Evidence map›Paper›PMID 33448127›Full record

Observational studyJournal of diabetes investigation2021

On-label use of sodium-glucose cotransporter 2 inhibitors might increase the risk of diabetic ketoacidosis in patients with type 1 diabetes.

Takeshi Horii, Yoichi Oikawa, Koichiro Atsuda, Akira Shimada

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Journal of diabetes investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Euglycemic Diabetic Ketoacidosis: Clinical Suspicion and Diagnosis.Clinical medicine insights. Endocrinology and diabetes · 2026
    Review
  6. Article
  7. Update on slowly progressive type 1 diabetes.Journal of diabetes investigation · 2025
    Article
  8. Update on Measuring Ketones.Journal of diabetes science and technology · 2024
    Review
  9. Article
  10. Article
  11. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Takeshi HoriiLaboratory of Pharmacy Practice and Science 1, Division of Clinical Pharmacy, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Kanagawa, Japan.ORCID https://orcid.org/0000-0002-5465-4531
Yoichi OikawaDepartment of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan.ORCID https://orcid.org/0000-0003-1524-6751
Koichiro AtsudaLaboratory of Pharmacy Practice and Science 1, Division of Clinical Pharmacy, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Kanagawa, Japan.
Akira ShimadaDepartment of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan.ORCID https://orcid.org/0000-0002-3954-4983
Kitasato University · JPSaitama Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

AIMS/

introductionThis study aimed to investigate the risk of diabetic ketoacidosis (DKA) in insulin-treated type 1 diabetes patients administered sodium-glucose cotransporter 2 (SGLT2) inhibitors in real-world clinical practice. MATERIALS AND

methodsWe carried out a real-world, retrospective, observational cohort study using Japanese Medical Data Vision, a diagnosis procedure combination database. We identified insulin-treated adult type 1 diabetes patients enrolled from December 2018 to October 2019. We assessed the incidence and risk of DKA in type 1 diabetes patients using SGLT2 inhibitors in an 'on-label' manner. Cox multivariate regression analyses were carried out to determine clinical factors linked to SGLT2 inhibitor-associated DKA.

resultsOf 11,475 type 1 diabetes patients, 1,898 (16.5%) were prescribed SGLT2 inhibitors. DKA occurred in 139 (7.3%) of these patients, with 20.2 incidences per 100 person-years. These patients also showed significantly higher DKA rates than did those not receiving SGLT2 inhibitors (hazard ratio 1.66, 95% confidence interval 1.33-2.06; P < 0.001). The mean time until DKA onset in SGLT2 inhibitor-treated type 1 diabetes patients was 30.6 ± 30.1 days. The risk of SGLT2 inhibitor-associated DKA increased in type 1 diabetes patients irrespective of sex, age or body mass index. However, the risk did not increase in type 1 diabetes patients receiving continuous subcutaneous insulin infusion, which warrants further investigation because of the small number of type 1 diabetes patients receiving continuous subcutaneous insulin infusion.

conclusions'On-label' SGLT2 inhibitor use might increase DKA risk among insulin-treated type 1 diabetes patients irrespective of sex, age or body mass index. Both type 1 diabetes patients and healthcare providers should be wary of DKA, especially during the first month of initiating SGLT2 inhibitors.

Indexed as

AdultAgedBiomarkersBlood GlucoseDiabetes Mellitus, Type 1Diabetic KetoacidosisFemaleFollow-Up StudiesHumansIncidenceJapanMaleMiddle AgedPrognosisRetrospective StudiesSodium-Glucose Transporter 2 InhibitorsBiomarkersBlood GlucoseSodium-Glucose Transporter 2 InhibitorsDiabetic ketoacidosisSodium-glucose cotransporter 2 inhibitorType 1 diabetes

Identifiers

PMID33448127
PMCPMC8409873
OpenAlexW3122056458

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.