Trajenta Adverse Reactions

Summary of the safety profile: The safety of Linagliptin (Trajenta) has been evaluated in patients with T2DM which in most cases received the target dose of 5 mg.
In the pooled analysis of the placebo-controlled trials, the overall incidence of AEs in patients treated with placebo was similar to linagliptin 5 mg (63.4% versus 59.1%).
Discontinuation of therapy due to AEs was higher in patients who received placebo as compared to linagliptin 5 mg (4.3% versus 3.4%).
Due to the impact of the background therapy on adverse events (e.g. on hypoglycaemias), adverse events were analysed and displayed based on the respective treatment regimens (monotherapy, add on to metformin, add on to thiazolidinedione (PPARγ agent)), add on to sulphonylurea, and add on to metformin plus sulphonylurea, add on to insulin, and add on to metformin and SGLT2 inhibitors.
The placebo-controlled studies included 28 studies where linagliptin was given either as: monotherapy with short-term duration of up to 4 weeks; monotherapy with ≥ 12 week duration; add on to metformin; initial combination therapy with pioglitazone; add on to sulphonylurea; add on to metformin + sulphonylurea; add on to insulin (with or without metformin and/or pioglitazone and/or sulphonylurea); add on to metformin and empagliflozin.
Adverse reactions classified by SOC and MedDRA preferred terms reported in patients who received 5 mg Linagliptin (Trajenta) in the double-blind studies as monotherapy, initial combination therapy or as add-on therapy are presented per treatment regimen in the table as follows (see Table 3).

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The safety of the combination of linagliptin+metformin+pioglitazone was evaluated in 183 patients. The safety profile was comparable to the profile defined for linagliptin, linagliptin+metformin and linagliptin+pioglitazone as presented in Table 3.
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.
Adverse reactions identified from post-marketing experience: From post-marketing experience the following adverse reactions have been reported: 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 Trials 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 HbA1c 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.