Trial reportCardiovascular diabetology2021

Comparison of the clinical effect of empagliflozin on glycemic and non-glycemic parameters in Japanese patients with type 2 diabetes and cardiovascular disease treated with or without baseline metformin.

Atsushi Tanaka, Michio Shimabukuro, Hiroki Teragawa, Yosuke Okada, Toshinari Takamura, Isao Taguchi, Shigeru Toyoda, Hirofumi Tomiyama, Shinichiro Ueda, Yukihito Higashi and 2 more

Open access · goldFull text readComparative StudyMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2021. The graph read 2 numbers from its abstract, feeding 4 cells of the map, but none could be read as for or against, so it casts no vote. It also reports an association that does not count as treatment evidence, such as difference -0.54 (-1.07 to -0.01) for Reduction in body mass index (BMI). Cited by 6 papers.

2numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

Decrease in systolic blood pressure from baseline levelsbaseline metformin use (within empagliflozin arm) vs metformin-naïve patients (within empagliflozin arm), in patients treated with empagliflozinan association or prognostic statement, not a treatment comparison · ascvd, t2dfeeds 2 cells of the map
Δ -8.50-17.7 to 0.60As written: p = 0.066
In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the decrease in systolic blood pressure from baseline levels was greater in patients receiving metformin, compared to that observed in metformin-naïve patients (group difference - 8.5 [95% confidence interval (CI) - 17.7 to 0.6 mmHg], p = 0.066).
Reduction in body mass index (BMI)baseline metformin use (within empagliflozin arm) vs nonusers of baseline metformin (within empagliflozin arm), in patients treated with empagliflozinan association or prognostic statement, not a treatment comparison · ascvd, t2dfeeds 2 cells of the map
Δ -0.54-1.07 to -0.01
Reduction in body mass index (BMI) was significantly greater in patients receiving baseline metformin, relative to nonusers (- 0.54 [95% CI - 1.07 to - 0.01] kg/m CONCLUSION: Our findings suggest 24 weeks of empagliflozin treatment was associated with an improvement in glycemic control, irrespective of the baseline use of metformin therapy.

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.

Metformin×blood pressure

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

6 readable studies in this cell: 2 favour the treatment, 3 find no difference, 1 favour the comparator.

Belief with this paper
0.40contested · 1 family supports, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect

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

Metformin×body weight & composition

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

19 readable studies in this cell: 7 favour the treatment, 6 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 8 families support, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT018093271,186 enrolled · 2013
Δ -0.90-1.60 to -0.20
NCT008598981,093 enrolled · 2009
Δ -1.37-2.03 to -0.71
NCT00643851994 enrolled · 2008
Δ -0.05-0.72 to 0.61
NCT02932475831 enrolled · 2017
Δ 0.04
NCT00676338820 enrolled · 2008
Δ -0.04-0.61 to 0.53
NCT02980276535 enrolled · 2017
Δ -0.70-1.30 to -0.20
Δ 17.05.00 to 29.0
increase 1.26-0.24 to 2.75
weight loss -16.2-60.2 to -4.40

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

SGLT2 inhibitors×blood pressure

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

38 readable studies in this cell: 24 favour the treatment, 14 find no difference, 0 favour the comparator.

Belief with this paper
0.88established · 14 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ -2.96-4.00 to -1.91
NCT011374742,996 enrolled · 2010
Δ -3.05-4.87 to -1.24
NCT011956622,245 enrolled · 2010
Δ -4.28-6.54 to -2.02
NCT011066771,284 enrolled · 2010
Δ -2.87-4.46 to -1.28
NCT020991101,233 enrolled · 2014
Δ -2.76-4.69 to -0.83
NCT018093271,186 enrolled · 2013
Δ -1.91-3.64 to -0.18
NCT02580591977 enrolled · 2015
Δ -2.10-3.90 to -0.20
NCT01042977964 enrolled · 2010
Δ -2.71-4.28 to -1.15
NCT03332771954 enrolled · 2017
Δ -4.18-6.70 to -1.65
NCT00984867833 enrolled · 2009
Δ -0.86-3.75 to 2.03
NCT03351478770 enrolled · 2017
Δ -2.05-4.87 to 0.76
NCT01137812756 enrolled · 2010
Δ -5.91-7.64 to -4.17

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

SGLT2 inhibitors×body weight & composition

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

40 readable studies in this cell: 62 favour the treatment, 9 find no difference, 2 favour the comparator.

Belief with this paper
0.98established · 50 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ -2.96-3.47 to -2.45
NCT010956661,484 enrolled · 2010
Δ -1.10-1.65 to -0.56
NCT009688121,452 enrolled · 2009
Δ -5.20-5.70 to -4.70
NCT017190031,413 enrolled · 2012
Adjusted mean -2.50-3.33 to -1.68
NCT011066771,284 enrolled · 2010
Δ -2.40-3.00 to -1.80
NCT016060071,282 enrolled · 2012
Δ -2.05-2.73 to -1.37
NCT006732311,240 enrolled · 2008
Δ -1.00-1.50 to -0.49
NCT020991101,233 enrolled · 2014
Δ -1.85-2.48 to -1.22
NCT006609071,217 enrolled · 2008
Δ -4.65-5.14 to -4.17
NCT018093271,186 enrolled · 2013
Δ -0.90-1.60 to -0.20
NCT010956531,179 enrolled · 2010
Δ -1.37-2.01 to -0.73
NCT008598981,093 enrolled · 2009
Δ -1.97-2.64 to -1.30

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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Article
  3. Observational
  4. The Role of Diabetes and SGLT2 Inhibitors in Cerebrovascular Diseases.Current neurology and neuroscience reports · 2025
    Review
  5. Article
  6. Review
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

12 authors at 10 institutions in 1 country.

Atsushi TanakaDepartment of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. tanakaa2@cc.saga-u.ac.jp.ORCID 0000-0003-3352-7661
Michio ShimabukuroDepartment of Diabetes, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Hiroki TeragawaDepartment of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan.
Yosuke OkadaFirst Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyusyu, Japan.
Toshinari TakamuraDepartment of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Isao TaguchiDepartment of Cardiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan.
Shigeru ToyodaDepartment of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Japan.
Hirofumi TomiyamaDepartment of Cardiology, Tokyo Medical University, Tokyo, Japan.
Shinichiro UedaDepartment of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan.
Yukihito HigashiDepartment of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Koichi NodeDepartment of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. node@c.saga-u.ac.jp.
EMBLEM Investigators
Saga University · JPDokkyo Medical University · JPDokkyo Medical University Saitama Medical Center · JPFukushima Medical University · JPHiroshima General Hospital · JPHiroshima University · JPKanazawa University · JPTokyo Medical University · JPUniversity of Occupational and Environmental Health Japan · JPUniversity of the Ryukyus · 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.

backgroundThe most recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors should be considered preferentially in patients with T2D with either a high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of conventional metformin therapy. Whether the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin therapy however remains unclear.

methodsThe study was a post hoc analysis of the EMBLEM trial (UMIN000024502). All participants (n = 105; women 31.4%; mean age 64.8 years) had both T2D and CVD and were randomized to either 24 weeks of empagliflozin 10 mg daily or placebo. Analysis of the data assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin.

resultsOverall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the decrease in systolic blood pressure from baseline levels was greater in patients receiving metformin, compared to that observed in metformin-naïve patients (group difference - 8.5 [95% confidence interval (CI) - 17.7 to 0.6 mmHg], p = 0.066). Reduction in body mass index (BMI) was significantly greater in patients receiving baseline metformin, relative to nonusers (- 0.54 [95% CI - 1.07 to - 0.01] kg/m

conclusionOur findings suggest 24 weeks of empagliflozin treatment was associated with an improvement in glycemic control, irrespective of the baseline use of metformin therapy. The effects of empagliflozin on reductions in BMI and hs-TnI were more apparent in patients who received baseline metformin therapy, compared to that observed in metformin-naïve patients. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502.

Indexed as

Glycemic ControlAgedBenzhydryl CompoundsBiomarkersBlood GlucoseCardiovascular DiseasesDiabetes Mellitus, Type 2Double-Blind MethodFemaleGlucosidesGlycated HemoglobinHumansJapanMaleMetforminMiddle AgedBenzhydryl CompoundsBiomarkersBlood GlucoseempagliflozinGlucosidesGlycated Hemoglobinhemoglobin A1c protein, humanMetforminSodium-Glucose Transporter 2 InhibitorsCardiovascular diseaseMetforminSodium-glucose cotransporter 2 inhibitorType 2 diabetes

Identifiers

PMID34332584
PMCPMC8325864
OpenAlexW3191681009

What Socratic holds

Textfull text, public
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.