DPP-IV INHIBITORS


Dipeptidyl peptidase IV (DPP-IV) is an enzyme responsible for the degradation of GLP-1, which is secreted from the intestine in response to food and stimulates insulin secretion in beta-cells. Inhibition of DPP-IV raises GLP-1 and GIP plasma levels leading to enhanced insulin secretion.

Drugs in this class include sitagliptin and vidagliptin.

  • SITAGLIPTIN

    Tradename(s) Januvia™ / Glactiv™ / Xelevia®
    Company(ies) Merck & Co. / Ono Pharmaceuticals
    Available doses 25 mg, 50 mg and 100 mg
    Dose per day once daily
    Side-effects generally well tolerated
    Elimination half-life12.4 hours
    Metabolismprimarly eliminated unchanged
    US patent status expires in 2022
    US FDA status approved October 2006
    EMEA status approved March 2007
    Indication
    Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus (type 2 diabetes). Sitagliptin is indicated for either:
    • Monotherapy
    • Combination therapy with metformin or a peroxisome proliferatoractivated receptor gamma (PPARγ) agonist (e.g., thiazolidinediones) when the single agent does not provide adequate glycemic control.
    Comments
    Merck reported sales of $42M in 2006, $668M in 2007 and $1.4 billion in 2008.

  • VIDAGLIPTIN

    Tradename(s) Galvus®
    Company(ies) Novartis Pharma AG
    Available doses 50 mg
    Dose per day once daily
    Side-effects generally well tolerated
    Elimination half-life 3 hours
    Metabolism hydrolysed in the kidneys to an inactive metabolite
    US patent status to be determined
    US FDA status received "approvable letter" in February 2007
    EMEA status approved September 2007
    Indication

    In Europe, vildagliptin is indicated in the treatment of type 2 diabetes mellitus as dual oral therapy in combination with:
    - metformin, in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin,
    - a sulphonylurea, in patients with insufficient glycaemic control despite maximal tolerated dose of a sulphonylurea and for whom metformin is inappropriate due to contraindications or intolerance,
    - a thiazolidinedione, in patients with insufficient glycaemic control and for whom the use of a thiazolidinedione is appropriate.
    Comments
    Galvus was submitted for US approval in January 2006 as a new therapy to reduce blood sugar levels in patients with type 2 diabetes, both as a monotherapy and in use with other anti-diabetic medicines. In February 2007, the US FDA requested additional data including a clinical study in patients with renal impairment. Novartis is not expected to resubmit data before 2010 .