In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes

Help your patients navigate
the Road Ahead

TRADJENTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

TRADJENTA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

TRADJENTA has not been studied in patients with a history of pancreatitis, and it is unknown if using TRADJENTA increases
the risk of developing pancreatitis in these patients.

In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes

Efficacy

Monotherapy and Add-On Studies

 
 

As monotherapy and as add-on therapy to metformin, metformin and a sulfonylurea (SU), and basal insulin1-5*

Primary endpoint: Placebo-adjusted mean difference in A1C at 24 weeks

Chart: Placebo-adjusted mean difference in A1C at 24 weeks

TRADJENTA was also studied as an initial combination with pioglitazone. Baseline A1C=8.6%; placebo-adjusted mean difference in A1C at 24 weeks=--0.5% (n=252, CI95%[-0.7,-0.3])1† ††

 

Add-on to Basal Insulin

 
 

As add-on therapy to basal insulin, TRADJENTA provided statistically significant A1C reduction1,2*

With incidence of hypoglycemia similar to placebo


Primary endpoint result: –0.7% placebo-adjusted mean difference in A1C at 24 weeks; TRADJENTA n=618; (FAS [LOCF]; P<0.0001)*

Safety endpoint: Incidence of investigator-reported hypoglycemia1,2†

Chart: Placebo-adjusted mean difference in A1C at 24 weeks
Study Designs
Severe Hypoglycemic Events at 52 Weeks 
TRADJENTA
n(%)
Placebo
n(%)
11 (1.7%)
7 (1.1%)
Mean change from baseline in the daily dose of basal insulin1§‖
  • +0.1 IU for TRADJENTA and +0.4 IU for placebo at 24 weeks
  • +2.5 IU for TRADJENTA and +4.1 IU for placebo at 52 weeks

Study Designs

2-year Noninferiority Study VS. an SU

 
 

In a 2-year noninferiority study, efficacy comparable to glimepiride in patients receiving metformin ≥1500 mg/day
with a lower incidence of hypoglycemia and comparative weight difference1,2*

Primary endpoint result: A1C reduction was demonstrated to be noninferior compared with glimepiride (1-sided noninferiority; P=0.0004). Patients in the FAS (LOCF) population achieved an adjusted mean A1C reduction of 0.2% (n=764) from baseline at 104 weeks vs an adjusted A1C mean reduction of 0.4% with glimepiride (n=755)

A conclusion in favor of the noninferiority of TRADJENTA to glimepiride may be limited to patients with a baseline A1C comparable to those included in the study (66% of patients had baseline A1C <8% and 91% had A1C <9%)

Primary endpoint: Adjusted mean difference in A1C between linagliptin and glimepiride at 104 weeks1*

Chart: Adjusted mean difference in A1C between linagliptin and glimepiride at 104 weeks
Study Designs

Secondary endpoint: Incidence of hypoglycemia1†

Chart: Incidence of hypoglycemia
Study Designs

Secondary endpoint: Adjusted mean body weight (lb) change from baseline over 104 weeks §

Chart: Adjusted mean body weight (lb) change from baseline over 104 weeks
Study Designs
 
  • Patients treated with TRADJENTA were observed to have an adjusted mean decrease in body weight from baseline of 1.4 kg, whereas patients on glimepiride had an adjusted mean increase in body weight of 1.3 kg at 104 weeks, resulting in a comparative weight difference (linagliptin minus glimepiride) of 2.7 kg between the 2 treatment arms.

Data in Adult Patients with Type 2 Diabetes and Severe Renal Impairment

 
 

Statistically significant A1C reductions in adult patients with type 2 diabetes and severe renal impairment1,2*

Placebo-adjusted mean difference in A1C

Chart: Placebo-adjusted mean difference in A1C
Chart: Placebo-adjusted mean difference in A1C
Study Designs  

In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes

Efficacy

 
 

As monotherapy and as add-on therapy to metformin, metformin and a sulfonylurea (SU), and basal insulin1-5*

Primary endpoint: Placebo-adjusted mean difference in A1C at 24 weeks

Chart: Placebo-adjusted mean difference in A1C at 24 weeks

TRADJENTA was also studied as an initial combination with pioglitazone. Baseline A1C=8.6%; placebo-adjusted mean difference in A1C at 24 weeks=--0.5% (n=252, CI95%[-0.7,-0.3])1† ††

 

 
 

As add-on therapy to basal insulin, TRADJENTA provided statistically significant A1C reduction1,2*

With incidence of hypoglycemia similar to placebo


Primary endpoint result: –0.7% placebo-adjusted mean difference in A1C at 24 weeks; TRADJENTA n=618; (FAS [LOCF]; P<0.0001)*

Safety endpoint: Incidence of investigator-reported hypoglycemia1,2†

Chart: Placebo-adjusted mean difference in A1C at 24 weeks
Study Designs
Severe Hypoglycemic Events at 52 Weeks 
TRADJENTA
n(%)
Placebo
n(%)
11 (1.7%)
7 (1.1%)
Mean change from baseline in the daily dose of basal insulin1§‖
  • +0.1 IU for TRADJENTA and +0.4 IU for placebo at 24 weeks
  • +2.5 IU for TRADJENTA and +4.1 IU for placebo at 52 weeks

Study Designs

 
 

In a 2-year noninferiority study, efficacy comparable to glimepiride in patients receiving metformin ≥1500 mg/day
with a lower incidence of hypoglycemia and comparative weight difference1,2*

Primary endpoint result: A1C reduction was demonstrated to be noninferior compared with glimepiride (1-sided noninferiority; P=0.0004). Patients in the FAS (LOCF) population achieved an adjusted mean A1C reduction of 0.2% (n=764) from baseline at 104 weeks vs an adjusted A1C mean reduction of 0.4% with glimepiride (n=755)

A conclusion in favor of the noninferiority of TRADJENTA to glimepiride may be limited to patients with a baseline A1C comparable to those included in the study (66% of patients had baseline A1C <8% and 91% had A1C <9%)

Primary endpoint: Adjusted mean difference in A1C between linagliptin and glimepiride at 104 weeks1*

Chart: Adjusted mean difference in A1C between linagliptin and glimepiride at 104 weeks
Study Designs

Secondary endpoint: Incidence of hypoglycemia1†

Chart: Incidence of hypoglycemia
Study Designs

Secondary endpoint: Adjusted mean body weight (lb) change from baseline over 104 weeks §

Chart: Adjusted mean body weight (lb) change from baseline over 104 weeks
Study Designs
 
  • Patients treated with TRADJENTA were observed to have an adjusted mean decrease in body weight from baseline of 1.4 kg, whereas patients on glimepiride had an adjusted mean increase in body weight of 1.3 kg at 104 weeks, resulting in a comparative weight difference (linagliptin minus glimepiride) of 2.7 kg between the 2 treatment arms.

 
 

Statistically significant A1C reductions in adult patients with type 2 diabetes and severe renal impairment1,2*

Placebo-adjusted mean difference in A1C

Chart: Placebo-adjusted mean difference in A1C
Chart: Placebo-adjusted mean difference in A1C
Study Designs  

In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes

DOSING SIMPLICITY

No dose adjustment required regardless of renal function

Chart: Dosing Simplicity
Chart: Dosing Simplicity
TRADJENTA—A SINGLE-STRENGTH DPP-4i
*Refers to categories of renal impairment.
†One 5-mg tablet, once daily for adult patients with type 2 diabetes.
Primarily nonrenal excretion with 5% eliminated via the kidney and 80% excreted via the bile and gut within 4 days of dosing.
When TRADJENTA is used in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.

In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes

TRADJENTA SAFETY PROFILE

Demonstrated safety profile evaluated in more than 6000 patients

Table: Adverse Reactions
Table: Adverse Reactions
  • Other adverse reactions reported in clinical studies with treatment of TRADJENTA tablets were hypersensitivity (e.g., urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity) and myalgia.
  • In the clinical trial program, pancreatitis was reported in 15.2 cases per 10,000 patient-years of exposure while being treated with TRADJENTA compared with 3.7 cases per 10,000 patient-years of exposure while being treated with comparator (placebo and active comparator, sulfonylurea [SU]). Three additional cases of pancreatitis were reported following the last administered dose of linagliptin.
  • In the placebo-controlled studies, hypoglycemia was reported in 6.6% of patients treated with linagliptin vs 3.6% of patients treated with placebo. When linagliptin was administered in combination with metformin and an SU, 22.9% of patients reported hypoglycemia vs 14.8% of patients administered placebo in combination with metformin and an SU.
  • In the study of patients receiving TRADJENTA as add-on therapy to a stable dose of insulin for up to 52 weeks, no significant difference in the incidence of investigator-reported hypoglycemia was noted compared with placebo (31.4% vs 32.9%, respectively). The incidence of hypoglycemia was also similar in both groups (21.4% TRADJENTA; 22.9% placebo) in the first 24 weeks of the study. At 52 weeks, severe hypoglycemic events were reported in 11 (1.7%) TRADJENTA patients compared with 7 (1.1%) for placebo.
  • In a study of TRADJENTA as add-on to pre-existing antidiabetic therapy in patients with severe renal impairment, the incidence of hypoglycemia was higher in patients treated with linagliptin (63%) vs patients treated with placebo (49%). Severe hypoglycemic events were reported in 4.4% of patients treated with linagliptin vs 4.6% of patients treated with placebo in this trial.

 

In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes

Resources

To help with the road ahead

PC-TJ-0158-PROF-R1
Important Safety Information, Indication and Important Limitations of Use Important Safety Information, Indication
and Important Limitations of Use
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Contraindications

TRADJENTA is contraindicated in patients with a history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity.

WARNINGS AND PRECAUTIONS

Pancreatitis

There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking TRADJENTA. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue TRADJENTA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using TRADJENTA.

Use with Medications Known to Cause Hypoglycemia

Insulin secretagogues and insulin are known to cause hypoglycemia. The use of TRADJENTA in combination with an insulin secretagogue (e.g., sulfonylurea) was associated with a higher rate of hypoglycemia compared with placebo in a clinical trial. The use of TRADJENTA in combination with insulin in subjects with severe renal impairment was associated with a higher rate of hypoglycemia. Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with TRADJENTA.

Hypersensitivity Reactions

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with TRADJENTA. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with TRADJENTA, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue TRADJENTA, assess for other potential causes for the event, and institute alternative treatment for diabetes.

Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema to another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with TRADJENTA.

Severe and Disabling Arthralgia

Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate.

Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRADJENTA or any other antidiabetic drug.

ADVERSE REACTIONS

  • Adverse reactions reported in ≥5% of patients treated with TRADJENTA and more commonly than in patients treated with placebo included nasopharyngitis.
  • Hypoglycemia was more commonly reported in patients treated with the combination of TRADJENTA and sulfonylurea compared with those treated with the combination of placebo and sulfonylurea. When TRADJENTA was administered in combination with metformin and a sulfonylurea, 181 of 792 (22.9%) patients reported hypoglycemia compared with 39 of 263 (14.8%) patients administered placebo in combination with metformin and a sulfonylurea. In patients receiving TRADJENTA as add-on therapy to a stable dose of insulin severe hypoglycemic events were reported in 11 (1.7%) patients compared with 7 (1.1%) for placebo. In a study of TRADJENTA as add-on to pre-existing antidiabetic therapy in patients with severe renal impairment, the incidence of hypoglycemia was higher in patients treated with TRADJENTA (63%) vs placebo (49%).
  • In the clinical trial program, pancreatitis was reported in 15.2 cases per 10,000 patient-years of exposure while being treated with TRADJENTA compared with 3.7 cases per 10,000 patient-years of exposure while being treated with comparator (placebo and active comparator, sulfonylurea). Three additional cases of pancreatitis were reported following the last administered dose of linagliptin.

DRUG INTERACTIONS

The efficacy of TRADJENTA may be reduced when administered in combination with a strong P-glycoprotein or CYP3A4 inducer (e.g., rifampin). Therefore, use of alternative treatments to TRADJENTA is strongly recommended.

USE IN SPECIFIC POPULATIONS

  • There are no adequate and well-controlled studies in pregnant women. Therefore, TRADJENTA should be used during pregnancy only if clearly needed.
  • It is not known whether linagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TRADJENTA is administered to a nursing woman.
  • The safety and effectiveness of TRADJENTA in patients below the age of 18 have not been established.

Indication and Important Limitations of Use

TRADJENTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

TRADJENTA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

TRADJENTA has not been studied in patients with a history of pancreatitis, and it is unknown if using TRADJENTA increases the risk of developing pancreatitis in these patients.

TJ PROF ISI 31AUG2015

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