Saxagliptin for the treatment of diabetes - a focus on safety

ABSTRACT

Introduction: The safety of agents used to treat type 2 diabetes (T2D), a chronic disease requiring life-long intervention, is of particular interest. Saxagliptin is a potent and selective DPP-4 inhibitor that has emerged as a therapeutic option for T2D.

Areas covered: Its safety was assessed in a development program of 20 phase 2/3 randomized clinical trials and in SAVOR-TIMI 53 trial that evaluated the cardiovascular outcomes. In order to capture any further safety signals, mainly in the long-term, a post-marketing safety surveillance is ongoing. This paper discusses the tolerability and safety profile of the agent, including cardiovascular, renal, pancreatic, hepatic and bone adverse events.

Expert opinion: Saxagliptin is a safe therapeutic option for patients with T2D, with low risk of hypoglycemia and good tolerability. It demonstrated cardiovascular safety (including in patients with pre-existing cardiovascular disease and/or HF) and safety with respect to all-cause mortality and adverse events of special interest. In SAVOR-TIMI53, saxagliptin was associated with an unexpected increased risk of HF hospitalization, mainly in the first 12 months; a mechanistic explanation for this has not been found. Further research needs to elucidate the effect of antidiabetic drugs on the heart, by including biomarkers and echocardiographic sub-studies within large outcome trials.

KEYWORDS:

• Saxagliptin
• DPP-4 inhibitors
• safety profile
• cardiovascular outcomes

Declaration of interest

S Cernea reports 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-TIMI 58 from TIMI Study Group and support for travel to meetings from AstraZeneca, Eli Lilly, Sanofi-Aventis. A Cahn reports receipt of consulting fees and payment for lectures from: AstraZeneca, Boehringer Ingelheim, Elli Lilly, MSD, Novartis, Novo Nordisk and Sanofi. I Raz reports advisory Board involvement for AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Medscape LLC, Merck Sharp & Dohme Limited, Novo Nordisk, Inc., Sanofi, Orgenesis, SmartZyme Innovation Ltd and Labstyle Innovations Ltd; He has acted as consultant for AstraZeneca/Bristol-Meyers Squibb, Insuline Medical, Gili Medical, Kamada Ltd, FuturRx Ltd. He received speaker’s bureau for AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Johnson & Johnson, Merck Sharp & Dohme Limited, Novartis Pharma AG, Novo Nordisk, Inc., Sanofi, Teva; He owns stock and is shareholder in Insuline Medical, Labstyle Innovations SmartZyme Innovation Ltd, Orgenesis and 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.