title: Efficacy of saxagliptin as an add-on to oral monotherapy in the phase 3 clinical development program: predictive factors of the treatment response in type 2 diabetes.
abstract: Saxagliptin, a dipeptidyl peptidase-4 inhibitor, has been the focus of a large clinical development programme, including Phase 3 randomized vs placebo-controlled clinical trials as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control using initial monotherapy (metformin, glibenclamide, thiazolidinedione). This clinical programme has shown saxagliptin to be effective in the control of fasting and postprandial glycemic parameters, in addition to a good overall safety profile. The present paper aims at reviewing the overall short-term and long-term efficacy of saxagliptin in its Phase 3 development program and tries to pinpoint some factors that may be more predictive of treatment response in clinical practice. In individual and pooled analyses of the three pivotal add-on to monotherapy trials, saxagliptin (5mg once daily) led to significant reductions in HbA(1c) from baseline to 24 weeks. Additional analyses showed that reductions in HbA(1c) were maintained in the long-term, notably for 102 weeks, in combination with metformin. Data have also shown that the absolute reduction in HbA(1c) seen with saxagliptine from baseline to Week 24 was numerically greater with an elevated baseline HbA(1c). In these recently published pooled analyses, clinically pertinent reductions in HbA(1c) were also obtained with saxagliptin across a wide range of subgroups of T2D patients when examined either by specific baseline demographic characteristics or by β-cell function indices such as the HOMA-β.
authors.affiliation: Service de diabétologie et d'endocrinologie, université Paris-Diderot Paris-7, hôpital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75475 Paris cedex 10, France; UMR-S Inserm 872 (équipe 8), centre de recherche des Cordeliers, université Pierre-et-Marie-Curie, Paris-6, 15, rue de l'École-de-Médecine, 75006 Paris, France. Electronic address: jean-francois.gautier@sls.aphp.fr.
authors.forename: J-F
authors.initials: JF
authors.lastname: Gautier
authors.affiliation: Polyclinique de médecine interne, hôpital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75475 Paris cedex 10, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Sauvanet
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005215:Fasting; D005502:Food; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C502994:saxagliptin