Efficacy and safety of Jentadueto® (linagliptin plus metformin)

Metformin is the first-choice drug in the management of type 2 diabetes. However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for combined therapy with metformin. Linagliptin shares a similar pharmacodynamic (PD) profile with other gliptins, but has a unique pharmacokinetic (PK) profile characterized by negligible renal excretion.

An extensive literature search was performed to analyze the potential PK/PD interactions between linagliptin and metformin. They are not prone to PK drug-drug interactions. The two compounds may be administered together, either separately or using a fixed-dose combination (FDC) as shown by bioequivalence studies. The addition of linagliptin in patients not well controlled with metformin alone has proven its efficacy in improving glucose levels with a good safety profile. Initial co-administration of linagliptin plus metformin improves glucose control more potently than either compound separately, without hypoglycemia, weight gain or increased metformin-related gastrointestinal side effects.

The linagliptin plus metformin combination may offer some advantages over the classical sulfonylurea-metformin combination. Even if linagliptin is safe in patients with renal impairment, the use of metformin (and thus of the linagliptin plus metformin FDC) is still controversial in this population.