title: Comparison of different drugs as add-on treatments to metformin in type 2 diabetes: a meta-analysis.
abstract: BACKGROUND
  Metformin is recommended as first-line treatment in type 2 diabetic patients. Several agents can be used as add-on treatments in metformin monotherapy failure. Most available clinical trials on the hypoglycemic efficacy of different drugs were performed either in monotherapy or in combination with agents other than metformin. Aim of the present meta-analysis is to collect available information on the efficacy of different hypoglycemic drugs, in combination with metformin, in patients failing to metformin, or to other oral monotherapies.
  
  
  METHODS
  An extensive Medline search, together with manual search of references from retrieved articles, was performed to identify randomized clinical trials comparing the efficacy on HbA1c of different agents, compared with placebo or with other active drugs, in combination with metformin, in patients failing to oral hypoglycemic therapy. HbA1c reduction at 16-36 months was considered for meta-analysis.
  
  
  RESULTS
  A total of 27 clinical trials were retrieved. Combining the results of different placebo-controlled trials, sulphonylureas, alpha-glucosidase inhibitors and thiazolidinediones induced a reduction [95%CI] of HbA1c of 0.85 [0.78; 0.94], 0.61 [0.55; 0.67], 0.42 [0.40; 0.44]%, respectively. In direct comparisons, sulphonylureas induced a greater reduction of HbA1c (of 0.17 [0.16; 0.18]%) than thiazolidinediones, and had a similar effect as insulin.
  
  
  CONCLUSIONS
  When combined with metformin, sulphonylureas and alpha-glucosidase inhibitors show a similar efficacy on HbA1c. The effects of drugs used as add-on to metformin monotherapy could be different from those observed in monotherapy.
authors.affiliation: Department of Critical Care Medicine and Surgery, Unit of Geriatrics, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50134 Florence, Italy. mmonami@libero.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Monami
authors.forename: Caterina
authors.initials: C
authors.lastname: Lamanna
authors.forename: Niccolò
authors.initials: N
authors.lastname: Marchionni
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D018579:Patient Selection; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin