title: Predictors of response in initial users of metformin and sulphonylurea derivatives: a systematic review.
abstract: OBJECTIVE
  To provide an overview of factors predicting metformin and sulphonylurea treatment response.
  
  
  BACKGROUND
  A large variability between individuals in treatment response to metformin and sulphonylurea derivatives exists. Understanding which factors determine response to these drugs may pave the way for more individualized therapy.
  
  
  METHODS
  We conducted a systematic search in the MEDLINE, Cochrane and EMBASE databases, between 2003 and 2012 for articles assessing demographic and clinical prediction factors of treatment response in initial users of metformin or sulphonylurea. A literature search of articles referenced within the studies identified was also performed. Treatment response was defined as change in HbA1c level, reaching target HbA1c levels or time to treatment change. Studies were assessed on quality, sample size and type of analysis. Results were summarized by tabulating positive, null and negative associations observed for included predictors.
  
  
  RESULTS
  A total of 10 articles (six trial reports and four cohort studies) were obtained, including three of sufficient quality. For metformin, baseline HbA1c , older age, lower BMI and shorter disease duration were found to be predictors of better treatment response in at least three studies of sufficient quality. For sulphonylurea derivatives, baseline HbA1c and shorter duration were identified as predictors of better treatment response in at least two studies of sufficient quality. Race, smoking status, lipid levels, blood pressure, kidney function and comorbidities were not significantly associated with treatment response.
  
  
  CONCLUSIONS
  Several demographic and clinical factors were identified as possible predictors of response to metformin and sulphonylurea, but the number of studies with sufficient quality was small. Generally, early treatment seems important for achieving better glycaemic outcomes.
authors.affiliation: Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.|School of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
authors.forename: D P
authors.initials: DP
authors.lastname: Martono
authors.affiliation: Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Lub
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Hak
authors.affiliation: Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.|Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Wilffert
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Denig
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D016903:Drug Monitoring; D004351:Drug Resistance; D018432:Drug Resistance, Multiple; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D057285:Precision Medicine; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human