title: Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study.
abstract: OBJECTIVE
  Individual sulfonylureas (SUs) and metformin have, in some studies, been associated with unequal hypoglycaemic, cardiovascular and mortality risks when used as monotherapy in type 2 diabetes. We investigated the outcomes in patients treated with different combinations of SUs and insulin vs a combination of metformin and insulin in a retrospective nationwide study.
  
  
  METHODS
  All Danish individuals using dual therapy with SU + insulin or metformin + insulin without prior myocardial infarction (MI) or stroke were followed from 1 January 1997 to 31 December 2009 in nationwide registries. Risks of all-cause mortality, cardiovascular death, hypoglycaemia and a composite endpoint of MI, stroke and cardiovascular death were compared. Rate ratios (RR) [95% CIs] were calculated using time-dependent multivariable Poisson regression analysis.
  
  
  RESULTS
  A total of 11,081 patients used SU + insulin and 16,910 used metformin + insulin. Patients receiving metformin + insulin were younger and had less comorbidity and a longer history of glucose-lowering treatment. SU + insulin was associated with higher mortality rates compared with metformin + insulin (76-126 vs 23 per 1,000 person-years). In adjusted analyses, SU + insulin was associated with increased all-cause mortality (RR 1.81 [1.63, 2.01]), cardiovascular death (RR 1.35 [1.14, 1.60]) and the composite endpoint (RR 1.25 [1.09, 1.42]) compared with metformin + insulin. Hypoglycaemia was more frequent with SU + insulin than with metformin + insulin (17-23 vs six events per 1,000 person-years) and was associated with increased mortality (RR 2.13 [1.97, 2.37]). There were no significant differences in risk between individual SUs in combination with insulin.
  
  
  CONCLUSIONS
  In combination with insulin, the use of SUs was associated with increased mortality compared with metformin. There were no significant risk differences between SUs.
authors.affiliation: The Heart Centre, Department of Cardiology, University Hospital Rigshospitalet, 9441, Blegdamsvej 9, 2100, Copenhagen, Denmark, ulrik_mogensen@hotmail.com.
authors.forename: Ulrik M
authors.initials: UM
authors.lastname: Mogensen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersson
authors.forename: Emil L
authors.initials: EL
authors.lastname: Fosbøl
authors.forename: Tina K
authors.initials: TK
authors.lastname: Schramm
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Nikolai M
authors.initials: NM
authors.lastname: Scheller
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Gislason
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
mesh_terms: D000328:Adult; D000368:Aged; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality; D012042:Registries; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin