title: Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).
abstract: OBJECTIVE
  Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials.
  
  
  METHODS
  EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA(1c) > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA(1c) < 7% without hypoglycaemia or ≥ 3% increase in body weight.
  
  
  RESULTS
  In this large group of T2DM patients, a second OAD was added at mean HbA(1c) of 8.2 ± 1.3%, with no baseline HbA(1c) difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c) ≥ 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data.
  
  
  CONCLUSIONS
  EDGE demonstrates that in a 'real-life' setting, vildagliptin as second OAD can lower HbA(1c) to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs.
authors: I.G. - Endocrinologie, Campus Gasthuisberg, Leuven, Belgium.
authors: C
authors: C
authors: Mathieu
authors: A H
authors: AH
authors: Barnett
authors: H
authors: H
authors: Brath
authors: I
authors: I
authors: Conget
authors: J J
authors: JJ
authors: de Castro
authors: R
authors: R
authors: Göke
authors: E
authors: E
authors: Márquez Rodriguez
authors: P M
authors: PM
authors: Nilsson
authors: E
authors: E
authors: Pagkalos
authors: A
authors: A
authors: Penfornis
authors: N C
authors: NC
authors: Schaper
authors: S K
authors: SK
authors: Wangnoo
authors: W
authors: W
authors: Kothny
authors: G
authors: G
authors: Bader
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000284:Administration, Oral; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin
references: Diabet Med. 2010 Mar;27(3):318-26
references: 20536495
references: N Engl J Med. 2011 May 5;364(18):1685-7
references: 21542739
references: Diabetes Obes Metab. 2010 Jun;12(6):495-509
references: 20518805
references: Lancet. 1998 Sep 12;352(9131):837-53
references: 9742976
references: Diabetes Obes Metab. 2009 Feb;11(2):157-66
references: 19125777
references: Diabetes Res Clin Pract. 2013 Jun;100(3):e78-81
references: 23538267
references: Diabetes Obes Metab. 2007 Mar;9(2):166-74
references: 17300592
references: Lancet. 1998 Sep 12;352(9131):854-65
references: 9742977
references: Drug Saf. 2006;29(5):385-96
references: 16689555
references: Vasc Health Risk Manag. 2011;7:49-57
references: 21415917
references: Diabetes Care. 2011 Jul;34(7):1481-6
references: 21593294
references: J Am Soc Nephrol. 1993 Nov;4(5):1159-71
references: 8305642
references: Diabetes Care. 2012 Jun;35(6):1364-79
references: 22517736
references: Diabetes Care. 2012 Sep;35(9):e64
references: 22923686
references: Pharmacoepidemiol Drug Saf. 2011 Dec;20(12):1295-302
references: 21793098
references: N Engl J Med. 2008 Oct 9;359(15):1577-89
references: 18784090
references: Diabetologia. 2002 Jul;45(7):S23-8
references: 12136408
references: Diabetes Obes Metab. 2009 Jun;11(6):589-95
references: 19515179
references: Diabetes Obes Metab. 2008 Jan;10(1):82-90
references: 18034842
references: J Clin Epidemiol. 2009 May;62(5):499-505
references: 19348976
references: Trials. 2009 Jun 03;10:37
references: 19493350
references: Diabetes Obes Metab. 2010 Jun;12(6):485-94
references: 20518804