This website is intended for US healthcare professionals only.

Please select an option below:

You are now leaving a Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Lilly USA, LLC (Lilly) site. BIPI and Lilly are not responsible for the way information is processed by sites linked to this one. Please review those sites’ privacy policies and terms of use to understand how your information will be processed. Linking to any other site is at your own risk.

Efficacy

In addition to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes. Not for type 1 diabetes or diabetic ketoacidosis.

Thank you for your interest in the efficacy of TRADJENTA. TRADJENTA has been shown to lower A1C in multiple clinical studies that included a variety of adult patients with type 2 diabetes. See details below.

Monotherapy and Add-on Therapy

STATISTICALLY SIGNIFICANT A1C REDUCTIONS AS MONOTHERAPY AND ADD-ON THERAPY

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

A1C Reduction Chart – Monotherapy and Add-on Therapy

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, P<0.0001)1† ††

 

View Study Designs

 

*Prespecified primary analysis of primary endpoint. Full analysis set. (FAS; defined as all randomized patients treated with at least 1 dose of the study drug, with a baseline A1C value, and at least 1 on-treatment A1C value.) The FAS is the basis for the intention-to-treat (ITT) analysis.

†ANCOVA model included treatment and number of prior oral antihyperglycemic drugs (OADs) as class effects, as well as baseline A1C as continuous covariates.

‡0.3% adjusted mean increase from baseline A1C 8.0% with placebo (n=163). 20.9% of patients in the placebo group required use of rescue therapy vs 10.2% of patients in the TRADJENTA group.

§0.15% adjusted mean increase from baseline A1C 8.0% with placebo plus metformin (n=175). 18.9% of patients in the placebo group required use of rescue therapy vs 7.8% of patients in the TRADJENTA group.

||ANCOVA model included treatment as class effect and baseline A1C as continuous covariates.

¶0.1% adjusted mean decrease from baseline A1C 8.1% with placebo plus metformin and an SU (n=262). 13% of patients in the placebo group required the use of rescue therapy vs 5.4% in the TRADJENTA group.

#ANCOVA model included treatment, categorical renal function impairment status, and concomitant OADs as class effects, as well as baseline A1C as continuous covariates.

**0.1% adjusted mean increase from baseline A1C 8.3% with placebo plus basal insulin (n=617). 19.8% of patients in the placebo group required the use of rescue therapy vs 12.6% in the TRADJENTA group at 24 weeks. 50.4% of patients in the placebo group required use of rescue therapy vs 38.2% of patients in the TRADJENTA group at 52 weeks.

††0.6% adjusted mean decrease from baseline A1C 8.6% with placebo plus pioglitazone (n=128). 14.1% of patients treated with placebo plus pioglitazone required rescue therapy vs 7.9% of patients treated with TRADJENTA plus pioglitazone.

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.

Hypoglycemia was more commonly reported in patients treated with the combination of TRADJENTA and an SU compared with those treated with the combination of placebo and an SU. When TRADJENTA was administered in combination with metformin and an SU, 181 of 792 (22.9%) patients reported hypoglycemia compared with 39 of 263 (14.8%) patients administered placebo in combination with metformin and an SU. 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 preexisting antidiabetic therapy in patients with severe renal impairment, the incidence of hypoglycemia was higher in patients treated with TRADJENTA (63%) vs placebo (49%).

References: 1. Data on file and TRADJENTA Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. 2. Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of β‑cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab. 2011;13(3):258‑267. 3. Taskinen MR, Rosenstock J, Tamminen I, et al. Safety and efficacy of linagliptin as add‑on therapy to metformin in patients with type 2 diabetes: a randomized, double‑blind, placebo‑controlled study. Diabetes Obes Metab. 2011;13(1):65‑74. 4. Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24‑week randomized study. Diabet Med. 2011;28(11):1352‑1361. Erratum in: Diabet Med. 2012;29(1):158. 5. Yki‑Järvinen H, Rosenstock J, Durán‑Garcia S, et al. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥52‑week randomized, double‑blind study. Diabetes Care. 2013;36(12):3875‑3881.

Across Various Age Groups Studied

STATISTICALLY SIGNIFICANT A1C REDUCTIONS ACROSS VARIOUS AGE GROUPS STUDIED

Prespecified subgroup analysis: placebo-adjusted mean difference in A1C at week 24 across various age groups studied1*

A1C Reduction Chart – Across Various Age Groups Studied

‡0.02% adjusted mean increase from baseline A1C 8.2% with placebo (n=194).
§0.02% adjusted mean decrease from baseline A1C 8.2% with placebo (n=363).
||0.09% adjusted mean decrease from baseline A1C 8.1% with placebo (n=152).
¶0.03% adjusted mean increase from baseline A1C 8.1% with placebo (n=19).

  • Clinical experience with TRADJENTA has not identified differences in response between the elderly and younger patients; however, greater sensitivity of some older individuals cannot be ruled out.

 
  • Prespecified subgroup analysis on pooled data from the 4 pivotal phase III trails that demonstrated efficacy of Tradjenta® (linagliptin) tablets in adult patients with type 2 diabetes. Since these studies had the same design and duration and comparable eligibility criteria, the data from these studies were pooled to provide supportive evidence of efficacy and to provide the basis for the evaluation of efficacy in subgroups.

  • Adult patients across a broad range of ages achieved statistically significant A1C reductions in 24 weeks.

  • Clinical experience with TRADJENTA has not identified differences in response between the elderly and younger patients; however, greater sensitivity of some older individuals cannot be ruled out.

A1C reductions in patients ≥70 years

PRIMARY ENDPOINT: PLACEBO-ADJUSTED MEAN DIFFERENCE IN A1C AT 24 WEEKS2

A1C Reductions Linagliptin vs. Placebo Graph, Patients 70 Years or Older

Baseline A1C 7.8% for the TRADJENTA-treated group and 7.7% for the placebo group. Full analysis set (FAS), last observation carried forward (LOCF).1

TRADJENTA reduced A1C by 0.6% vs placebo at 24 weeks in patients aged ≥70 years2**††

*Model includes baseline A1C, washout, treatment, study, BMI, subgroup, and treatment-by-subgroup interaction.

†FAS, LOCF.

**P<0.0001.2

††Placebo corrected.2

References: 1. Data on file and TRADJENTA Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. 2. Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9902):1413-1423.

 

Read about dosing for this single-strength
DPP-4i for your adult patients with T2DM

 

Learn more about the safety profile
of TRADJENTA

Adult Patients With Type 2 Diabetes and Severe Renal Impairment

STATISTICALLY SIGNIFICANT A1C REDUCTIONS IN ADULT PATIENTS WITH TYPE 2 DIABETES AND SEVERE RENAL IMPAIRMENT 1,2*

PLACEBO-ADJUSTED MEAN DIFFERENCE IN A1C

A1C Reductions Chart – Placebo-Adjusted Mean Difference in Patients With Type 2 Diabetes and Severe Renal Impairment

View Study Designs

 

*Criteria for renal impairment at screening was eGFR (calculated by MDRD formula): <30 mL/min=severe.

†Model includes treatment, continuous A1C, creatinine clearance at baseline, and background antidiabetic drugs. For the initial 12 weeks of the study, background antidiabetic therapy was kept stable. For the remainder of the study, dose adjustments in antidiabetic background therapy were allowed. Patients with an estimated eGFR of <30 mL/min were eligible to participate in the study.

‡Full analysis set, last observation carried forward.

§0.15% adjusted mean decrease from baseline A1C 8.2% with placebo (n=62).

||0.01% adjusted mean increase from baseline A1C 8.2% with placebo (n=62).

Adverse Events

In general, in the study of adult patients with type 2 diabetes and severe renal impairment, the incidence of adverse events, including severe hypoglycemia, was similar to those reported in other TRADJENTA trials. The observed incidence of hypoglycemia was higher (TRADJENTA, 63%, compared with placebo, 49%) due to an increase in asymptomatic hypoglycemic events, especially during the first 12 weeks when background glycemic therapies were kept stable. Ten TRADJENTA-treated patients (15%) and 11 placebo-treated patients (17%) reported at least 1 episode of confirmed symptomatic hypoglycemia. During the same time period, severe hypoglycemic events were reported in 3 (4.4%) TRADJENTA-treated patients and 3 (4.6%) placebo-treated patients. Events that were considered life-threatening or required hospitalization were reported in 2 (2.9%) patients on TRADJENTA and 1 (1.5%) for placebo.

Renal function, as measured by mean eGFR and creatinine clearance, did not change over 52 weeks' treatment compared to placebo.

References: 1. Data on file and TRADJENTA Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. 2. McGill JB, Sloan L, Newman J, et al. Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind, placebo-controlled study. Diabetes Care. 2013;36(2):237‑244.

Add-On Therapy to Basal Insulin

AS ADD-ON THERAPY TO BASAL INSULIN, TRADJENTA PROVIDED STATISTICALLY SIGNIFICANT A1C REDUCTION 1,2*

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†

Incidence of Hypoglycemia vs Placebo Chart, As Add-On to Basal Insulin

View Study Designs

SEVERE HYPOGLYCEMIC EVENTS AT 52 WEEKS

Tradjenta® vs. Placebo Comparison Chart, Severe Hypoglycemic Events at 52 Weeks

Mean change from baseline in the daily dose of basal insulin1§||

  • +0.6 IU for TRADJENTA and +1.3 IU for placebo at 24 weeks

  • +2.5 IU for TRADJENTA and +4.1 IU for placebo at 52 weeks

 

View Study Designs

 

*ANCOVA model included treatment, categorical renal function impairment status, and concomitant OADs as class effects, as well as baseline A1C as continuous covariates. Mean baseline A1C in the TRADJENTA and placebo groups was 8.3%. There was a 0.1% increase in A1C from baseline with placebo group (n=617) at 24 weeks. 19.8% of patients in the placebo group required the use of rescue therapy vs 12.6% in the TRADJENTA group at 24 weeks. 50.4% of patients in the placebo group required use of rescue therapy vs 38.2% of patients in the TRADJENTA group over at least 52 weeks.

†Investigator-reported hypoglycemia was defined as all symptomatic or asymptomatic episodes with a self-measured blood glucose ≤70 mg/dL.

‡Defined as requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

§Mean total daily insulin dose at baseline: TRADJENTA (42 IU); placebo (40 IU).

||IU=international units.

¶Secondary endpoint. FAS; observed cases including rescue (OR).

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.

References: 1. Data on file and TRADJENTA Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. 2. Yki‑Järvinen H, Rosenstock J, Durán‑Garcia S, et al. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥52‑week randomized, double‑blind study. Diabetes Care. 2013;36(12):3875‑3881.

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: ADJUSTED MEAN DIFFERENCE IN A1C BETWEEN LINAGLIPTIN AND GLIMEPIRIDE AT 104 WEEKS1*

A1C Reduction Linagliptin vs. Glimepiride Graph, As Add-On to Metformin

SU=sulfonylurea

 

View Study Designs

 

Primary endpoint result: A1C reduction was demonstrated to be noninferior with TRADJENTA vs 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 mean A1C reduction of 0.4% with glimepiride (n=755).

A conclusion in favor of the noninferiority of TRADJENTA vs 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%.)

SECONDARY ENDPOINT: INCIDENCE OF HYPOGLYCEMIA1†

Incidence of Hypoglycemia Graph - Tradjenta® vs Glimepiride, As Add-On to Metformin

View Study Designs

SECONDARY ENDPOINT: ADJUSTED MEAN BODY WEIGHT (LB) CHANGE FROM BASELINE OVER 104 WEEKS§

Mean Body Weight Change Graph - Tradjenta® vs Glimepiride, As Add-On to Metformin

 

View 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.

*ANCOVA model included treatment and number of prior OADs as class effects, as well as baseline A1C as continuous covariates. 24.7% of patients in the TRADJENTA group required use of rescue therapy vs 21.5% of patients in the glimepiride group.

†Treated set. Hypoglycemic incidence included both asymptomatic events (not accompanied by typical symptoms of plasma glucose concentration of ≤70 mg/dL) and symptomatic events with typical symptoms of hypoglycemia and plasma glucose concentration of ≤70 mg/dL.

P<0.0001 vs glimepiride.

§Model included continuous baseline A1C, number of prior antidiabetic drugs, baseline body weight, and treatment.

||Actual difference=5.9 lb.

P<0.0001 (difference in the adjusted mean body weight change from baseline at 104 weeks between treatment groups).

References: 1. Data on file and TRADJENTA Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. 2. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380(9840):475-483.

Important Safety Information  

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

Acute pancreatitis, including fatal pancreatitis, has been reported in patients taking TRADJENTA. Take careful notice of potential signs and symptoms of pancreatitis and, if suspected, promptly discontinue 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.

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.

Heart Failure

Heart failure has been observed with two other members of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Consider the risks and benefits of TRADJENTA in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Monitor patients for signs and symptoms. Advise patients of the symptoms of heart failure and to immediately report such symptoms. If heart failure develops consider discontinuation of TRADJENTA.

Use with Medications Known to Cause Hypoglycemia

The use in combination with insulin or insulin secretagogues (e.g., sulfonylurea) increases the risk of hypoglycemia. A lower dose of insulin or insulin secretagogue may be required.

Hypersensitivity Reactions

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

Angioedema has also been reported with other 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 linagliptin as a possible cause for severe joint pain and/or disabling arthralgia and discontinue, if appropriate.

Bullous Pemphigoid

There have been reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue TRADJENTA.

Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRADJENTA.

MOST COMMON ADVERSE REACTIONS (≥5%)

Nasopharyngitis, hypoglycemia (when used in combination with sulfonylurea)

DRUG INTERACTIONS

The efficacy of TRADJENTA may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Alternative treatments should be used.

USE IN SPECIFIC POPULATIONS

Use during pregnancy only if clearly needed. Exercise caution when administering to a nursing woman.

CL-TJ-100001 8.21.17

Please see Prescribing Information and Medication Guide.

Important Safety Information  

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

Acute pancreatitis, including fatal pancreatitis, has been reported in patients taking TRADJENTA. Take careful notice of potential signs and symptoms of pancreatitis and, if suspected, promptly discontinue 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.

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.

Heart Failure

Heart failure has been observed with two other members of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Consider the risks and benefits of TRADJENTA in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Monitor patients for signs and symptoms. Advise patients of the symptoms of heart failure and to immediately report such symptoms. If heart failure develops consider discontinuation of TRADJENTA.

Use with Medications Known to Cause Hypoglycemia

The use in combination with insulin or insulin secretagogues (e.g., sulfonylurea) increases the risk of hypoglycemia. A lower dose of insulin or insulin secretagogue may be required.

Hypersensitivity Reactions

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

Angioedema has also been reported with other 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 linagliptin as a possible cause for severe joint pain and/or disabling arthralgia and discontinue, if appropriate.

Bullous Pemphigoid

There have been reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue TRADJENTA.

Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRADJENTA.

MOST COMMON ADVERSE REACTIONS (≥5%)

Nasopharyngitis, hypoglycemia (when used in combination with sulfonylurea)

DRUG INTERACTIONS

The efficacy of TRADJENTA may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Alternative treatments should be used.

USE IN SPECIFIC POPULATIONS

Use during pregnancy only if clearly needed. Exercise caution when administering to a nursing woman.

CL-TJ-100001 8.21.17

Please see Prescribing Information and Medication Guide.