title: Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Clinicians and patients need updated evidence on the comparative effectiveness and safety of diabetes medications to make informed treatment choices.
  
  
  OBJECTIVE
  To evaluate the comparative effectiveness and safety of monotherapy (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT-2] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists) and selected metformin-based combinations in adults with type 2 diabetes.
  
  
  METHODS
  English-language studies from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, indexed from inception through March 2015 (MEDLINE search updated through December 2015).
  
  
  METHODS
  Paired reviewers independently identified 179 trials and 25 observational studies of head-to-head monotherapy or metformin-based combinations.
  
  
  METHODS
  Two reviewers independently assessed study quality and serially extracted data and graded the strength of evidence.
  
  
  RESULTS
  Cardiovascular mortality was lower for metformin versus sulfonylureas; the evidence on all-cause mortality, cardiovascular morbidity, and microvascular complications was insufficient or of low strength. Reductions in hemoglobin A1c values were similar across monotherapies and metformin-based combinations, except that DPP-4 inhibitors had smaller effects. Body weight was reduced or maintained with metformin, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors and increased with sulfonylureas, thiazolidinediones, and insulin (between-group differences up to 5 kg). Hypoglycemia was more frequent with sulfonylureas. Gastrointestinal adverse events were highest with metformin and GLP-1 receptor agonists. Genital mycotic infections were increased with SGLT-2 inhibitors.
  
  
  CONCLUSIONS
  Most studies were short, with limited ability to assess rare safety and long-term clinical outcomes.
  
  
  CONCLUSIONS
  The evidence supports metformin as first-line therapy for type 2 diabetes, given its relative safety and beneficial effects on hemoglobin A1c, weight, and cardiovascular mortality (compared with sulfonylureas). On the basis of less evidence, results for add-on therapies to metformin were similar to those for monotherapies.
  
  
  BACKGROUND
  Agency for Healthcare Research and Quality.
authors.forename: Nisa M
authors.initials: NM
authors.lastname: Maruthur
authors.forename: Eva
authors.initials: E
authors.lastname: Tseng
authors.forename: Susan
authors.initials: S
authors.lastname: Hutfless
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Wilson
authors.forename: Catalina
authors.initials: C
authors.lastname: Suarez-Cuervo
authors.forename: Zackary
authors.initials: Z
authors.lastname: Berger
authors.forename: Yue
authors.initials: Y
authors.lastname: Chu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Iyoha
authors.forename: Jodi B
authors.initials: JB
authors.lastname: Segal
authors.forename: Shari
authors.initials: S
authors.lastname: Bolen
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology; D002423:Cause of Death; D057186:Comparative Effectiveness Research; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin