{
  "abstract": "Objectives: In recent years, with the considerable changes in the therapeutic armamentarium for diabetes, the incidence of hypoglycemia events, especially severe hypoglycemia events, associated with drug treatment in people with diabetes has markedly decreased. We were prompted to evaluate the threshold for each intervention target, especially glycemic control, associated with a minimized risk of the macrovascular complications of diabetes in this setting. Methods: In the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3) conducted by us previously, we recruited 2542 participants and assigned them to a conventional therapy group (n = 1271) and an intensive therapy group (n = 1271; two ineligible participants were removed from all analyses afterwards), and the incidence of severe hypoglycemia events was low in both groups (7 in the intensive therapy group and 4 in the conventional therapy group during a median 8.5 years’ follow-up). Towards the objective of this study, we undertook a landmark analysis with a landmark time-point of 1 year after the baseline of the J-DOIT3 study. Then, using the updated mean values of the glycated hemoglobin (HbA1c), systolic blood pressure, and LDL-cholesterol and HDL-cholesterol levels, we determined the optimal levels of each of these variables associated with the lowest hazard ratios for outcomes, including the primary and cardiovascular outcomes. Results: For glycemic control, our results revealed no clear lower threshold of the glycated hemoglobin associated with the lowest risk of myocardial infarction or all-cause mortality; for other risk factors, it might be an important treatment target to maintain the LDL-cholesterol levels at below 80 mg/dL to minimize the risk of stroke. Conclusions: The present analysis suggested that the treatment target for HbA1c to minimize the risk of all-cause mortality in participants with diabetes with a low incidence of severe hypoglycemia episodes could be < 6.5% (ClinicalTrials.gov, number NCT00300976).",
  "abstract_shown": true,
  "affiliations": [
    "Department of Diabetes, Metabolism and Endocrinology, Ichikawa Medical Center, International University of Health and Welfare, Chiba, Japan.",
    "Department of Endocrinology and Diabetes, Saitama Medical University, Saitama, Japan.",
    "Diabetes Research Center, Japan Institute for Health Security, Tokyo, Japan.",
    "Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.",
    "Okachimachi Ohisama Clinic, Tokyo, Japan.",
    "Center for Digital Transformation for Health, Kyoto University School of Medicine, Kyoto, Japan.",
    "Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.",
    "Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.",
    "Toranomon Hospital, Tokyo, Japan."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mitsuhiko Noda",
      "orcid": "0000-0003-0413-4631"
    },
    {
      "affs": [
        2
      ],
      "name": "Kohjiro Ueki"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "Takayoshi Sasako",
      "orcid": "0000-0002-7644-309X"
    },
    {
      "affs": [
        5
      ],
      "name": "Naoki Ishizuka"
    },
    {
      "affs": [
        3
      ],
      "name": "Kana Miyake"
    },
    {
      "affs": [
        3
      ],
      "name": "Kengo Miyoshi"
    },
    {
      "affs": [
        3
      ],
      "name": "Tomohisa Aoyama"
    },
    {
      "affs": [
        6
      ],
      "name": "Yukiko Okazaki"
    },
    {
      "affs": [
        7
      ],
      "name": "Yasuo Ohashi"
    },
    {
      "affs": [
        3
      ],
      "name": "Toshimasa Yamauchi"
    },
    {
      "affs": [
        3,
        8
      ],
      "name": "Takashi Kadowaki"
    },
    {
      "name": "J-DOIT3 Study Group"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cpf2a24zyzhhy.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0360295",
  "fulltext_url": "https://europepmc.org/articles/PMC13693898",
  "id": "cpf2a24zyzhhy",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0360295",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2712|Diabetes Treatment and Management"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Hemoglobin/HbA1c"
    ],
    [
      "plos",
      "/Biology and life sciences/Population biology/Population metrics/Death rates"
    ],
    [
      "plos",
      "/Medicine and health sciences/Cardiology/Cardiovascular medicine/Cardiovascular diseases/Cardiovascular disease risk"
    ],
    [
      "plos",
      "/Medicine and health sciences/Cardiology/Myocardial infarction"
    ],
    [
      "plos",
      "/Medicine and health sciences/Diagnostic medicine/Diabetes diagnosis and management/HbA1c"
    ],
    [
      "plos",
      "/Medicine and health sciences/Endocrinology/Endocrine disorders/Diabetes mellitus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Cardiovascular diseases/Cardiovascular disease risk"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Cerebrovascular diseases/Stroke"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Metabolic disorders/Diabetes mellitus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Metabolic disorders/Hypoglycemia"
    ],
    [
      "plos",
      "/Medicine and health sciences/Neurology/Cerebrovascular diseases/Stroke"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmaceutics/Drug therapy/Cardiovascular therapy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Vascular medicine/Stroke"
    ]
  ],
  "openalex": "W7223375463",
  "pdf_url": "https://europepmc.org/articles/PMC13693898?pdf=render",
  "pmcid": "PMC13693898",
  "pmid": "42912779",
  "published": "2026-10-23",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/cpf2a24zyzhhy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
      "native_id": "10.1371/journal.pone.0360295",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0360295"
    },
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42912779",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42912779"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:cardiovascular diseases",
      "subfield": "cardiovascular"
    },
    {
      "field": "medicine",
      "origin": "plos:endocrinology",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Search for the glycated hemoglobin target minimizing mortality among people with type 2 diabetes with rare incidence of treatment-related severe hypoglycemia – Epidemiologic analysis of J-DOIT3 randomized controlled trial",
  "title_text": "Search for the glycated hemoglobin target minimizing mortality among people with type 2 diabetes with rare incidence of treatment-related severe hypoglycemia – Epidemiologic analysis of J-DOIT3 randomized controlled trial",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/cpf2a24zyzhhy",
  "venue": "PLOS One",
  "versions": []
}