Trajenta Adverse Reactions

Summary of the safety profile: The safety of Trajenta has been evaluated in patients with Type 2 Diabetes Mellitus which in most cases received the target dose of 5 mg.
In the pooled analysis of the placebo-controlled trials, the overall incidence of adverse events in patients treated with placebo was similar to linagliptin 5 mg (63.4% versus 59.1%).
Discontinuation of therapy due to adverse events was higher in patients who received placebo as compared to linagliptin 5 mg (4.3% versus 3.4%).
Pancreatitis was reported more often in patients randomized to linagliptin (7 events in 6,580 patients receiving linagliptin versus 2 events in 4,383 patients receiving placebo).
Due to the impact of the background therapy on adverse events (e.g. on hypoglycaemias), adverse events were analysed based on the respective treatment regimens (monotherapy, add on to metformin, add on to sulphonylurea, and add on to metformin plus sulphonylurea, and add on to insulin, and add on to metformin and SGLT2 inhibitors).
The placebo-controlled studies included studies where linagliptin was given as: monotherapy with short-term duration of up to 4 weeks; monotherapy with ≥ 12 week duration; add on to metformin; add on to sulphonylurea; add on to metformin + sulphonylurea; add on to insulin (with or without metformin); add on to metformin and empagliflozin.
The most frequently reported adverse event was hypoglycaemia observed under the triple combination, linagliptin plus metformin plus sulphonylurea 22.9% vs 14.8% in placebo.
Hypoglycaemias in the placebo-controlled studies (10.9%; N=471) were mild (80%; N=384) or moderate (16.6%; N=78) or severe (1.9%; N=9) in intensity.
Tabulated summary of adverse reactions: Adverse reactions classified by system organ class and MedDRA preferred terms reported in patients who received 5 mg Trajenta in double-blind studies as monotherapy, initial combination therapy or as add-on therapy in clinical trials and adverse reactions identified from post-marketing experience are presented in the table as follows.
The adverse reactions are listed by absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), or very rare (<1/10,000), not known (cannot be estimated from the available data). (See Table 4.)

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Linagliptin cardiovascular and renal safety study (CARMELINA): The CARMELINA study evaluated the cardiovascular and renal safety of linagliptin versus placebo in patients with type 2 diabetes and with increased CV risk evidenced by a history of established macrovascular or renal disease (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). The study included 3494 patients treated with linagliptin (5 mg) and 3485 patients treated with placebo. Both treatments were added to standard of care targeting regional standards for HbA_1c and CV risk factors. At baseline, 57% of patients were treated with insulin, 54% with metformin, and 32% with a sulfonylurea. The overall incidence of adverse events and serious adverse events in patients receiving linagliptin was similar to that in patients receiving placebo. Safety data from this study was in line with previous known safety profile of linagliptin.
In the treated population, severe hypoglycaemic events (requiring assistance) were reported in 3.0% of patients on linagliptin and in 3.1% on placebo. Among patients who were using sulfonylurea at baseline, the incidence of severe hypoglycaemia was 2.0% in linagliptin-treated patients and 1.7% in placebo treated patients. Among patients who were using insulin at baseline, the incidence of severe hypoglycaemia was 4.4% in linagliptin-treated patients and 4.9% in placebo treated patients.
In the overall study observation period adjudicated acute pancreatitis was reported in 0.3% of patients treated with linagliptin and in 0.1% of patients treated with placebo.
In the CARMELINA study, bullous pemphigoid was reported in 0.2% of patients treated with linagliptin and in no patient treated with placebo.