Skip to content
2000
Volume 23, Issue 3
  • ISSN: 1570-1611
  • E-ISSN: 1875-6212

Abstract

Introduction

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk.

Aims

This systematic review and meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on EAT.

Methods

We performed a literature search for studies assessing the changes in epicardial adipose tissue volume/thickness before and after treatment with an SGLT2 inhibitor. We excluded reviews, editorials, case reports/case series, experimental studies, and studies that did not use SGLT2 inhibitors as the intervention. The main outcome of interest was the change in EAT volume/thickness at follow-up.

Results

The literature search yielded 72 results. After the application of the exclusion criteria, a total of 11 studies were selected for data extraction and inclusion in the meta-analysis. A mean of 6.57ml decreased EAT volume, and EAT thickness was reduced by a mean of 1.55mm. We detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness compared to the control group (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial between-study heterogeneity (I2: 94%, p<0.001). Results remained robust even after the exclusion of any single study. Subgroup analysis revealed a significantly greater effect size in randomized studies. Funnel plot inspection and Egger’s regression test did not indicate the presence of publication bias.

Conclusion

This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure (HF) outcomes.

Loading

Article metrics loading...

/content/journals/cvp/10.2174/0115701611330060241204062248
2025-01-15
2025-05-24
Loading full text...

Full text loading...

References

  1. SaeediP. PetersohnI. SalpeaP. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Res Clin Pract.201915710784310.1016/j.diabres.2019.107843 31518657
    [Google Scholar]
  2. LingW. HuangY. HuangY.M. FanR.R. SuiY. ZhaoH.L. Global trend of diabetes mortality attributed to vascular complications, 2000–2016.Cardiovasc. Diabetol.202019118210.1186/s12933‑020‑01159‑5 33081808
    [Google Scholar]
  3. EinarsonT.R. AcsA. LudwigC. PantonU.H. Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007–2017.Cardiovasc. Diabetol.20181718310.1186/s12933‑018‑0728‑6 29884191
    [Google Scholar]
  4. ZhaoN. YuX. ZhuX. Diabetes mellitus to accelerated atherosclerosis: Shared cellular and molecular mechanisms in glucose and lipid metabolism.J. Cardiovasc. Transl. Res.202417113315210.1007/s12265‑023‑10470‑x 38091232
    [Google Scholar]
  5. JakubiakG.K. PawlasN. CieślarG. StanekA. Pathogenesis and clinical significance of in-stent restenosis in patients with diabetes.Int. J. Environ. Res. Public Health202118221197010.3390/ijerph182211970 34831726
    [Google Scholar]
  6. TheofilisP. OikonomouE. TsioufisK. TousoulisD. Diabetes mellitus and heart failure: Epidemiology, pathophysiologic mechanisms, and the role of SGLT2 inhibitors.Life202313249710.3390/life13020497 36836854
    [Google Scholar]
  7. VaduganathanM. DochertyK.F. ClaggettB.L. SGLT2 inhibitors in patients with heart failure: A comprehensive meta-analysis of five randomised controlled trials.Lancet20224001035475776710.1016/S0140‑6736(22)01429‑5 36041474
    [Google Scholar]
  8. TheofilisP. KalaitzidisR.G. SGLT2 inhibitors and kidney diseases: A clinical perspective.Curr. Med. Chem.202330232595260310.2174/0929867330666221227091943 36578262
    [Google Scholar]
  9. DutkaM. BobińskiR. FrancuzT. SGLT2 inhibitors in cancer treatment—mechanisms of action and emerging new perspectives.Cancers20221423581110.3390/cancers14235811 36497303
    [Google Scholar]
  10. BenedettiR. BenincasaG. GlassK. Effects of novel SGLT2 inhibitors on cancer incidence in hyperglycemic patients: A meta-analysis of randomized clinical trials.Pharmacol. Res.202217510603910.1016/j.phrs.2021.106039 34929299
    [Google Scholar]
  11. TheofilisP. SagrisM. OikonomouE. Pleiotropic effects of SGLT2 inhibitors and heart failure outcomes.Diabetes Res. Clin. Pract.202218810992710.1016/j.diabres.2022.109927 35577035
    [Google Scholar]
  12. TheofilisP. SagrisM. OikonomouE. The impact of SGLT2 inhibitors on inflammation: A systematic review and meta-analysis of studies in rodents.Int. Immunopharmacol.202211110908010.1016/j.intimp.2022.109080 35908505
    [Google Scholar]
  13. IacobellisG. Epicardial adipose tissue in contemporary cardiology.Nat. Rev. Cardiol.202219959360610.1038/s41569‑022‑00679‑9 35296869
    [Google Scholar]
  14. van WoerdenG. van VeldhuisenD.J. WestenbrinkB.D. de BoerR.A. RienstraM. GorterT.M. Connecting epicardial adipose tissue and heart failure with preserved ejection fraction: Mechanisms, management and modern perspectives.Eur. J. Heart Fail.202224122238225010.1002/ejhf.2741 36394512
    [Google Scholar]
  15. PageM.J. McKenzieJ.E. BossuytP.M. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.BMJ202137271n7110.1136/bmj.n71 33782057
    [Google Scholar]
  16. DownsS.H. BlackN. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.J. Epidemiol. Community Health199852637738410.1136/jech.52.6.377 9764259
    [Google Scholar]
  17. HigginsJ.P.T. ThompsonS.G. DeeksJ.J. AltmanD.G. Measuring inconsistency in meta-analyses.BMJ2003327741455756010.1136/bmj.327.7414.557 12958120
    [Google Scholar]
  18. Introduction to Meta‐Analysis20092132
    [Google Scholar]
  19. ViechtbauerW. CheungM.W.L. Outlier and influence diagnostics for meta-analysis.Res. Synth. Methods20101211212510.1002/jrsm.11 26061377
    [Google Scholar]
  20. OlkinI. DahabrehI.J. TrikalinosT.A. GOSH – a graphical display of study heterogeneity.Res. Synth. Methods20123321422310.1002/jrsm.1053 26062164
    [Google Scholar]
  21. LinL. ChuH. Quantifying publication bias in meta-analysis.Biometrics201874378579410.1111/biom.12817 29141096
    [Google Scholar]
  22. ZwetslootP.P. Van Der NaaldM. SenaE.S. HowellsD.W. Standardized mean differences cause funnel plot distortion in publication bias assessments.eLife20176
    [Google Scholar]
  23. GaboritB. AncelP. AbdullahA.E. Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: The EMPACEF study.Cardiovasc. Diabetol.20212015710.1186/s12933‑021‑01237‑2 33648515
    [Google Scholar]
  24. SatoT. AizawaY. YuasaS. The effect of dapagliflozin treatment on epicardial adipose tissue volume.Cardiovasc. Diabetol.2018171610.1186/s12933‑017‑0658‑8 29301516
    [Google Scholar]
  25. Macías-CervantesH.E. Martínez-RamírezD.B. Hinojosa-GutiérrezL.R. Córdova-SilvaD.A. Rios-MuñozJ.A. Effect of dapagliflozin on epicardial fat volume in patients with acute coronary syndrome assessed by computed tomography.Curr. Probl. Cardiol.202449210221310.1016/j.cpcardiol.2023.102213 38000564
    [Google Scholar]
  26. Requena-IbáñezJ.A. Santos-GallegoC.G. Rodriguez-CorderoA. Mechanistic insights of empagliflozin in nondiabetic patients with HFrEF.JACC Heart Fail.20219857858910.1016/j.jchf.2021.04.014 34325888
    [Google Scholar]
  27. CintiF. LeccisottiL. SoriceG.P. Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.Cardiovasc. Diabetol.202322134910.1186/s12933‑023‑02091‑0 38115004
    [Google Scholar]
  28. IacobellisG. Gra-MenendezS. Effects of dapagliflozin on epicardial fat thickness in patients with type 2 diabetes and obesity.Obesity20202861068107410.1002/oby.22798 32352644
    [Google Scholar]
  29. SongX. WeiY. RuiY. FanL. Echocardiographic evaluation of the effect of dapagliflozin on epicardial adipose tissue and left ventricular systolic function in type 2 diabetes mellitus.J. Diabetes Complications202337710850910.1016/j.jdiacomp.2023.108509 37235925
    [Google Scholar]
  30. BrahaA. AlbaiA. TimarB. Predictors of epicardial fat volume decrease after dapagliflozin treatment in patients with type 2 diabetes.Medicina20215812110.3390/medicina58010021 35056329
    [Google Scholar]
  31. YagiS. HirataY. IseT. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus.Diabetol. Metab. Syndr.2017917810.1186/s13098‑017‑0275‑4 29034006
    [Google Scholar]
  32. FukudaT. BouchiR. TerashimaM. Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: A pilot study.Diabetes Ther.20178485186110.1007/s13300‑017‑0279‑y 28616806
    [Google Scholar]
  33. BouchiR. TerashimaM. SasaharaY. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: A pilot study.Cardiovasc. Diabetol.20171613210.1186/s12933‑017‑0516‑8 28253918
    [Google Scholar]
  34. DoeschC. HaghiD. FlüchterS. Epicardial adipose tissue in patients with heart failure.J. Cardiovasc. Magn. Reson.20101214010.1186/1532‑429X‑12‑40 20624277
    [Google Scholar]
  35. Fontes-CarvalhoR. Fontes-OliveiraM. SampaioF. Influence of epicardial and visceral fat on left ventricular diastolic and systolic functions in patients after myocardial infarction.Am. J. Cardiol.2014114111663166910.1016/j.amjcard.2014.08.037 25306552
    [Google Scholar]
  36. van WoerdenG. GorterT.M. WestenbrinkB.D. WillemsT.P. van VeldhuisenD.J. RienstraM. Epicardial fat in heart failure patients with mid-range and preserved ejection fraction.Eur. J. Heart Fail.201820111559156610.1002/ejhf.1283 30070041
    [Google Scholar]
  37. TentolourisA. VlachakisP. TzeraviniE. EleftheriadouI. TentolourisN. SGLT2 inhibitors: A review of their antidiabetic and cardioprotective effects.Int. J. Environ. Res. Public Health20191616296510.3390/ijerph16162965 31426529
    [Google Scholar]
  38. AgraR.M. Teijeira-FernándezE. Pascual-FigalD. Adiponectin and p53 mRNA in epicardial and subcutaneous fat from heart failure patients.Eur. J. Clin. Invest.2014441293710.1111/eci.12186 24117366
    [Google Scholar]
  39. ZhaoL. GuoZ. WangP. Proteomics of epicardial adipose tissue in patients with heart failure.J. Cell. Mol. Med.202024151152010.1111/jcmm.14758 31670476
    [Google Scholar]
  40. DoeschC. StreitnerF. BellmS. Epicardial adipose tissue assessed by cardiac magnetic resonance imaging in patients with heart failure due to dilated cardiomyopathy.Obesity2013213E253E26110.1002/oby.20149 23592680
    [Google Scholar]
  41. WuC.K. TsaiH.Y. SuM.Y.M. Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients.J. Clin. Lipidol.20171161421143110.1016/j.jacl.2017.08.018 29050981
    [Google Scholar]
  42. LymperopoulosA. RengoG. GaoE. EbertS.N. DornG.W.II KochW.J. Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction.J. Biol. Chem.201028521163781638610.1074/jbc.M109.077859 20351116
    [Google Scholar]
  43. LymperopoulosA. RengoG. FunakoshiH. EckhartA.D. KochW.J. Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure.Nat. Med.200713331532310.1038/nm1553 17322894
    [Google Scholar]
  44. WhiteI.A. Cardiac sympathetic denervation in the failing heart.Circ. Res.201611881189119110.1161/CIRCRESAHA.116.308621 27081107
    [Google Scholar]
  45. LuC. JiaH. WangZ. Association between epicardial adipose tissue and adverse outcomes in coronary heart disease patients with percutaneous coronary intervention.Biosci. Rep.2019395BSR2018227810.1042/BSR20182278 30979830
    [Google Scholar]
  46. YaribeygiH. MalekiM. ButlerA.E. JamialahmadiT. SahebkarA. Sodium-glucose co-transporter-2 inhibitors and epicardial adiposity.Eur. J. Pharm. Sci.202318010632210.1016/j.ejps.2022.106322 36336279
    [Google Scholar]
  47. MyasoedovaV.A. ParisiV. MoschettaD. Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: A systematic review and meta-analysis.Cardiovasc. Diabetol.20232212310.1186/s12933‑023‑01738‑2 36721184
    [Google Scholar]
  48. LazarosG. AntonopoulosA.S. OikonomouE.K. Prognostic implications of epicardial fat volume quantification in acute pericarditis.Eur. J. Clin. Invest.201747212913610.1111/eci.12711 27931089
    [Google Scholar]
  49. PoggiA.L. GaboritB. SchindlerT.H. LiberaleL. MontecuccoF. CarboneF. Epicardial fat and atrial fibrillation: The perils of atrial failure.Europace20222481201121210.1093/europace/euac015 35274140
    [Google Scholar]
  50. OrciL.A. JornayvazF.R. TosoC. GarianiK. Systematic review and meta-analysis of the usefulness of epicardial fat thickness as a non-invasive marker of the presence and severity of nonalcoholic fatty liver disease.Biomedicines2022109220410.3390/biomedicines10092204 36140303
    [Google Scholar]
/content/journals/cvp/10.2174/0115701611330060241204062248
Loading
/content/journals/cvp/10.2174/0115701611330060241204062248
Loading

Data & Media loading...

Supplements

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test