title: Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls.
abstract: OBJECTIVE
  Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all-cause mortality in diabetic patients treated first-line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes.
  
  
  METHODS
  We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first-line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables.
  
  
  RESULTS
  We identified 78,241 subjects treated with metformin, 12,222 treated with sulphonylurea, and 90,463 matched subjects without diabetes. This resulted in a total, censored follow-up period of 503,384 years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person-years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy [survival time ratio (STR) = 1.0], adjusted median survival time was 15% lower (STR = 0.85, 95% CI 0.81-0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58-0.66) in diabetic patients treated with sulphonylurea monotherapy.
  
  
  CONCLUSIONS
  Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first-line therapy and implies that metformin may confer benefit in non-diabetes. Sulphonylurea remains a concern.
authors.affiliation: The Cochrane Institute of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, UK; Cardiff School of Computer Science and Informatics, Cardiff University, Cardiff, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Bannister
authors.forename: S E
authors.initials: SE
authors.lastname: Holden
authors.forename: S
authors.initials: S
authors.lastname: Jenkins-Jones
authors.forename: C Ll
authors.initials: CL
authors.lastname: Morgan
authors.forename: J P
authors.initials: JP
authors.lastname: Halcox
authors.forename: G
authors.initials: G
authors.lastname: Schernthaner
authors.forename: J
authors.initials: J
authors.lastname: Mukherjee
authors.forename: C J
authors.initials: CJ
authors.lastname: Currie
mesh_terms: D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D018579:Patient Selection; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020521:Stroke / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: all-cause mortality; metformin; sulphonylurea; type 2 diabetes