title: Impact of the sitagliptin alert on prescription of oral antihyperglycemic drugs in Japan.
abstract: BACKGROUND
  Sitagliptin, the first of a new class of dipeptidyl peptidase-4 (DPP-4)-inhibitory oral antihyperglycemic drugs (OHDs), was introduced in Japan in December 2009. In April 2010 a safety alert was issued regarding the risk of serious hypoglycemic events when the drug is used in combination with high-dose sulfonylureas (SUs).
  
  
  OBJECTIVE
  To investigate trends in prescription of OHDs before and after the launch of sitagliptin, and before and after the safety alert, in order to evaluate changes in the prescribing behavior of various groups of physicians in response to the safety alert.
  
  
  METHODS
  Japan.
  
  
  METHODS
  Prescription data from 6,500 institutions, randomly collected from 300 Japanese pharmacies were used. A cohort of 87,678 patients with 813,374 prescriptions for OHDs, among which 464,079 included SUs (glimepiride: 317,423), was collected from August 2009 to 31 December 2010. Logistic regression analysis was conducted.
  
  
  METHODS
  Prescription trends for sitagliptin and SUs, stratified by age, gender, types of prescribers and institutions.
  
  
  RESULTS
  The safety alert recommending a reduction of SU dosing was well reflected in prescriptions issued after the alert (glimepiride dose reduction from 2.78 ± 1.86 mg to 2.32 ± 1.68), especially in prescriptions issued by diabetes specialists (from 2.27 ± 1.81 mg to 1.87 ± 1.47 mg). The dose of background SUs in patients who started sitagliptin early was higher (before alert: 2.70 ± 1.80 mg, after alert: 2.51 ± 1.74 mg) than in patients without experience of sitagliptin (2.12 ± 1.57 mg). This may indicate that patients receiving high-dose SUs were selected for sitagliptin, and this might be a factor in the high frequency of hypoglycemia in the early launch phase of sitagliptin.
  
  
  CONCLUSIONS
  The sitagliptin safety alert had a clear impact on prescribing behavior, but the impact appeared to depend on prescribers' backgrounds. Our findings should be helpful for developing a safer drug launching strategy for new classes of drugs in established categories.
authors.affiliation: Pharmaco-Business Innovation Laboratory, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. vyb00665@nifty.com
authors.forename: Daisaku
authors.initials: D
authors.lastname: Sato
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Sachiko
authors.initials: S
authors.lastname: Masuda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000284:Administration, Oral; D016907:Adverse Drug Reaction Reporting Systems / Q000639:trends*; D000368:Aged; D016009:Chi-Square Distribution; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects*; D011307:Drug Prescriptions; D004363:Drug Utilization / Q000639:trends; D017723:Drug Utilization Review; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010818:Practice Patterns, Physicians' / Q000639:trends*; D011719:Pyrazines / Q000009:adverse effects*; D012189:Retrospective Studies; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D013997:Time Factors; D014230:Triazoles / Q000009:adverse effects*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D013453:Sulfonylurea Compounds; D014230:Triazoles; D000068900:Sitagliptin Phosphate