Impact of the sitagliptin alert on prescription of oral antihyperglycemic drugs in Japan
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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. Setting Japan. Method 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. Main Outcome Measure 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. Conclusion 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.
KeywordsDipeptidyl peptidase-4 (DPP-4)-inhibitor Hypoglycemia events Japan Prescribing behavior Retrospective cohort study Safety alert
The author wishes to acknowledge the help of the Japan Medical Information Research Institute Inc. (JMIRI) for data collection and Dr. Hirotsugu Suwanai, Diabetes and Metabolic Medicine, Faculty of Medicine, the University of Tokyo, for medical advice.
Conflicts of interest
Mr. Sato and Dr. Sato declare no conflict of interest. Dr. Kimura and Dr. Masuda are employed by the University of Tokyo with endowment funding from several companies, including Daiichi Sankyo Co., Ltd. and Chugai Pharmaceutical Co., Ltd.
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