Saxagliptin for the treatment of type 2 diabetes mellitus: Focus on recent studies

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycemic control without causing weight gain or increasing hypoglycemic risk in patients with type 2 diabetes (T2DM). The efficacy and tolerability of saxagliptin, a once-daily DPP-4 inhibitor, administered as monotherapy, as add-on therapy to metformin, a sulfonylurea, or a thiazolidinedione, and as initial combination therapy with metformin, was demonstrated in pivotal 24-week clinical trials. Additional information about the clinical profile of saxagliptin was recently obtained from extension studies, head-to-head clinical trials, and post-hoc analyses. In extension studies, the efficacy and tolerability of add-on saxagliptin and initial saxagliptin-plus-metformin therapy were maintained for up to 102 weeks. Saxagliptin plus metformin was shown to be non-inferior to glipizide plus metformin in lowering glycated hemoglobin from base-line, with reduced body-weight and lower hypoglycemic risk. Post-hoc analyses indicate that the clinical benefits of saxagliptin extend across demographic subgroups and special populations. A meta-analysis found no evidence for increased cardiovascular risk in T2DM patients exposed to saxagliptin for > 1 year. On the basis of this clinical profile, saxagliptin is an attractive option for initial and add-on therapy for T2DM patients with inadequate glycemic control.

Key words::

• Dipeptidyl peptidase-4 inhibitor
• glycemia
• incretin
• oral antidiabetic drugs
• saxagliptin
• type 2 diabetes mellitus

Declaration of interest: Dr Schwartz has received funds from the following pharmaceutical companies that are involved in the diabetes therapeutic area: Abbott Laboratories; Alteon, Inc.; Amgen, Inc.; Amylin Pharmaceuticals, Inc.; Arena Pharmaceuticals; AstraZeneca (Omnicare); Avanir Pharmaceuticals; Becton, Dickinson and Company; Bertek Pharmaceuticals, Inc. (Covalent); BioRexis Pharmaceutical Corporation; BioStratum, Inc. (PPD); Bristol-Myers Squibb; Covalent Group, Inc.; DexCom, Inc.; E.R. Squibb & Sons, LLC; Eli Lilly and Company; Equidyne Systems, Inc. (JB & Associates); Esperion Therapeutics, Inc.; Exocell, Inc.; Galileo Health Partners; Generex Pharmaceuticals, Inc.; Glaxo; GlaxoSmithKline PLC; Innovex Biosciences; Institute for Diabetes Discovery (Covance); Johnson & Johnson; LifeScan, Inc.; LXN Corporation; Mayo Clinic; MediSense, Inc.; Medtronic MiniMed, Inc.; Merck & Co., Inc.; Metabolex, Inc.; Mitsubishi Pharma Corporation; Nastech Pharmaceutical; Neurobiological Technologies, Inc.; Novartis Pharmaceuticals Corporation; Novo Nordisk; Palatin Technologies, Inc. (Protocare); Pfizer Inc.; Quigley Pharma, Inc.; R.W. Johnson Pharmaceutical Research Institute; Regeneron Pharmaceuticals, Inc.; sanofi-aventis; SmithKline Beecham; Solvay Pharmaceuticals; Squibb-Novo; Takeda Pharmaceutical Company, Ltd.; TheraSense, Inc.; Vivus, Inc.; and Xoma Corporation.

Funding for this review was provided by Bristol-Myers Squibb and AstraZeneca. Technical and editorial support for this manuscript was provided by Diane Kwiatkowski, PhD, Paul Ruest, PhD, and Jennifer Ciafullo, MPH, Quintiles Medical Communications, Parsippany, NJ; and Steven Tiger, PA, and Erica Wehner, RPh, Complete Healthcare Communications, Chadds Ford, PA. Dr Schwartz independently drafted, critically revised and approved the final manuscript.