INTENSIFY WITH XULTOPHY® 100/3.6

DUAL™ VII: Xultophy® 100/3.6 demonstrated a similar A1C reduction vs basal-bolus therapy1

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=252) with basal-bolus therapy (insulin glargine U-100 + insulin aspart [n=254]), both + metformin. The primary endpoint was change in A1C after 26 weeks of treatment. Secondary endpoints included change in laboratory-measured FPG, dose, change in body weight, percent of patients achieving A1C <7%, and episodes of hypoglycemia.1


PRIMARY ENDPOINT


A1C REDUCTION

Xultophy® 100/3.6 demonstrated a similar A1C reduction vs basal-bolus therapy1

The difference in A1C effect observed in the trial may not necessarily reflect the effect that is observed in the care setting where alternative insulin glargine U-100 dosage can be used.

aEstimated treatment difference (ETD) (95% CI): –0.02 (–0.16; 0.12). P<0.0001 confirmed non-inferiority.


SECONDARY ENDPOINTS



INSULIN DOSE

Xultophy® 100/3.6 demonstrated a similar A1C reduction with less insulin vs basal-bolus therapy1

  • The average pretrial insulin glargine U-100 dose was 34 units in the Xultophy® 100/3.6 arm and 33 units in the basal-bolus arm
  • Average end of trial dose was 40 units of Xultophy® 100/3.6 vs 52 units basal + 32 units bolus in the basal-bolus arm
  • Patients could not increase their basal insulin or Xultophy® 100/3.6 dose by more than 4 units per week2


EPISODES OF HYPOGLYCEMIA

Xultophy® 100/3.6 resulted in less episodes of hypoglycemiab vs basal-bolus therapy1

ERR (95% CI): 0.11 (0.08; 0.17). P<0.0001.

  • 89% lower rate with Xultophy® 100/3.6
  • The clinical relevance of the difference in rates of severe hypoglycemia has not been established

bSevere or blood glucose (BG)-confirmed symptomatic hypoglycemia: an event requiring assistance from another person to actively administer carbohydrate, glucagon, or other resuscitative actions or BG-confirmed by a plasma glucose value (<56 mg/dL) with symptoms consistent with hypoglycemia.
PYE=patient-year of exposure.
ERR=estimated rate ratio.

Other adverse reactions reported in ≥5% of patients on Xultophy® 100/3.6 in DUAL™ VII3

Adverse reactions

Xultophy® 100/3.6

Infections and infestations

Upper respiratory tract infection

6.0%

Influenza

7.1%

Gastrointestinal disorders

Nauseac

11.1%

Diarrheac

6.3%

Nervous system disorders

Headache

5.6%

cGastrointestinal adverse events tended to diminish within a few days or weeks on continued treatment.

Adverse reactions

Xultophy® 100/3.6

Infections and infestations

Upper respiratory tract infection

6.0%


Influenza

7.1%


Gastrointestinal disorders

Nausea

11.1%


Diarrhea

6.3%


Nervous system disorders

Headache

5.6%

CHANGE IN BODY WEIGHT

Xultophy® 100/3.6 demonstrated weight reduction vs basal-bolus therapy1

ETD (95% Cl): –7.93 (–9.26; –6.39) P<0.0001.

Weight gain can occur with insulin-containing products, including Xultophy® 100/3.6, and has been attributed to the anabolic effects of insulin.2


SUMMARY


DUAL™ VII RESULTS

Once-daily Xultophy® 100/3.6 vs basal-bolus therapy

insulin glargine U-100 + insulin aspart

insulin glargine U-100 + insulin aspart

Mean A1C reduction1

-1.5%

-1.5%

Number of injections1

1 injection

up to 5 injections

Average insulin dose1

40 units

84 units

Severe or BG-confirmed symptomatic hypoglycemiab reported1

1.1 events/PYE

8.2 events/PYE

Weight change1

-2.0 lb

+5.7 lb



Review the abstract of the DUAL™ VII clinical study

“DUAL™ VII demonstrated that patients on Xultophy® 100/3.6 can achieve similar A1C reductions to those on basal-bolus, and can do so with 1 injection each day versus 4 or 5 injections. This is a huge point of interest to my patients who need to intensify.”

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

“DUAL™ VII demonstrated that patients on Xultophy® 100/3.6 can achieve similar A1C reductions to those on basal-bolus, and can do so with 1 injection each day versus 4 or 5 injections. This is a huge point of interest to my patients who need to intensify.”

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

Dosing and titration

Start your adult patients with type 2 diabetes on once-daily Xultophy® 100/3.6 and show them how to titrate their dose.

Mechanism of Action (MOA)

Find out how insulin degludec and liraglutide work together at the molecular level to control blood glucose levels.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 inadequately controlled on basal insulin (less than 50 units daily) or liraglutide (less than or equal to 1.8 mg daily).

  • 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 has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • Xultophy® 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist.
  • 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.

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. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • 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 receptor agonists.
  • 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.
  • 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), which are PPAR-gamma agonists, should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered.
  • Macrovascular Outcomes: There have been no studies establishing conclusive evidence of macrovascular risk reduction with Xultophy® 100/3.6.

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. Billings LK, Doshi A, Gouet D, et al. Efficacy and safety of IDegLira versus basal-bolus insulin therapy in patients with type 2 diabetes uncontrolled on metformin and basal insulin: the DUAL VII randomized clinical trial. Diabetes Care. 2018;41(5):1009-1016.
  2. Xultophy 100/3.6 [package insert]. Plainsboro, NJ: Novo Nordisk Inc; November 2016.
  3. Billings LK, Doshi A, Gouet D, et al. Efficacy and safety of insulin degludec/liraglutide (IDegLira) versus basal-bolus (BB) therapy in patients with type 2 diabetes (T2D): DUAL VII trial (NCT02420262). Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego, CA.