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Important Safety Information | Patient Site
Prescribing Information
Tresiba® (insulin degludec injection) 100 U/mL, 200 U/mL logo

Prescribing Information
Important Safety Information | Patient Site

DEVOTE: a landmark safety outcomes trial for Tresiba® U-1001

The landmark DEVOTE study compared Tresiba® U-100 vs insulin glargine U-100 in adults with T2D and ASCVD.1,2 

Results     |     Study design

Results

Study design

In patients with T2D and ASCVD

DEVOTE is the first safety outcomes trial evaluating the noninferiority in risk of major adverse cardiovascular events (MACEa) with Tresiba® U-100 vs insulin glargine U-100.1,2 Tresiba® U-100 achieved the primary composite outcome, demonstrating no increased risk of MACE vs insulin glargine U-100.1 The secondary confirmatory endpoints compared rates and incidence of severeb hypoglycemia between the 2 products.1

Percentage of patients experiencing MACE1,a:

8.5% in the Tresiba® U-100 group

9.3% in the insulin glargine U-100 group

aMACE=cardiovascular death, nonfatal MI, or nonfatal stroke. 
bSevere hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions and during which plasma glucose concentration may not have been available, but where neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration.1

Secondary confirmatory endpoint

In adult patients with type 2 diabetes and ASCVD

Tresiba® U-100 is the only basal insulin that has demonstrated significantly lower rates of severe hypoglycemia vs insulin glargine U-1001,3-6

Rate of severe hypoglycemia events1

Tresiba® U-100

3.70 events

per 100 patient-yearsc

4.9%

of patients experienced ≥1 severe hypoglycemia event(s)d

40% lower rate of hypoglycemia

Insulin glargine U-100

6.25 events

per 100 patient-yearsc

6.6%

of patients experienced ≥1 severe hypoglycemia event(s)d

cEstimated rate ratio: 0.60 (95% CI, 0.48 to 0.76); P<0.001 for superiority.1,2
dAbsolute difference: 1.7%. Estimated odds ratio, 0.73 (95% CI, 0.60 to 0.89); P<0.001 for superiority.1,2

Glycemic control between the 2 groups was similar at baseline and throughout the trial.2

Study design

DEVOTE: a landmark safety outcomes trial for Tresiba® U-100

DEVOTE was a landmark treat-to-target trial of 7637 patients with inadequately controlled type 2 diabetes and ASCVD.1

7637 patients

Inclusion criteria1,2,e:

  • Type 2 diabetes1
  • Current treatment with ≥1 oral or injectable antidiabetic agent2
  • A1C ≥7.0% OR A1C <7.0% and current treatment with ≥20 U/day basal insulin2
  • Age ≥50 years and ≥1 coexisting cardiovascular or renal condition OR age ≥60 years and ≥1 cardiovascular risk factor1,2

Exclusion criteria7,e:

  • Acute coronary or cerebrovascular event in previous 60 days
  • Planned coronary, carotid, or peripheral artery revascularization
  • Chronic heart failure NYHA class IV
  • Current hemodialysis or peritoneal dialysis or eGFR <30 mL/min/1.73 m2 per CKD-EPI
  • End-stage liver disease

eThis is not an exhaustive list of the inclusion and exclusion criteria.

1 to 1 randomized study in DEVOTE

Duration 2.0 years (median)

Primary composite endpoint

Time to first MACE composed of:

Primary composite endpoint

CV death

Primary composite endpoint

Nonfatal MI

Primary composite endpoint

Nonfatal stroke

FPG target was 71 to 90 mg/dL with an alternative target of 90 to 126 mg/dL for vulnerable patients, at investigators’ discretion.2,f

fPatients determined their FPG by performing 3 pre-breakfast SMBG tests on the 2 days before and on the day of dose adjustment each week. The lowest of the 3 pre-breakfast SMBG values was used to adjust their dose of basal insulin each week.

Secondary confirmatory endpoints:
The number and incidence of severe hypoglycemic events1

­Patient characteristics at baseline1,2:

  • Mean age: 65 years1
  • Mean diabetes duration: 16.4 years1
  • Mean A1C: 8.4%1
  • % of patients on insulin therapy: 83.92

Change in A1C level2:
There was no significant difference between treatment groups throughout the trial; at 24 months, A1C was 7.5% in both groups. ETD 0.01% (95% CI, –0.05 to 0.07); P=0.78 in post hoc analysis.

­ASCVD=atherosclerotic cardiovascular disease; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; CV=cardiovascular; eGFR=estimated glomerular filtration rate; MI=myocardial infarction; NYHA=New York Heart Association; T2D=type 2 diabetes.

In a separate study designed to further evaluate the safety profile of Tresiba® U-100

Find out what SWITCH 2 revealed about the efficacy and safety of Tresiba®

Indications and Usage for Tresiba® (insulin degludec injection) 100 U/mL, 200 U/mL

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 Tresiba® Prescribing Information.

References:

  1. Tresiba [package insert]. Plainsboro, NJ: Novo Nordisk Inc; November 2019.
  2. Marso SP, McGuire DK, Zinman B, et al. N Engl J Med. 2017;377(8):723-732.
  3. Levemir [package insert]. Plainsboro, NJ: Novo Nordisk Inc; March 2020.
  4. Lantus [package insert]. Bridgewater, NJ: sanofi-aventis US LLC; November 2019.
  5. Toujeo [package insert]. Bridgewater, NJ: sanofi-aventis US LLC; November 2019.
  6. Basaglar [package insert]. Indianapolis, IN: Lilly USA LLC; November 2019.
  7. Marso SP, McGuire DK, Zinman B, et al. N Engl J Med. 2017;376(suppl):1-70.