Last reviewed 2026-04-20 · How we verify

Tradjenta (LINAGLIPTIN)

Tradjenta works by blocking an enzyme that breaks down hormones that help the body release insulin.

Tradjenta (Linagliptin) is a small molecule dipeptidyl peptidase 4 (DPP-4) inhibitor developed by Boehringer Ingelheim. It works by blocking the action of DPP-4, an enzyme that breaks down incretin hormones, thereby increasing insulin release and decreasing glucagon levels. Tradjenta is used to treat type 2 diabetes mellitus and has been FDA-approved since 2011. The commercial status of Tradjenta is complex, with multiple generic manufacturers available, but its original patent remains with Boehringer Ingelheim. Key safety considerations include its long half-life of 129 hours.

At a glance

Mechanism of action

Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha-cells, resulting in reduction in hepatic glucose output.

Approved indications

• Diabetes mellitus type 2

Boxed warnings

• WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1) ]. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see Dosage and Administration (2.2) , Contraindications (4) , Warnings and Precautions (5.1) , Drug Interactions (7) , and Use in Specific Populations (8.6 , 8.7) ]. If metformin-associated lactic acidosis is suspected, immediately discontinue JENTADUETO XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1) ]. WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. ( 5.1 ) Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information. ( 5.1 ) If lactic acidosis is suspected, discontinue JENTADUETO XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. ( 5.1 )

Common side effects

• Hypoglycemia with plasma glucose <54 mg/dL
• Severe hypoglycemia
• Back pain
• Arthralgia
• Upper respiratory tract infection
• Headache
• Cough
• Pain in extremity
• Hypertriglyceridemia
• Hyperlipidemia
• Weight increased
• Constipation

Drug interactions

• carbamazepine
• fosphenytoin
• phenytoin
• rifampicin
• tipranavir

Key clinical trials

• Metformin, Empagliflozin With Sitagliptin vs Linagliptin in Type 2 Diabetes (PHASE4)
• Glycemic Variability of Combination Therapies in T2DM (PHASE4)
• Impact of Pharmacogenetic-Guided Treatment on Type 2 Diabetes. (PHASE4)
• LIGHT-MCI Trial: GLP-1 Agonist, SGLT2 Inhibitor, and DPP-4 Inhibitor for MCI Remission in Type 2 Diabetes (NA)
• A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (PHASE1,PHASE2)
• A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (PHASE1,PHASE2)
• Efficacy and Safety of Madalena Association in the Treatment of Type II Diabetes Mellitus (PHASE3)
• Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study

Patents

Primary sources

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