Observational studyJournal of diabetes investigation2022

Real-world risk of lower-limb amputation associated with sodium-glucose cotransporter 2 inhibitors versus metformin: A propensity score-matched model analysis in Japan.

Gen Mizutani, Takeshi Horii, Yoichi Oikawa, Koichiro Atsuda, Akira Shimada

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Journal of diabetes investigation, 2022. The graph read 3 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports 2 associations that do not count as treatment evidence, such as HR 2.68 (1.18 to 8.20) for risk of amputation. Cited by 3 papers, 1 of them a synthesis that pooled it.

3numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 31% 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.

Read, but not usablea number the graph found but could not read as for or against

Risk of amputationSGLT2is vs metformin, in use of strong statinsan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 2.681.18 to 8.20
However, female sex (HR 2.78, 95% CI 1.12-6.94) and use of strong statins (HR 2.68; 95% CI 1.18-8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group.
Risk of amputationSGLT2is vs metformin, in female sexan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 2.781.12 to 6.94
However, female sex (HR 2.78, 95% CI 1.12-6.94) and use of strong statins (HR 2.68; 95% CI 1.18-8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group.
Risk of amputationSGLT2is vs metforminan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 1.340.80 to 2.24
There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80-2.24).

The authors add: There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80-2.24).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

SGLT2 inhibitors×cardiovascular events

No readable resultOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 11 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT0493781616,746 enrolled · 2021
HR 1.000.83 to 1.20
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
NCT045647424,017 enrolled · 2020
Win Ratio (WR) 1.341.20 to 1.50
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

5 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Gen Mizutani *Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan.
Takeshi Horii *Research and Education Center for Clinical Pharmacy, Division of Clinical Pharmacy, Laboratory of Pharmacy Practice and Science 1, 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 AtsudaResearch and Education Center for Clinical Pharmacy, Division of Clinical Pharmacy, Laboratory of Pharmacy Practice and Science 1, Kitasato University School of Pharmacy, Kanagawa, Japan.
Akira ShimadaDepartment of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan.
Saitama Medical University · JPKitasato University · JPMusashino University · JP

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

AIMS/

introductionWe aimed to clarify the real-world risk of lower-limb amputation and identify factors related to increased risk in Japanese patients with type 2 diabetes using sodium-glucose cotransporter 2 inhibitors (SGLT2is). MATERIALS AND

methodsWe carried out a retrospective observational cohort study utilizing the Japanese Medical Data Vision, a diagnosis procedure combination database. We identified 107,296 patients with type 2 diabetes who were initiated on SGLT2is or metformin (control; n = 53,648 per group) using 1:1 propensity score matching from April 2014 to October 2019. The hazard ratio (HR) for the risk of lower-limb amputation was analyzed using a Cox proportional hazards model adjusted for patients' baseline characteristics and use of concomitant medical agents.

resultsOf the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80-2.24). However, female sex (HR 2.78, 95% CI 1.12-6.94) and use of strong statins (HR 2.68; 95% CI 1.18-8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group.

conclusionsSGLT2is might not be related to an increased risk of lower-limb amputation in patients with type 2 diabetes in real-world clinical practice. The possible increased risk of SGLT2is-associated amputation in female patients with type 2 diabetes and patients with type 2 diabetes requiring strong statins is notable.

Indexed as

Diabetes Mellitus, Type 2Hydroxymethylglutaryl-CoA Reductase InhibitorsMetforminSodium-Glucose Transporter 2 InhibitorsAmputation, SurgicalFemaleGlucoseHumansHypoglycemic AgentsJapanPropensity ScoreRetrospective StudiesSodiumGlucoseHydroxymethylglutaryl-CoA Reductase InhibitorsHypoglycemic AgentsMetforminSodiumSodium-Glucose Transporter 2 InhibitorsLower-limb amputationSodium-glucose cotransporter 2 inhibitorType 2 diabetes

Identifiers

PMID36124433
PMCPMC9720178
OpenAlexW4296782468

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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.