thiazolidinediones (TZDs) should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered.

Adverse Reactions

  • The most common adverse reactions, reported in ≥5% of patients treated with Xultophy® 100/3.6 are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection.

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment and close monitoring of blood glucose. The signs and symptoms of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine).
  • Liraglutide-containing products, including Xultophy® 100/3.6, cause a delay of gastric emptying, and thereby have the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with liraglutide-containing products.

Use in Specific Populations

  • Xultophy® 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Please click here for Prescribing Information.

 

References:

  1. Xultophy 100/3.6 [package insert]. Plainsboro, NJ: Novo Nordisk Inc; February 2019.
  2. Lingvay I, Pérez Manghi F, García-Hernández P, et al; DUAL V Investigators. Effect of insulin glargine up-titration vs insulin degludec/liraglutide on glycated hemoglobin levels in patients with uncontrolled type 2 diabetes: the DUAL V randomized clinical trial. JAMA. 2016;315(9):898-907.