title: Efficacy of vildagliptin versus sulfonylureas as add-on therapy to metformin: comparison of results from randomised controlled and observational studies.
abstract: OBJECTIVE
  Randomised control trials (RCTs) do not always reflect real-life outcomes for glucose-lowering drugs. In this work we compared RCT and real-life data on the efficacy of the dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin or sulfonylureas when added to metformin.
  
  
  METHODS
  Data were pooled from five RCTs examining vildagliptin (n = 2,788) and sulfonylureas (glimepiride [n = 1,259] or gliclazide [n = 433]), added to metformin. For real-life conditions, data were extracted from an observational study examining vildagliptin (n = 7,002) or sulfonylureas (n = 3,702), added to metformin monotherapy. Linear regression analyses were performed between the baseline HbA1c and the change in HbA1c (Δ HbA1c) after 24 weeks.
  
  
  RESULTS
  Baseline HbA1c correlated to Δ HbA1c (r (2) = 0.36, slope = -0.54 [95% CI -0.55, -0.53; p < 0.0001]) for both treatments. With sulfonylureas, the slope of the correlation was steeper in the observational study than in RCTs (interaction coefficient = -0.327, p < 0.001), whereas for vildagliptin, the slope was virtually identical in the observational study and the RCTs (interaction coefficient = 0.024, p = 0.175). For any given baseline HbA1c, Δ HbA1c with sulfonylureas was smaller in real life than in RCTs, whereas Δ HbA1c with vildagliptin was the same.
  
  
  CONCLUSIONS
  When comparing RCT to real-life data, the decrease in HbA1c from baseline with sulfonylurea treatment is smaller in real life than in RCTs, whereas the reduction with vildagliptin is essentially the same, suggesting that the full power of treatment is retained in real life for vildagliptin but not for sulfonylureas, possibly due to fear of hypoglycaemia.
authors.affiliation: Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bader
authors.forename: Anja
authors.initials: A
authors.lastname: Schweizer
authors.forename: James E
authors.initials: JE
authors.lastname: Foley
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D001786:Blood Glucose; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use; D011759:Pyrrolidines / Q000008:administration & dosage / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D000077597:Vildagliptin; D016032:Randomized Controlled Trials as Topic; D064887:Observational Studies as Topic
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D011759:Pyrrolidines; D013453:Sulfonylurea Compounds; D000077597:Vildagliptin