Linagliptin: a Novel Dipeptidyl Peptidase 4 Inhibitor with a Unique Place in Therapy

The dipeptidyl peptidase 4 (DPP-4) inhibitors comprise a promising new class of agent for the management of type 2 diabetes. They possess a range of physiological effects associated with improved glycemic control including stimulation of glucose-dependent insulin secretion and suppression of glucagon secretion, and lower blood glucose levels through different, but potentially complementary, mechanisms to standard oral therapies. Linagliptin is the latest DPP-4 inhibitor to complete pivotal phase 3 trials. The data show that linagliptin provides significant, clinically meaningful and sustained improvements in glycemic control, with an incidence of adverse events similar to placebo and an excellent tolerability profile. In addition, linagliptin has been shown to be weight neutral and, importantly, there was no increased risk of hypoglycemia attributed to linagliptin use in monotherapy or combination therapy with metformin or pioglitazone. A unique characteristic of linagliptin that differentiates it from other members of the class is its primarily nonrenal route of excretion. The linagliptin phase 3 program included several hundred patients with type 2 diabetes and different stages of renal disease and the data suggest that the drug would not need dose adjustment, regardless of the degree of renal impairment. There is a particular need for safe and effective therapeutic agents that can be used when renal function declines. Linagliptin has recently been approved by the US Food and Drug Administration and may find a place in therapy as a treatment option for the significant number of patients in whom metformin and the other DPP-4 inhibitors are either contraindicated or require dose adjustment because of moderate to severe renal impairment.