Trajenta Duo Adverse Reactions

Summary of the safety profile: The safety of linagliptin 2.5 mg twice daily (or its bioequivalent of 5 mg once daily) in combination with metformin has been evaluated in over 6800 patients with type 2 diabetes mellitus (T2DM).
In placebo-controlled studies, more than 1800 patients were treated with the therapeutic dose of either 2.5 mg linagliptin twice daily (or its bioequivalent of 5 mg linagliptin once daily) in combination with metformin for ≥ 12/24 weeks.
In the pooled analysis of the seven placebo-controlled trials, the overall incidence of adverse events (AEs) in patients treated with placebo and metformin was comparable to linagliptin 2.5 mg and metformin (54.3% and 49.0%%). Discontinuation of therapy due to AEs was comparable in patients who received placebo and metformin to patients treated with linagliptin and metformin (3.8% and 2.9%).
Due to the impact of the background therapy on AEs (e,g on hypoglycaemias), adverse events were analysed and displayed based on the respective treatment regimens, add-on to metformin, and add-on to metformin plus sulphonylurea.
The placebo-controlled studies included 7 studies where linagliptin was given as add-on to metformin and 1 study where linagliptin was given as add-on to metformin + sulphonylurea.
Tabulated summary of adverse reactions: The following adverse reactions derived from the use of the linagliptin/metformin combination or the use of the monocomponents (linagliptin or metformin) in clinical trials or from post-marketing experience are shown in the table as follows. Undesirable effects previously reported with one of the individual components may be potential undesirable effects with TRAJENTA DUO even if not observed in clinical trials with this product.
The adverse reactions are listed by system organ class and 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) and not known (cannot be estimated from the available data). (See Table 6.)

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In placebo-controlled studies the most frequently reported adverse reaction for linagliptin plus metformin was diarrhoea (1.6%) with a comparable rate on metformin plus placebo (2.4%).
Adverse reactions reported when linagliptin and metformin were combined with sulphonylurea: When linagliptin and metformin were administered in combination with a sulphonylurea, hypoglycaemia was the most commonly reported adverse reaction (linagliptin plus metformin plus sulphonylurea 23.9% vs 16.0% in the placebo group) and identified as an additional adverse reaction under these conditions. None of the hypoglycaemias episodes were classified as severe (requiring assistance).
Adverse reactions reported when linagliptin and metformin were combined with insulin: When linagliptin and metformin were administrated in combination with insulin, hypoglycaemia was the most frequently reported adverse reactions, but occurred at comparable rate when placebo and metformin were combined with insulin (linagliptin plus metformin plus insulin 29.5% versus 30.9% in the placebo plus metformin plus insulin group) with a low rate of severe (requiring assistance) episodes (1.5% vs 0.9%).
Linagliptin cardiovascular outcome 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; with 54% on metformin. 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.