title: Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone.
abstract: BACKGROUND
  Poor control of type 2 diabetes results in substantial long-term consequences. Studies of new diabetes treatments are rarely designed to assess mortality, complication rates and costs. We sought to estimate the long-term consequences of liraglutide and rosiglitazone both added to glimepiride.
  
  
  METHODS
  To estimate long-term clinical and economic consequences, we used the CORE diabetes model, a validated cohort model that uses epidemiologic data from long-term clinical trials to simulate morbidity, mortality and costs of diabetes. Clinical data were extracted from the LEAD-1 trial evaluating two doses (1.2 mg and 1.8 mg) of a once daily GLP-1 analog liraglutide, or rosiglitazone 4 mg, on a background of glimepiride in type 2 diabetes. CORE was calibrated to the LEAD-1 baseline patient characteristics. Survival, cumulative incidence of cardiovascular, ocular and renal events and healthcare costs were estimated over three periods: 10, 20 and 30 years.
  
  
  RESULTS
  In a hypothetical cohort of 5000 patients per treatment followed for 30 years, liraglutide 1.2 mg and 1.8 mg had higher survival rates compared to the group treated with rosiglitazone (15.0% and 16.0% vs. 12.6% after 30 years), and fewer cardiovascular, renal, and ocular events. Cardiovascular death rates after 30 years were 69.7%, 68.4% and 72.5%, for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively. First and recurrent amputations were lower in the rosiglitazone group, probably due to a 'survival paradox' in the liraglutide arms (number of events: 565, 529, and 507, respectively). Overall cumulative costs per patient, were lower in both liraglutide groups compared to rosiglitazone (US$38,963, $39,239, and $40,401 for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively), mainly driven by the costs of cardiovascular events in all groups.
  
  
  CONCLUSIONS
  Using data from LEAD-1 and epidemiologic evidence from the CORE diabetes model, projected rates of mortality, diabetes complications and healthcare costs over the long term favor liraglutide plus glimepiride over rosiglitazone plus glimepiride.
  
  
  BACKGROUND
  LEAD-1 NCT00318422; LEAD-2 NCT00318461; LEAD-3 NCT 00294723; LEAD-4 NCT00333151; LEAD-5 NCT00331851; LEAD-6 NCT00518882.
authors.affiliation: Pharmaceutical, Outcomes Research and Policy Program, University of Washington, Seattle, USA. sdsull@u.washington.edu
authors.forename: Sean D
authors.initials: SD
authors.lastname: Sullivan
authors.forename: Rafael
authors.initials: R
authors.lastname: Alfonso-Cristancho
authors.forename: Chris
authors.initials: C
authors.lastname: Conner
authors.forename: Mette
authors.initials: M
authors.lastname: Hammer
authors.forename: Lawrence
authors.initials: L
authors.lastname: Blonde
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C057619:glimepiride; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1