title: Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL-study.
abstract: OBJECTIVE
  To investigate efficacy and safety of vildagliptin compared to other oral antidiabetics in clinical practice in Germany.
  
  
  METHODS
  In this prospective, open, observational study, patients with type 2 diabetes mellitus (T2DM) previously on oral monotherapy were selected by their treating physician to receive either vildagliptin add-on to metformin (cohort 1), vildagliptin + metformin single-pill combination (SPC) (cohort 2) or another dual combination therapy with oral antidiabetic drugs (OADs) (cohort 3). According to routine clinical practice, interim examinations occurred every 3 mo: at baseline, after approximately 3 mo and after approximately 6 mo. Parameters documented in the study included demographic and diagnostic data, history of T2DM, data on diabetes control, vital signs, relevant prior and concomitant medication and disease history. Efficacy was assessed by changes in HbA1c and fasting plasma glucose (FPG) 3 mo and 6 mo after initiation of dual combination therapy. Safety was assessed by adverse event reporting and measurement of specific laboratory values (serum creatinine, total bilirubin, alanine aminotransferase, aspartate aminotransferase, creatine kinase).
  
  
  RESULTS
  Between October 2009 and January 2011, a total of 3881 patients were enrolled in this study. Since 47 patients were withdrawn due to protocol violations, 3834 patients were included in the statistical analysis. There were no relevant differences between the three cohorts concerning age, body weight and body mass index. Average diabetes duration was approximately 6 years and mean HbA1c was between 7.6% and 7.9% at baseline. Antidiabetic treatment was recorded in 3648 patients. Patients were treated with vildagliptin add-on to metformin (n = 603), vildagliptin + metformin (SPC) (n = 2198), and other oral OADs including combinations of metformin with sulfonylurea (n = 370), with glitazones (n = 123), other dipeptidyl peptidase-4 inhibitors (n = 99). After 6 mo of treatment, the absolute decrease in HbA1c (mean ± SE) was significantly more pronounced in patients receiving vildagliptin add-on to metformin (-0.9% ± 0.04%) and vildagliptin + metformin (SPC) (-0.9% ± 0.03%) than in patients receiving other OADs (-0.6% ± 0.04%; P < 0.0001). In addition, significant cohort differences were observed for the improvement in FPG after 6 mo treatment (vildagliptin add-on to metformin: -291 mg/L ± 18.3 mg/L; vildagliptin +metformin (SPC): -305 mg/L ± 9.6 mg/L; other antidiabetic drugs: -209 mg/L ± 14.0 mg/L for (P < 0.0001). Moderate decreases in body weight (absolute difference between last control and baseline: mean ± SE) were observed for patients in all cohorts (vildagliptin add-on to metformin: -1.4 kg ± 0.17 kg; vildagliptin + metformin (SPC): -1.7 kg ± 0.09 kg; other OADs: -0.8 kg ± 0.13 kg). No significant differences in adverse events (AEs) and other safety measures were observed between the cohorts. When performing an additional analysis by age (patients < 65 years vs patients ≥ 65 years), there was no relevant difference in the most common AEs between the two age groups and the AE profile was similar to that of the overall patient population.
  
  
  CONCLUSIONS
  Clinical practice confirms that vildagliptin is an effective and well-tolerated treatment in combination with metformin in T2DM patients.
authors.affiliation: Matthias Blüher, Department of Medicine, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Ira
authors.initials: I
authors.lastname: Kurz
authors.forename: Simone
authors.initials: S
authors.lastname: Dannenmaier
authors.forename: Markus
authors.initials: M
authors.lastname: Dworak
keywords: Combination therapy; Metformin; Observational study; Type 2 diabetes; Vildagliptin