Linagliptin

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 also 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 (HbA(1c); 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 antihyperglycaemia agents (metformin and/or a sulfonylurea) or basal insulin (with or without metformin and/or pioglitazone). In terms of lowering HbA(1c), 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.

Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment

“…Linagliptin shows modest oral bioavailability, but is rapidly absorbed [9,10]. The maximum plasma concentration (C max ) at steady state is reached on average 1.5 hours after administration of linagliptin 5 mg, once daily [11].…”

“…Linagliptin half-life (t 1/2 ) is 131 hours [12]. No relevant food effects were observed on the absorption profile of linagliptin [10]. …”

“…More patients receiving linagliptin achieved HbA1c ≤ 7% (30.3%) when compared to voglibose (22.2%) [10]. The percentage of patients achieving a reduction ≥ 0.5% in HbA1c with linagliptin (57.2%) was also greater than those with voglibose (37.7%) (p < 0.0001) [10]. …”

“…In different pharmacokinetic drug-drug interaction studies, linagliptin exhibited low potential for drug interaction [10]. Linagliptin did not change the pharmacokinetic steady state of ethinyl estradiol, levonorgestrel, digoxin, warfarin, glyburide, pioglitazone, simvastatin, and metformin [10].…”

“…Linagliptin did not change the pharmacokinetic steady state of ethinyl estradiol, levonorgestrel, digoxin, warfarin, glyburide, pioglitazone, simvastatin, and metformin [10]. Rifampicin, in turn, can reduce the exposure to linagliptin, suggesting that linagliptin efficacy may be reduced by concomitant use of these two drugs [12].…”