title: Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis.
abstract: BACKGROUND
  Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea.
  
  
  OBJECTIVE
  To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea.
  
  
  METHODS
  MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases.
  
  
  METHODS
  Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea.
  
  
  METHODS
  Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia.
  
  
  RESULTS
  Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents.
  
  
  CONCLUSIONS
  Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions.
  
  
  CONCLUSIONS
  There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics.
  
  
  BACKGROUND
  Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacăo de Aperfeicoamento de Pessoal de Nível Superior.
authors.affiliation: Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil. jorgeluizgross@gmail.com
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gross
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.forename: Cristiane B
authors.initials: CB
authors.lastname: Leitão
authors.forename: Neil
authors.initials: N
authors.lastname: Hawkins
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Viana
authors.forename: Beatriz D
authors.initials: BD
authors.lastname: Schaan
authors.forename: Lana C
authors.initials: LC
authors.lastname: Pinto
authors.forename: Ticiana C
authors.initials: TC
authors.lastname: Rodrigues
authors.forename: Mirela J
authors.initials: MJ
authors.lastname: Azevedo
mesh_terms: D006801:Humans; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D006442:Glycated Hemoglobin / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds