An update on DPP-4 inhibitors in the management of type 2 diabetes

ABSTRACT

Introduction: DPP-4 inhibitors are a class of compounds used for the treatment of type 2 diabetes. The drugs inhibit the degradation of GLP-1, thus amplifying the incretin effect. They have moderate glycemic efficacy, a low propensity of causing hypoglycaemia and are weight neutral. The drugs are often used as second line therapy after metformin.

Areas covered: This review summarizes the available compounds in the market and discusses the novel compounds that are currently under development. Several large cardiovascular outcome trials with some of the compounds have been completed, and their results and implications are considered. Fixed dose combination pills are currently the main focus of research and the contribution of these to the care of patients with diabetes is further discussed.

Expert opinion: The DPP-4 inhibitors have been a successful class in drug development for diabetes. Taken orally and available as fixed dose combinations with metformin or with SGLT-2 inhibitors, they have reached a large market share of over 7 billion dollars. Other than retagliptin, it does not appear that any additional compound will be launched soon. Currently, the main focus is on the development of additional fixed dose combinations with SGLT-2 inhibitors, but the success of these combinations remains to be seen.

KEYWORDS:

• DPP-4 inhibitors
• combination pills
• outcome studies
• sitagliptin
• vildagliptin
• saxagliptin
• alogliptin
• linagliptin
• teneligliptin
• anagliptin
• gemigliptin
• trelagliptin
• omarigliptin
• gosogliptin
• evogliptin
• retagliptin

Declaration of interest

A Cahn reports receipt of consulting fees and payment for lectures from: AstraZeneca, Boehringer Ingelheim, Elli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk and Sanofi. S Cernea received payment for lectures from AstraZeneca, Berlin-Chemie Menarini, Eli Lilly, Novo Nordisk, Sanofi-Aventis, Servier Pharma, for clinical trial Steering Committee meetings as National Lead Investigator for DECLARE-TIMI58 from TIMI Study Group and support for travel to meetings from AstraZeneca, Eli Lilly, Sanofi-Aventis. I Raz is on the advisory boards for AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Limited, Novo Nordisk, Inc., Sanofi, Orgenesis, SmartZyme Innovation Ltd, Labstyle Innovations Ltd, Boehringer Ingelheim; a consultant for: AstraZeneca/Bristol-Meyers Squibb, Insuline Medical, Gili Medical, Kamada Ltd, FuturRx Ltd, Nephrogenex Inc., Diabetes Medical Center (Tel Aviv, Israel); Speaker’s Bureau: AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Johnson & Johnson, Merck Sharp & Dohme Limited, Novartis Pharma AG, Novo Nordisk, Inc., Sanofi, Teva, Boehringer Ingelheim; and a Stock/Shareholder in: Insuline Medical, Labstyle Innovations, Orgenesis, Glucome Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.