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Linagliptin

A Review of its Use in the Management of Type 2 Diabetes Mellitus

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An Erratum to this article was published on 22 January 2013

Abstract

Linagliptin (Trajenta®, Tradjenta™, Trazenta™, Trayenta™) is an oral, highly selective inhibitor of dipeptidyl peptidase-4 and is the first agent of its class to be eliminated predominantly via a nonrenal route. Linagliptin is indicated for once-daily use for the treatment of adults with type 2 diabetes mellitus, and a twice-daily fixed-dose combination of linagliptin/metformin (Jentadueto®) is lso available. In this article, the pharmacological, clinical efficacy and tolerability data relevant to the use of linagliptin in patients with type 2 diabetes are reviewed.

The efficacy of oral linagliptin in the treatment of adults with type 2 diabetes has been investigated in several double-blind, multicentre trials. Following 12–24 weeks of treatment, improvements in glycaemic control parameters, including glycosylated haemoglobin (HbA1c; primary endpoint in all trials), were seen with linagliptin relative to placebo when used as monotherapy, initial combination therapy (with metformin or pioglitazone) or add-on therapy to other oral anti-hyperglycaemia agents (metformin and/or a sulfonylurea) or basal insulin (with or without metformin and/or pioglitazone). In terms of lowering HbA1c, linagliptin was more effective than voglibose in a 26-week monotherapy trial and noninferior to glimepiride when used as add-on therapy to metformin in a 104-week study. Additional trials and subgroup analyses of pooled data suggest that linagliptin improves glycaemic control regardless of factors such as age, duration of type 2 diabetes, ethnicity and renal function, and as linagliptin is eliminated primarily via a nonrenal route, it can be used without dosage adjustment in patients with renal impairment of any degree. Oral linagliptin was generally well tolerated and was associated with a low likelihood of hypoglycaemia (except when used in combination with a sulfonylurea) and had little effect on bodyweight.

Further long-term and comparative efficacy and tolerability data are required to help position linagliptin more definitively with respect to other antihyperglycaemia agents. However, clinical data currently available indicate that linagliptin is an effective and generally well tolerated treatment option for use in patients with type 2 diabetes, including those with renal impairment for whom other antihyperglycaemia agents require dosage adjustment or are not suitable.

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    Emma D. Deeks

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Correspondence to Emma D. Deeks.

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Various sections of the manuscript reviewed by: D.S.H. Bell, Southside Endocrinology, University of Alabama, Birmingham, AL, USA; G. Bertino, Department of Internal Medicine and Systemic Diseases, University of Catania-Italy Policlinic, Catania, Italy; G.T. Chew, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; S. Del Prato, Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy; J. Eriksson, Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland and the Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; J. Freeman, Division of Endocrinology and Metabolism, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘linagliptin’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE and EMBASE search terms were ‘linagliptin’ and (‘non insulin dependent diabetes mellitus’ or ‘type 2 diabetes mellitus’ or ‘diabetes mellitus, type 2’). Searches were last updated 23 July 2012.

Selection: Studies in patients with type 2 diabetes mellitus who received linagliptin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Linagliptin, dipeptidyl peptidase-4 inhibitor, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

An erratum to this article is available at http://dx.doi.org/10.1007/s40265-013-0012-8.

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Deeks, E.D. Linagliptin. Drugs 72, 1793–1824 (2012). https://doi.org/10.2165/11209570-000000000-00000

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