ADA/EASD Antihyperglycemic Therapy - General Recommendations1

Potential combinations of antihyperglycemic therapy

ADA/EASD Antihyperglycemic Therapy Combinations Chart
The order in the chart is not meant to denote any specific preference.
  • Consider initial therapy at this stage when HbA1c is ≥9% (≥75 mmol/mol).
  • Consider initial therapy at this stage when blood glucose is ≥300–350 mg/dL (≥16.7–19.4 mmol/L) and/or HbA1c ≥10–12% (≥86–108 mmol/mol), especially if patient is symptomatic or if catabolic features (weight loss, ketosis) are present, in which case basal insulin + mealtime insulin is the preferred initial regimen.
  • § Usually a basal insulin (e.g., NPH, glargine, detemir, degludec).

1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140‑149.

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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.



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



There have been 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 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.

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 tablets.


  • 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.


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.


  • There are no adequate and well-controlled studies in pregnant women. 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.


Please see Prescribing Information and Medication Guide.