SWITCH 2: A separate study designed to further evaluate the safety profile of Tresiba® U-100

Hypoglycemia rates of Tresiba® U-100 were compared to insulin glargine U-1001

Primary endpoint: Rate of severe or BG-confirmed symptomatic hypoglycemiaa events in adult patients with type 2 diabetes in the maintenance period

Patient population was considered to be at increased risk for hypoglycemia

Tresiba® SWITCH 2 Trial Primary Endpoint Results

Tresiba® U-100


185.6 events

per 100 patient-years1,b



22.5%

of patients experienced severe or BG-confirmed symptomatic hypoglycemia1,a,c


Insulin glargine U-100

Insulin glargine U-100

265.4 events

per 100 patient-years1,b

31.6%

of patients experienced severe or BG-confirmed symptomatic hypoglycemia1,a,c


Insulin glargine
U-100


Insulin glargine U-100

265.4 events

per 100 patient-years1,b



31.6%

of patients experienced severe or BG-confirmed symptomatic hypoglycemia1,a,c

Achievement icon

Achieved with similar glycemic control: Tresiba® U-100 vs insulin glargine U-100

  • In the separate, type 2 diabetes adult trials within the BEGIN clinical trial program, the percentage of patients experiencing at least 1 episode ranged from 0% to 4.5% for severe hypoglycemia and 28.5% to 80.9% for Novo Nordisk-defined hypoglycemia in trials with Tresiba® U-100 ± OADs or in a basal bolus regimen2,d,e
  • The American Diabetes Association classifies hypoglycemia <54 mg/dL as clinically significant and sufficiently low to indicate serious, clinically important hypoglycemia3

aBG-confirmed symptomatic hypoglycemia was defined as a BG measurement of <56 mg/dL with symptoms; nocturnal hypoglycemia was defined as any episode occurring between 12:01 AM and 5:59 AM, both inclusive; and severe hypoglycemia was defined per American Diabetes Association 2013 guidelines.

b
Rate difference: –23.66 episodes per 100 patient-years [95% Cl; –33.98 to –13.33].

c
Difference in proportions: –9.1% [95% Cl: –13.1% to –5.0%].

d
Severe hypoglycemia: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.2

e
Novo-Nordisk-defined hypoglycemia: a severe hypoglycemia event or an event where laboratory or self-measured glucose calibrated to plasma was <56 mg/dL or where whole blood glucose was <50 mg/dL (ie, with or without the presence of hypoglycemic symptoms).2

SWITCH 2 study design1

Hypoglycemia rates of Tresiba® U-100 and insulin glargine U-100 were compared in a randomized, double-blind, crossover study1

20% dose reduction

from twice-daily dosing. If switching from once-daily dosing, the starting dose was the pretrial dose.f

721 adult patients

with type 2 diabetes taking basal insulin ± OADs.

  • Patient population was considered to be at increased risk for hypoglycemia.

Hypoglycemia may be happening more often than you think

Treatment arm 1

Tresiba® SWITCH 2 study design

Treatment arm 2

Tresiba® SWITCH 2 study design
Tresiba®: A1C reduction chart in Type 2 Diabetes patients
Tresiba® SWITCH 2 study design

A1C noninferiority in both treatment periods was a prerequisite1

  • Primary endpoint achieved: Tresiba® U-100 demonstrated superiority vs insulin glargine U-100 in terms of rates of severe or BG-confirmed symptomatic hypoglycemica episodes during the maintenance period of each treatment period
  • This study design ensured that all patients were exposed to each trial medication for the same amount of time
  • Mean A1C at the end of treatment period 1: Tresiba®  U-100, 7.06%; insulin glargine U-100, 6.98%1
  • Mean A1C at the end of treatment period 2: Tresiba® U-100, 7.08%; insulin glargine U-100, 7.11%1

All patients required to meet ≥1 of these criteria for developing hypoglycemia:

  • ≥1 episode of severe hypoglycemiag in previous year
  • Moderate chronic renal failure (eGFR: 30 to 59 mL/min/1.73 m2)
  • Hypoglycemic symptom unawareness
  • Insulin exposure >5 years
  • Episode of hypoglycemiah within previous 12 weeks

fThe starting dose for treatment period 2 was the dose from the end of treatment period 1.

g
Based on ADA definition.

h
Symptoms and/or BG level ≤70 mg/dL.

Secondary endpoints achieved1

Secondary confirmatory endpoints

  • The rate of nocturnal symptomatic hypoglycemiaduring the maintenance period was 42% lower with Tresiba® U-100 vs insulin glargine U-100 (55.2 vs 93.6 episodes/100 PYE, respectively; ERR=0.58 [95% CI, 0.46 to 0.74]; P<0.001; rate difference, –7.41 episodes/100 PYE [95% CI, –11.98 to –2.85])
  • The rate of severe hypoglycemiaduring the maintenance period was 46% lower with Tresiba® U-100 vs insulin glargine U-100 (5.3 vs 9.1 episodes/100 PYE, respectively; ERR=0.54 [95% CI, 0.21 to 1.42]; P=not significant; rate difference, –1.18 episodes/100 PYE [95% CI, –2.77 to –0.41])
  • The percentage of patients experiencing at least 1 episode of severe hypoglycemia in the maintenance period was: Tresiba® U-100 1.6%; insulin glargine U-100 2.4% (P=not significant)

Achieved with similar glycemic control: Tresiba® U-100 vs insulin glargine U-100

iNocturnal hypoglycemia was defined as any episode occurring between 12:01 AM and 5:59 AM, both inclusive; and severe hypoglycemia was defined per American Diabetes Association 2013 guidelines. 

BG=blood glucose; OADs=oral antidiabetic drugs.

Once-daily Tresiba®: Provide your patients with proven A1C control2

Selected 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 Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens
  • Monitor blood glucose in all patients treated with insulin. Changes in insulin may affect glycemic control. These changes should be made cautiously and under medical supervision. 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

Indications and Usage

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 or for pediatric patients requiring less than 5 units of Tresiba®.

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 Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens
  • Monitor blood glucose in all patients treated with insulin. Changes in insulin may affect glycemic control. These changes should be made cautiously and under medical supervision. 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 Prescribing Information.

 

References:

  1. Wysham C, Bhargava A, Chaykin L, et al. JAMA. 2017;318 (1):45-56.
  2. Tresiba [package insert]. Plainsboro, NJ: Novo Nordisk Inc; August 2018.
  3. Cefalu WT. Diabetes Care. 2018;41(suppl 1):S55-S64. https://doi.org/10.2337/dc18-S006.