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Efficacy

TRADJENTA provides statistically significant A1C reduction as monotherapy and add-on therapy.

Placebo Adjusted Mean Difference

Monotherapy and Add-on Therapy

TRADJENTA provides statistically significant A1C reduction as monotherapy and add-on therapy1-6

The efficacy of TRADJENTA has been proven in several clinical trials, as monotherapy2 and as add-on therapy to metformin3, metformin and a sulfonylurea (SU)4, basal insulin5, and pioglitazone6.

Footnotes
  • * 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.
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 M-R, 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 H-J. 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.
  6. Gomis R, Espadero RM, Jones R, Woerle HJ, Dugi KA. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2011;13(7):653-61.

TRADJENTA Monotherapy

A randomized, multicenter, double-blind, placebo-controlled study of treatment-naïve and treatment-experienced adult patients with type 2 diabetes aged 18 to 80 years. Participants were randomized to TRADJENTA 5 mg/day (n=336) or placebo (n=167) for 24 weeks. Primary endpoint was change from baseline A1C at 24 weeks. Secondary endpoints included change in fasting plasma glucose (FPG) and 2-hour postprandial glucose (2hPPG).2

TRADJENTA Add-on to Metformin

(Metformin + TRADJENTA vs Metformin + placebo)

A randomized, double-blind, placebo-controlled, parallel-group study of TRADJENTA in adult patients with type 2 diabetes and insufficient glycemic control despite metformin therapy. Participants were randomized to TRADJENTA 5 mg/day (n=524) or placebo (n=177) in combination with metformin ≥1500 mg/day for 24 weeks. Primary endpoint was change from baseline A1C at 24 weeks. Secondary endpoints included change from baseline in FPG and 2hPPG.3

TRADJENTA Add-on to Metformin + Sulfonylurea (SU)

(Metformin + SU + TRADJENTA vs Metformin + SU + placebo)

A randomized, double-blind, placebo-controlled, parallel-group study of TRADJENTA vs placebo in adult patients with type 2 diabetes and insufficient glycemic control despite treatment with metformin in combination with an SU. Participants were randomized to TRADJENTA 5 mg/day (n=793) or placebo (n=265) as an add-on to existing metformin + SU therapy. Primary endpoint was change from baseline A1C at 24 weeks. Secondary endpoint included the change from baseline in FPG.4

TRADJENTA Add-on to Basal Insulin

(Basal insulin + TRADJENTA vs basal insulin + placebo)

A 52-week, randomized, double-blind, placebo-controlled, parallel-group study of TRADJENTA vs placebo in adult patients with type 2 diabetes and insufficient glycemic control despite treatment with basal insulin therapy. Participants were randomized to TRADJENTA 5 mg/day (n=631) or placebo (n=630) as an add-on to existing basal insulin therapy with or without metformin ± pioglitazone. Primary endpoint was change from baseline A1C at 24 weeks. Secondary endpoints included change from baseline in FPG.5

TRADJENTA Plus Pioglitazone

(Pioglitazone + TRADJENTA vs pioglitizone + placebo)

A randomized, double-blind, placebo-controlled, parallel-group study of TRADJENTA vs placebo in adult patients with type 2 diabetes to assess the efficacy of TRADJENTA in combination with pioglitazone. Patients were randomized to TRADJENTA 5 mg/ day in combination with 30 mg pioglitazone (n=259) or pioglitazone 30 mg plus placebo (n=130) (all administered once daily) for 24 weeks. Primary endpoint was change from baseline A1C at 24 weeks. Secondary endpoints included change from baseline in FPG.6

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.1

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%).1

Elderly Man
Elderly Man With Beard
Elderly Woman

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

TRADJENTA may be considered for A1C reduction in adult patients with T2DM.

Adult Patients With Type 2 Diabetes and Severe Renal Impairment

TRADJENTA provides statistically significant A1C reduction in adult patients with T2D and severe renal impairment1,2*

Placebo Adjusted Mean Difference In A1C
Footnotes
  • * 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.
  • ‡ Full analysis set (FAS), last observation carried forward (LOCF).
  • § 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).

A 52-week, randomized, double-blind, placebo controlled trial in patients with severe renal impairment (eGFR <30 mL/min) of TRADJENTA 5 mg (n=68) compared with placebo (n=65) as add-on to preexisting antidiabetic therapy, including insulin, an SU, glinides, pioglitazone, and α-glucosidase inhibitors.2

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.

Placebo Adjusted Mean Difference In A1C At 24 Weeks

Across Various Age Groups Studied

In a clinical trial, statistically significant A1C reduction, across age groups1

In a prespecified subgroup analysis on pooled data from 4 pivotal phase III trials, adult patients with T2D, across a broad range of ages, achieved statistically significant A1C reduction at 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.

Footnotes
  • * Model includes baseline A1C, washout, treatment, study, BMI, subgroup, and treatment-by-subgroup interaction.1
  • † Full analysis set (ITT), last observation carried forward.1
  • ‡ 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).

24-week, placebo-controlled, double-blind pivotal trials for TRADJENTA included TRADJENTA as monotherapy (n=333), TRADJENTA as add-on to metformin (n=513), TRADJENTA as add-on to metformin + sulfonylurea (n=778), and TRADJENTA in initial combination with pioglitazone (n=252). Data pooled from these four pivotal phase III trials underwent prespecified subgroup analysis (N=1876).

• Pre-specified subgroup analysis on pooled data from the 4 pivotal phase III trials that demonstrated efficacy of TRADJENTA tablets in adult patients with type 2 diabetes. As these studies had the same design and duration and comparable eligibility criteria, the data from the studies were pooled to provide supportive evidence of efficacy and to provide the basis for the evaluation of efficacy in subgroups1

• Adult patients across a broad range of age groups achieved statistically significant A1C reductions at 24 weeks1

• 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 out1

A Non-Inferiority Study vs a Sulfonylurea

In a clinical trial, A1C reduction comparable to glimepiride, in patients receiving metformin ≥ 1500 mg/day1,2*

In a 2-year non-inferiority study, A1C reduction was demonstrated to be non-inferior with TRADJENTA vs glimepiride (1-sided non-inferiority; P=0.0004) with a lower incidence of hypoglycemia and comparative weight difference1,2*

Adjusted Mean Difference In A1C At 104 Weeks
Footnotes

  • *

    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. 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 non-inferiority 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%).1,2

Incidence Of Hypoglycemia
Adjusted Mean Body Weight Change At 104 Weeks
  • † 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.1,2
  • ‡ P<0.0001 vs glimepiride.1,2
  • § Model included continuous baseline A1C, number of prior antidiabetic drugs, baseline body weight, and treatment.1,2
  • || Actual difference=5.9 lb.
  • P<0.0001 (difference in the adjusted mean body weight change from baseline at 104 weeks between treatment groups).1

Secondary Endpoint: A Non-Inferiority Study vs a Sulfonylurea

Patients treated with TRADJENTA had an adjusted mean decrease in body weight from baseline (1.4 kg), whereas patients on glimepiride had an adjusted mean increase in body weight (1.3 kg) at 104 weeks, resulting in a comparative weight difference of 2.7 kg between the two treatment arms.1,2

Active-controlled Study of TRADJENTA vs Glimepiride in Combination With Metformin

A 104-week, double-blind, glimepiride-controlled, non-inferiority study in which adult patients with type 2 diabetes with insufficient glycemic control on metformin therapy were randomized to receive the addition of TRADJENTA 5 mg/day (n=777) or glimepiride, titrated as needed (n=775). Average dose of glimepiride in trial was 3 mg/day (initial dose 1 mg/day; maximum dose 4 mg/day). Primary endpoint in this analysis was the change from baseline in A1C after 104 weeks of treatment.2

Note: Eligible study participants were receiving metformin at a stable dose of 1500 mg/day or more (or a maximum tolerated dose less than 1500 mg/day); dose was unchanged throughout the study.

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.
INDICATION AND 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 is not recommended in patients with type 1 diabetes mellitus.

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.

 

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: Hypersensitivity to linagliptin or any of the excipients in TRADJENTA, reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred.

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.

Hypoglycemia: The use in combination with insulin or insulin secretagogues increases the risk of hypoglycemia. A lower dosage of insulin or insulin secretagogue may be required.

Hypersensitivity Reactions: Discontinue TRADJENTA, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes mellitus. 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 TRADJENTA. Consider TRADJENTA 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. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue TRADJENTA.

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.

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-100060 06.16.2023

Please see Prescribing Information, including Medication Guide.