tresiba - insulin degludec manufacturer: novo nordisk fda approval date: 9/25/2015

Tresiba- insulin degludec

Manufacturer: Novo Nordisk

FDA Approval Date: 9/25/2015

Tresiba® - insulin degludec

Objectives

• At the end of this presentation participants will be able to:1. Appropriately recommend Tresiba®-

insulin degludec

2. Effectively educate patients on the purpose, proper use and potential adverse effects of Tresiba®- insulin degludec


Clinical Application

• Indications: • Glycemic control in diabetes

• Types I and II

• Place in therapy:• Similar to that of Lantus or Levemir

• Long-acting basal insulin

Tresiba® [package insert].



• Contraindications:• Hypersensitivity to insulin products

• Use in DKA

• Use during hypoglycemia

• Warnings/precautions:• Hypoglycemia

• Hypokalemia

Tresiba® [package insert].



• Pregnancy:• Category C

• No studies in pregnant women• Weigh risk/benefit of using during pregnancy

• Lactation:• Unknown if excreted in breastmilk

• Endogenous insulin is excreted in breastmilk, so mothers may require adjustments in insulin or meal plan when breastfeeding

Tresiba®[package insert].


Drug Facts

• Pharmacology:• Insulin is an endogenous peptide

hormone

• Stimulates cellular glucose uptake and utilization

• Insulin degludec arranges into hexamers after subcutaneous injection that allow it to form a depot



Drug Facts

• Pharmacokinetics:

A Tmax ~ 9 hours

D Protein binding >99%

M No clinically relevant Hepatic/Renal metabolism, cleared by uptake into cells

E T ½: 25hrs, duration of action: 42hrs



Drug Interactions

• No direct drug-drug interactions

• Consider drugs which may alter blood glucose levels or mask/blunt symptoms of hypoglycemia• Sulfonylureas, SGLT2s

• Corticosteroids, thiazide diuretics

• β-blockers, clonidine



Adverse Effects

*over 1 year of treatmentTresiba -insulin

degludec

Lantus-insulin

glargine

Hypoglycemia 81% 82%

Nasopharyngitis 14% 14%

Upper respiratory tract infection 14% 13%

Headache 9% 7%

Arthralgia 4% 8%

Diarrhea 6% 8%



Monitoring Parameters

• Efficacy Monitoring:• Blood glucose- daily (fasting, meals)

• A1c- every 3 months

• Toxicity Monitoring:• Blood glucose



Prescription Information

• Dosing: • T1DM: ⅓- ½ daily insulin requirement, given

once daily (generally daily requirement is 0.2-0.4 Units/kg in insulin-naïve patients

• T2DM: Starting dose ~ 10 units once daily

• Cost: pricing not determined, will be available Q1 2016 as a 3mL Flextouch pen.



Literature Review

BEGIN Basal-bolus Type II

•Purpose: compare insulin degludec to insulin glargine in efficacy and adverse effect profile

•Design: Phase III, randomized, open-label, treat-to-target trial

Garber A, et al. Lancet. 2012; 379:1498–507.


Literature Review

• Primary endpoint: change from baseline in HbA1c concentration after 52 weeks

• Secondary endpoints: change in fasting plasma glucose from baseline, percentage of patients reaching A1c goal of <7%

• Safety assessment: hypoglycemia



Literature Review

• Included: Type II diabetics, age >18, diagnosed >6 months, HbA1c 7.0-10.0 with current insulin treatment for at least 3 months

• Excluded: Use of GLP-1 or rosiglitazone in last 3 months, CV event within previous 6 months, uncontrolled HTN, pregnancy, impaired renal/hepatic function



Literature Review

• Background:Tresiba –

insulin degludec n=744

Lantus – insulin glargine

n=248

Sex, male 405 (54%) 133 (54%)

Race, white 83% 82%

Age (years) 59.2 (9.1) 58.1 (10.0)

A1c 8.3% (0.8) 8.4% (0.9)

Duration of diabetes 13.6 (7.4) 13.4% (6.9)



Literature Review

• Intervention: randomize patients (N=1006) at a 3:1 ratio of insulin degludec:insulin glargine once daily

• Insulin doses were titrated until patient-reported fasting blood sugars on 3 days previous to appointment averaged 70mg/dL-90mg/dL.

• Patients continued for 52 weeks



Literature Review

• Results:

Tresiba – insulin

degludec

Lantus – insulin

glargine Mean A1c decrease

1.10% 1.18% Difference of 0.08 (95%CI -0.05 to 0.21)

Mean decrease in fasting BG

41.4 mg/dl 36.0 mg/dL Difference of -0.29 (95%CI -0.65 to 0.06)

Patients reaching A1c <7%

368 (49%) 124 (50%)



Literature Review

• Safety Outcome: Hypoglycemia

Tresiba – insulin degludec

Lantus – insulin glargine

Severe 34 (5%) 11 (4%)

Overall 609 (81%) 206 (82%)

Nocturnal 298 (40%) 119 (47%)



Literature Review

Safety outcome: hypoglycemia (individual episodes)

Tresiba – insulin

degludec

Lantus – insulin

glargine

Rate ratio insulin degludec: insulin glargine (95% CI)

P-value

Severe (rate per PYE)

41 (0.06) 12 (0.05) N/A N/A

Overall (rate per PYE)

7437 (11.09) 3120 (13.63) 0.82 (0.69-0.99) 0.0359

Nocturnal (rate per PYE)

930 (1.39) 422 (1.84) 0.75 (0.58-0.99) 0.0359



Literature Review

BEGIN Basal-bolus Type II

•Conclusion: Insulin degludec is non-inferior to insulin glargine in HbA1c lowering

•May have benefit of reduced rates of nocturnal hypoglycemia and hypoglycemia overall



Summary• Tresiba, insulin degludec, is a new long-acting insulin

similar in administration and dosing to Levemir and Lantus. Insulin degludec forms hexamers after injection.

• Suggested monitoring with home glucose and A1c are similar to other diabetes agents

• Hypoglycemia, injection site reactions, and weight gain are similar to other insulins

• Does not have any true drug-drug interactions, caution use with agents which may further lower glucose, offset glucose lowering effect, or mask Sx hypoglycemia

• Isulin degludec will be available in early 2016 in 3mL “Flextouch” pens


References

1. Tresiba [package insert]. Bagsvaerd, Denmark: Novo Nordisk; 2015.

2. Garber A, King A et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes. Lancet. 2012; 379:1498–507.

tresiba - insulin degludec manufacturer: novo nordisk fda approval date: 9/25/2015

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