Comparison of the effects on cardiovascular events between use of metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycaemic agents in Japanese patients with type 2 diabetes mellitus: a claims database analysis.

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  • Additional Information
    • Source:
      Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BMJ Publishing Group Ltd, 2011-
    • Subject Terms:
      Diabetes Mellitus, Type 2*/chemically induced ; Diabetes Mellitus, Type 2*/drug therapy ; Dipeptidyl-Peptidase IV Inhibitors*/adverse effects ; Metformin*/therapeutic use ; Myocardial Infarction*/drug therapy; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use ; Glycated Hemoglobin/analysis ; Humans ; Hypoglycemic Agents/therapeutic use ; Japan ; Retrospective Studies
    • Abstract:
      Objectives: To compare the risk of cardiovascular events from the initiation of therapy between metformin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as first-line therapy.
      Design: Retrospective cohort study using two claims databases.
      Setting: The MDV database (provided by Medical Data Vision) comprised data from acute care hospitals, and the JMDC database (provided by JMDC) comprised data from individuals covered by health insurance societies.
      Participants: Those who were diagnosed with type 2 diabetes at ≥18 years, prescribed metformin or DPP-4i as the first-line hypoglycaemic agent, had medical records of ≥6 months before the index prescription and had available glycated haemoglobin (HbA1c) data for the period, including the index date and 30 days before it (defined as the baseline) were included. Those diagnosed with type 1 diabetes and/or a history of myocardial infarction (MI) or cerebrovascular diseases were excluded.
      Primary and Secondary Outcome Measures: The outcomes were cumulative risks from Kaplan-Meier curves or HRs of patients prescribed metformin compared with DPP-4i. The primary endpoint was the diagnosis of MI or stroke associated with hospitalisation. Patient demographics, prescribed drugs and laboratory test values of HbA1c and estimated glomerular filtration rate at baseline were adjusted. The study period starting from the index included treatment after initial monotherapy.
      Results: Overall, 2089 and 6686 patients in the MDV database and 1506 and 3635 in the JMDC database were prescribed metformin and DPP-4i, respectively. The HR of the primary endpoint was 0.879 with no statistical significance (95% CI 0.534 to 1.448, p=0.613) in the MDV database, while it was significantly lower, 0.398 (95% CI 0.213 to 0.742, 0.004) in the JMDC database.
      Conclusions: Patients who received metformin as first-line therapy may have reduced cardiovascular events than those receiving DPP-4i. This study conforms to previous Japanese database studies, despite the consideration of its limitation being an observational design.
      Competing Interests: Competing interests: RN has received honoraria from Astellas Pharma Inc., Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Medtronic Japan Co., Ltd, MSD, Novartis Pharma K.K., Novo Nordisk Pharma Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd. He has also received a grant from the Japan Diabetes Foundation and Nippon Boehringer Ingelheim Co., Ltd. TT and KI are employees of Milliman Inc., which has received consultancy fees from Sumitomo Dainippon Pharma Co., Ltd. SA is employee of Sumitomo Dainippon Pharma Co., Ltd.
      (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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    • Contributed Indexing:
      Keywords: diabetes & endocrinology; diabetic nephropathy & vascular disease
    • Accession Number:
      0 (Dipeptidyl-Peptidase IV Inhibitors)
      0 (Glycated Hemoglobin A)
      0 (Hypoglycemic Agents)
      9100L32L2N (Metformin)
      EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases)
    • Publication Date:
      Date Created: 20220312 Date Completed: 20220427 Latest Revision: 20221207
    • Publication Date:
      20231215
    • Accession Number:
      PMC8919442
    • Accession Number:
      10.1136/bmjopen-2020-045966
    • Accession Number:
      35277396