header
For US Healthcare Professionals
Tradjenta Linagliptin Logo

Elderly Man Hero Banner

Safety Data

TRADJENTA has a demonstrated safety profile evaluated in more than 6000 patients.

TRADJENTA Safety Profile

Adverse reactions reported in ≥2% of adult patients treated with TRADJENTA and greater than placebo in placebo-controlled clinical studies of TRADJENTA monotherapy or combination therapy

  TRADJENTA 5 mg n=3625 PLACEBO n=2176
Nasopharyngitis n=254 (7.0%) n=132 (6.1%)
Diarrhea n=119 (3.3%) n=65 (3.0%)
Cough n=76 (2.1%) n=30 (1.4%)
  • Other adverse reactions reported in clinical trials 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.

Incidence of Hypoglycemia

As add-on therapy to basal insulin§ had statistically significant A1C reduction1-5*

With incidence of hypoglycemia similar to placebo.

TRADJENTA provided a placebo-adjusted mean difference in A1C of -0.7% at 24 weeks (primary endpoint, TRADJENTA n=618; FAS [LOCF]; p<0.0001)5*.

Incidence Of Investigator Reported Hypogycemia
Severe Hypoglycemic Events At 52 Weeks
Footnotes
  • * 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.5
  • † 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); +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.
References
  1. Data on file and TRADJENTA Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc.
  2. Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle H-J, 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.
Abbreviations
FAS: full analysis set; FPG: fasting plasma glucose; IU: international units; OAD: oral anti-diabetic; OR: odds ratio; SU: sulfonylurea

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

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

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.