title: Early Glycemic Control and Magnitude of HbA1cReduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators.
abstract: We investigated the association of early achieved HbA1clevel and magnitude of HbA1creduction with subsequent risk of cardiovascular events or death in patients with type 2 diabetes who initiate metformin.
  
  
  
  This was a population-based cohort study including all metformin initiators with HbA1ctests in Northern Denmark, 2000-2012. Six months after metformin initiation, we classified patients by HbA1cachieved (<6.5% or higher) and by magnitude of HbA1cchange from the pretreatment baseline. We used Cox regression to examine subsequent rates of acute myocardial infarction, stroke, or death, controlling for baseline HbA1cand other confounding factors.
  
  
  
  We included 24,752 metformin initiators (median age 62.5 years, 55% males) with a median follow-up of 2.6 years. The risk of a combined outcome event gradually increased with rising levels of HbA1cachieved compared with a target HbA1cof <6.5%: adjusted hazard ratio (HR) 1.18 (95% CI 1.07-1.30) for 6.5-6.99%, HR 1.23 (1.09-1.40) for 7.0-7.49%, HR 1.34 (1.14-1.57) for 7.5-7.99%, and HR 1.59 (1.37-1.84) for ≥8%. Results were consistent for individual outcome events and robust by age-group and other patient characteristics. A large absolute HbA1creduction from baseline also predicted outcome: adjusted HR 0.80 (0.65-0.97) for Δ = -4, HR 0.98 (0.80-1.20) for Δ = -3, HR 0.92 (0.78-1.08) for Δ = -2, and HR 0.99 (0.89-1.10) for Δ = -1 compared with no HbA1cchange (Δ = 0).
  
  
  
  A large initial HbA1creduction and achievement of low HbA1clevels within 6 months after metformin initiation are associated with a lower risk of cardiovascular events and death in patients with type 2 diabetes.
authors.affiliation: Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Svensson
authors.affiliation: Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lisbeth M
authors.initials: LM
authors.lastname: Baggesen
authors.affiliation: Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren P
authors.initials: SP
authors.lastname: Johnsen
authors.affiliation: Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Helene
authors.initials: H
authors.lastname: Nørrelund
authors.affiliation: Novo Nordisk Scandinavia AB, Ørestad, Copenhagen, Denmark.
authors.forename: Esben S
authors.initials: ES
authors.lastname: Buhl
authors.affiliation: Novo Nordisk Scandinavia AB, Ørestad, Copenhagen, Denmark.
authors.forename: Christiane L
authors.initials: CL
authors.lastname: Haase
authors.affiliation: Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark rwt@clin.au.dk.
authors.forename: Reimar W
authors.identifier: 0000-0001-9135-3474
authors.initials: RW
authors.lastname: Thomsen
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin