Evidence map›Paper›PMID 32358544›Full record

ArticleNature communications2020

SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease.

So Ra Kim, Sang-Guk Lee, Soo Hyun Kim, Jin Hee Kim, Eunhye Choi, Wonhee Cho, John Hoon Rim, Inhwa Hwang, Chan Joo Lee, Minyoung Lee and 12 more

5 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 337 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
337citing papers in PubMed, 4 pooled it
21.9field-weighted citation impact, top 1% 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.

NCT05194592 phase4unknown statusstarted 2022, after this paper: background citation

Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes

Ran2022Enrolled122Registered outcomes4Posted comparisons0ConditionsRemodeling, Ventricular, Type2 DiabetesArmsdapagliflozin, Gemigliptin
Open the trial in the graph
NCT05330013 phase2withdrawnstarted 2022, after this paper: background citation

Pilot Study to Evaluate the Effect of Inflammation in Heart Failure

Ran2022Enrolled0Registered outcomes3Posted comparisons0ConditionsHeart Failure, Inflammation, Myocardial DysfunctionArmsCMR imaging, dapagliflozin, MRI scan
PMID 34449189PMID 32578850other papers from this trial
Open the trial in the graph
NCT05975528 phase4unknown statusstarted 2023, after this paper: background citation

Effect of Sodium-glucose Cotransporter-2 Inhibitor in Cellular Senescence in Patients With Cardiovascular Diseases or Advanced Type 2 Diabetes

Ran2023Enrolled92Registered outcomes14Posted comparisons0ConditionsCellular Senescence, Diabetes Mellitus, Sodium-Glucose Transporter 2 InhibitorsArmsGlimepiride, SGLT2 inhibitor
Open the trial in the graph
NCT05512130 early_phase1unknown statusnot on this mapstarted 2022, after this paper: background citation

Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy

TypeinterventionalSponsorWashington University School of MedicineRan2022 to 2023Enrolled18ConditionsEpilepsyArmsEmpagliflozin 25 mg, Placebo
NCT07174687 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

Efficacy of Dapagliflozin in the Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration

TypeinterventionalSponsorWashington University School of MedicineRan2025 to 2028Enrolled70ConditionsRetinal Degeneration, Retinal Diseases, Eye Diseases, Geographic AtrophyArmsDapagliflozin, Matching Placebo
3 · Its place in the literature

Who cites it

337 citing papers in PubMed, 4 syntheses or guidelines pooled it, 495 citations in OpenAlex.

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  18. Impact of SGLT2 inhibitors in cardiac amyloidosis: A systematic review and meta-analysis.American heart journal plus : cardiology research and practice · 2026
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277 more citing papers are in PubMed but not listed here.

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

22 authors at 2 institutions in 1 country.

So Ra Kim *Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0002-5778-370X
Sang-Guk Lee *Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0003-3862-3660
Soo Hyun KimDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Jin Hee KimDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0002-1999-3095
Eunhye ChoiDepartment of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Wonhee ChoExercise Medicine Center for Diabetes and Cancer Patients, ICONS, Yonsei University, Seoul, 03722, Republic of Korea.
John Hoon RimBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Inhwa HwangBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Chan Joo LeeCardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Minyoung LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Chang-Myung OhDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Justin Y JeonExercise Medicine Center for Diabetes and Cancer Patients, ICONS, Yonsei University, Seoul, 03722, Republic of Korea.
Heon Yung GeeBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0002-8741-6177
Jeong-Ho KimDepartment of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0003-2479-0548
Byung-Wan LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0002-9899-4992
Eun Seok KangDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Bong-Soo ChaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Myung-Shik LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.ORCID http://orcid.org/0000-0003-3292-1720
Je-Wook YuBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Jin Won ChoDepartment of Systems Biology, Glycosylation Network Research Center, Yonsei University, Seoul, 03722, Republic of Korea.
Jung-Sun KimCardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. KJS1218@yuhs.ac.ORCID http://orcid.org/0000-0003-2263-3274
Yong-Ho LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. yholee@yuhs.ac.ORCID http://orcid.org/0000-0002-6219-4942
Yonsei University · KRGwangju Institute of Science and Technology · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.

Indexed as

AgedAnimalsCardiovascular DiseasesDiabetes Mellitus, Type 2GlucoseHumansInflammasomesInsulinInterleukin-1betaKetonesMacrophagesMiddle AgedNLR Family, Pyrin Domain-Containing 3 ProteinSodium-Glucose Transporter 2 InhibitorsSulfonylurea CompoundsTumor Necrosis Factor-alphaGlucoseInflammasomesInsulinInterleukin-1betaKetonesNLR Family, Pyrin Domain-Containing 3 ProteinSodium-Glucose Transporter 2 InhibitorsSulfonylurea CompoundsTumor Necrosis Factor-alpha

Identifiers

PMID32358544
PMCPMC7195385
OpenAlexW3023354007

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.