title: Effects of randomization to intensive glucose control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the ACCORD Trial.
abstract: OBJECTIVE
  We explore the effect of randomized treatment, comparing intensive to standard glucose-lowering strategies on major cardiovascular outcomes, death, and severe adverse events in older versus younger participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
  
  
  METHODS
  Participants with type 2 diabetes (n = 10,251) with a mean age of 62 years, a median duration of diabetes of 10 years, and a median A1C of 8.1% (65 mmol/mol) were randomized to treatment strategies targeting either A1C <6.0% (42 mmol/mol) or 7.0-7.9% (53-63 mmol/mol) and followed for a mean of 3.7 years. Outcomes were analyzed within subgroups defined by baseline age (<65 vs. ≥65 years).
  
  
  RESULTS
  Older and younger ACCORD participants achieved similar intensive-arm A1C levels and between-arm A1C differences. Within the older subgroup, similar hazards of the cardiovascular primary outcome and total mortality were observed in the two arms. While there was no intervention effect on cardiovascular mortality in the older subgroup, there was an increased risk in the intensive arm for the younger subgroup (older hazard ratio [HR] = 0.97; younger HR = 1.71; P = 0.03). Regardless of intervention arm, the older subgroup experienced higher annualized rates of severe hypoglycemia (4.45% intensive and 1.36% standard) than the younger subgroup (2.45% intensive and 0.80% standard).
  
  
  CONCLUSIONS
  Intensive glucose lowering increased the risk of cardiovascular disease and total mortality in younger participants, whereas it had a neutral effect in older participants. The intensive to standard relative risk of severe hypoglycemia was similar in both age subgroups, with higher absolute rates in older participants within both treatment arms.
authors.affiliation: Corresponding author: Michael E. Miller, mmiller@wakehealth.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Miller
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Robert P
authors.initials: RP
authors.lastname: Byington
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.forename: Walter T
authors.initials: WT
authors.lastname: Ambrosius
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: William B
authors.initials: WB
authors.lastname: Applegate
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000401:mortality; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents