Evidence mapPaperPMID 41196845Full record

ArticlePloS one2025

Comparative effectiveness of biguanides versus SGLT2 inhibitors on cardiovascular and cerebrovascular events, diabetic nephropathy, retinopathy, neuropathy, and treatment expenditures in patients with type 2 diabetes.

Eiji Nakatani, Hiromitsu Ohno, Takayoshi Nagahama, Toru Tonoike, Hiromichi Yui, Tatsunori Satoh, Taku Matsunaga, Daito Funaki, Chikara Ueki, Emi Ohata and 6 more

Abstract readComparative Study
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

1 citing paper in PubMed.

  1. Structural Characterisation ofMolecules (Basel, Switzerland) · 2026
    Article
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

16 authors.

Eiji NakataniGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.ORCID https://orcid.org/0000-0002-4876-446X
Hiromitsu OhnoAllied Medical K.K., Tokyo, Japan.
Takayoshi NagahamaAllied Medical K.K., Tokyo, Japan.
Toru TonoikeAllied Medical K.K., Tokyo, Japan.
Hiromichi YuiAllied Medical K.K., Tokyo, Japan.
Tatsunori SatohGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Taku MatsunagaGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Daito FunakiGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Chikara UekiGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Emi OhataGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Akinori MiyakoshiGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Ataru IgarashiGraduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Yoshihiro TanakaGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
Hideaki KanedaOkinaka Memorial Institute for Medical Research, Tokyo, Japan.
Hiraku KumamaruDepartment of Health Data Science, Graduate School of Data Science Yokohama City University, Yokohama, Japan.
Akira SugawaraGraduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly recommended as first-line treatment for type 2 diabetes mellitus (T2DM), but head-to-head data comparing them with metformin, the canonical biguanide, remain sparse in Japan.

objectiveTo compare the long-term effectiveness and cost of initiating treatment with a biguanide versus an SGLT2 inhibitor, excluding the alternative class for 12 months but permitting other antidiabetic drugs, on a composite of major cardio-cerebrovascular events and all-cause death, and a composite of diabetic complications.

methodsWe emulated a new-user cohort trial using the Shizuoka Kokuho Database (2014-2021). Patients initiating treatment with either a biguanide or an SGLT2 inhibitor, while avoiding the alternative class during the first 12 months but allowing other glucose-lowering agents, were included. Follow-up began at treatment initiation; those who received the comparator drug within 12 months were excluded. After 1:1 propensity-score matching on demographic, clinical, laboratory, and lifestyle variables, cause-specific Cox models estimated hazard ratios (HRs). Daily medication costs were compared.

resultsAfter matching, 1,246 patients (623 per group) were followed for a median of 2.9 years (maximum 7.2 years). Cardio-cerebrovascular composite: 44/623 biguanide users (7.1%) and 35/623 SGLT2 inhibitor users (5.6%) experienced a first event (HR 0.80, 95% CI 0.51-1.24). Diabetic complications: 86/623 (13.8%) vs. 78/623 (12.5%) (HR 0.88, 95% CI 0.70-1.13). Median daily drug cost was 124.7 JPY for biguanides and 184.0 JPY for SGLT2 inhibitors (P < 0.001).

conclusionUsing a large-scale regional database from Japan, we found that among adults with type 2 diabetes without prior major cardiac or renal disease, first-line treatment with an SGLT2 inhibitor did not reduce risks of cardio-cerebrovascular events, mortality, or complications compared with metformin, and cost about 50% more.

Indexed as

BiguanidesCardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesDiabetic NeuropathiesDiabetic RetinopathyHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsAgedCerebrovascular DisordersFemaleHumansJapanMaleMetforminMiddle AgedBiguanidesHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID41196845
PMCPMC12591428

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.