title: Impact of hypoglycemic events and HbA1c level on sulfonylurea discontinuation and down-titration.
abstract: BACKGROUND
  A retrospective cohort study using GE Centricity electronic medical records assessed the association between post-index hypoglycemia and HbA1c with discontinuation and down-titration of sulfonylureas among patients with Type 2 diabetes mellitus.
  
  
  METHODS
  Adult patients with an index prescription for a sulfonylurea and ≥12 months' continuous records pre- and post-index were eligible. Sulfonylurea discontinuation and down-titration was assessed 1-year post-index. Discontinuation occurred if the date of a prescription was >90 days from the preceding prescription plus days of supply. Down-titration occurred when a subsequent prescription was lower than the index dose. Cox regression assessed the association between post-index hypoglycemia and HbA1c with time to sulfonylurea discontinuation and down-titration, as well as other factors.
  
  
  RESULTS
  28,371 participants were included in the study; 13,459 (47.4%) were discontinuers, 717 (2.5%) were down-titraters, and 14,195 (50.0%) were continuers. 0.6% of continuers experienced hypoglycemia 1-year post-index, compared with 3.1% of down-titraters and 0.8% of discontinuers (p < 0.0001). Patients with post-index hypoglycemia had a significantly higher rate of discontinuation (hazard ratio [HR] = 1.82, 95% CI: 1.47-2.23) and down-titration (HR = 4.25, 95% CI: 1.92-8.03). Patients with higher post-index HbA1c and use of 2ndgeneration sulfonylureas had an increased rate of discontinuation (HR = 1.05, 95% CI: 1.04-1.06; HR = 1.19, 95% CI: 1.14-1.24, respectively).
  
  
  CONCLUSIONS
  Approximately half of participants who initiated sulfonylureas discontinued or down-titrated therapy within one year. Both post-index hypoglycemia and higher HbA1c were significant risk factors for sulfonylurea treatment change.
authors.affiliation: a Outcomes Research , MSD Portugal , Paço de Arcos , Portugal.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Laires
authors.affiliation: b Asclepius Analytics Ltd , Wan Chai , Hong Kong.
authors.forename: Jackson
authors.initials: J
authors.lastname: Tang
authors.affiliation: b Asclepius Analytics Ltd , Wan Chai , Hong Kong.
authors.forename: Chun Po Steve
authors.initials: CP
authors.lastname: Fan
authors.affiliation: b Asclepius Analytics Ltd , Wan Chai , Hong Kong.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: c Center for Observational and Real-world Evidence , Merck & Co., Inc ., Kenilworth , NJ , USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: c Center for Observational and Real-world Evidence , Merck & Co., Inc ., Kenilworth , NJ , USA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Iglay
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds
keywords: Type 2 diabetes; glycemic control; hypoglycemia; persistence study; sulfonylureas; therapy discontinuation; therapy down-titration; treatment patterns