1. Tresiba- insulin degludec
Manufacturer: Novo Nordisk
FDA Approval Date: 9/25/2015

2. Tresiba® - insulin degludec Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Tresiba®- insulin degludec
Effectively educate patients on the purpose, proper use and potential adverse effects of Tresiba®- insulin degludec

3. 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].

4. Tresiba® - insulin degludec Clinical Application
Contraindications:
Hypersensitivity to insulin products
Use in DKA
Use during hypoglycemia
Warnings/precautions:
Hypoglycemia
Hypokalemia
Tresiba® [package insert].

5. Tresiba® - insulin degludec Clinical Application
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].

6. Tresiba® - insulin degludec 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
Tresiba®[package insert].

7. Tresiba® - insulin degludec 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
Tresiba®[package insert].

8. Tresiba® - insulin degludec 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
Tresiba®[package insert].

9. Tresiba® - insulin degludec Adverse Effects
*over 1 year of treatment
Tresiba -
insulin degludec
Lantus-
insulin glargine
Hypoglycemia
81%
82%
Nasopharyngitis
14%
Upper respiratory tract infection
13%
Headache 9% 7%
Arthralgia 4% 8%
Diarrhea 6%
Tresiba®[package insert].

10. Tresiba® - insulin degludec Monitoring Parameters
Efficacy Monitoring:
Blood glucose- daily (fasting, meals)
A1c- every 3 months
Toxicity Monitoring:
Blood glucose
Tresiba®[package insert].

11. Tresiba® - insulin degludec Prescription Information
Dosing:
T1DM: ⅓- ½ daily insulin requirement, given once daily (generally daily requirement is Units/kg in insulin-naïve patients
T2DM: Starting dose ~ 10 units once daily
Cost: pricing not determined, will be available Q as a 3mL Flextouch pen.
Tresiba®[package insert].

12. Tresiba® - insulin degludec 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.

13. Tresiba® - insulin degludec 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
Garber A, et al. Lancet. 2012; 379:1498–507.

14. Tresiba® - insulin degludec Literature Review
Included: Type II diabetics, age >18, diagnosed >6 months, HbA1c 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
Garber A, et al. Lancet. 2012; 379:1498–507.

15. Tresiba® - insulin degludec 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)
Garber A, et al. Lancet. 2012; 379:1498–507.

16. Tresiba® - insulin degludec 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
Garber A, et al. Lancet. 2012; 379:1498–507.

17. Tresiba® - insulin degludec Literature Review
Results:
Tresiba –
insulin degludec
Lantus –
insulin glargine
Mean A1c decrease
1.10%
1.18%
Difference of 0.08 (95%CI to 0.21)
Mean decrease in fasting BG
41.4 mg/dl
36.0 mg/dL
Difference of (95%CI to 0.06)
Patients reaching A1c <7%
368 (49%)
124 (50%)
Garber A, et al. Lancet. 2012; 379:1498–507.

18. Tresiba® - insulin degludec 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%)
Garber A, et al. Lancet. 2012; 379:1498–507.

19. Tresiba® - insulin degludec 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
Overall
7437 (11.09)
3120 (13.63)
0.82 ( )
0.0359
Nocturnal
930 (1.39)
422 (1.84)
0.75 ( )
Garber A, et al. Lancet. 2012; 379:1498–507.

20. Tresiba® - insulin degludec 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
Garber A, et al. Lancet. 2012; 379:1498–507.

21. Tresiba® - insulin degludec 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

22. Tresiba® - insulin degludec References
Tresiba [package insert]. Bagsvaerd, Denmark: Novo Nordisk; 2015.
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.