Skip to main content

Advertisement

Springer Nature Link
Log in

Use of SGLT2 inhibitors and occurrence of noninfectious respiratory disorders: a meta-analysis of large randomized trials of SGLT2 inhibitors

  • Meta- Analysis
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

The impact of use of sodium-glucose transporter 2 (SGLT2) inhibitors on occurrence of various kinds of respiratory disorders has not been established. We aimed at evaluating the relationship between use of SGLT2 inhibitors and occurrence of 9 kinds of noninfectious respiratory disorders.

Methods

Large randomized controlled trials (RCTs) of SGLT2 inhibitors were included in this study. We conducted fixed-effects meta-analysis to synthesize risk ratios (RRs) and 95% confidence intervals (CIs). We did subgroup analysis respectively stratified by type of underlying diseases and type of SGLT2 inhibitors.

Results

Nine Large RCTs were included for analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the occurrence of overall respiratory disorders (RR 0.75, 95% CI 0.62–0.91), acute pulmonary oedema (RR 0.51, 95% CI 0.29–0.88), asthma (RR 0.57, 95% CI 0.33–0.995), and sleep apnoea syndrome (RR 0.35, 95% CI 0.12–0.99). SGLT2 inhibitors showed the reduced trends in the risks of chronic obstructive pulmonary disease (COPD) (RR 0.79, 95% CI 0.61–1.02; P = 0.073) and pulmonary hypertension (RR 0.43, 95% CI 0.16–1.17; P = 0.098). SGLT2 inhibitors had no significant effects on three other respiratory disorders. These effects exhibited by SGLT2 inhibitors were consistent across different underlying diseases (Psubgroup ≥0.209) and different SGLT2 inhibitors (Psubgroup ≥0.192).

Conclusions

SGLT2 inhibitors can significantly reduce the occurrence of acute pulmonary oedema, asthma, and sleep apnoea syndrome; and produce the reduced trends in the risks of COPD and pulmonary hypertension. These findings will prompt further investigation on SGLT2 inhibitors for primary and secondary prevention of various respiratory disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

SGLT2 inhibitors:

sodium-glucose transporter 2 inhibitors

T2D:

type 2 diabetes

HF:

heart failure

CKD:

chronic kidney disease

RR:

risk ratio

CI:

confidence interval

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCTs:

randomized controlled trials

ARDS:

acute respiratory distress syndrome

COPD:

chronic obstructive pulmonary disease

ILD:

interstitial lung disease

PH:

pulmonary hypertension

RF:

respiratory failure

Psubgroup:

p for subgroup differences.

References

  1. C.P. Cannon, R. Pratley, S. Dagogo-Jack et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med 383(15), 1425–1435 (2020)

    Article  CAS  Google Scholar 

  2. V. Perkovic, M.J. Jardine, B. Neal et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380(24), 2295–2306 (2019)

    Article  CAS  Google Scholar 

  3. S.D. Wiviott, I. Raz, M.P. Bonaca et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 380(4), 347–357 (2019)

    Article  CAS  Google Scholar 

  4. B. Neal, V. Perkovic, K.W. Mahaffey et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377(7), 644–657 (2017)

    Article  CAS  Google Scholar 

  5. B. Zinman, C. Wanner, J.M. Lachin et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22), 2117–2128 (2015)

    Article  CAS  Google Scholar 

  6. M. Packer, S.D. Anker, J. Butler et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 383(15), 1413–1424 (2020)

    Article  CAS  Google Scholar 

  7. J. McMurray, S.D. Solomon, S.E. Inzucchi et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 381(21), 1995–2008 (2019)

    Article  CAS  Google Scholar 

  8. H. Heerspink, B.V. Stefánsson, R. Correa-Rotter et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 383(15), 1436–1446 (2020)

    Article  CAS  Google Scholar 

  9. Y. Tang, Q. Sun, X.Y. Bai, Y.F. Zhou, Q.L. Zhou, M. Zhang, Effect of dapagliflozin on obstructive sleep apnea in patients with type 2 diabetes: a preliminary study. NUTR DIABETES 9(1), 32 (2019)

    Article  Google Scholar 

  10. S. Furukawa, T. Miyake, H. Senba et al. The effectiveness of dapagliflozin for sleep-disordered breathing among japanese patients with obesity and type 2 diabetes mellitus. ENDOCR J 65(9), 953–961 (2018)

    Article  CAS  Google Scholar 

  11. K. Sawada, S. Karashima, M. Kometani et al. Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in patients with type 2 diabetes. ENDOCR J 65(4), 461–467 (2018)

    Article  CAS  Google Scholar 

  12. D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman, Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. PLOS Med 6(7), e1000097 (2009)

    Article  Google Scholar 

  13. J.P. Higgins, D.G. Altman, P.C. Gotzsche et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343, d5928 (2011)

    Article  Google Scholar 

  14. J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G.A. Measuring, inconsistency in meta-analyses. BMJ 327(7414), 557–560 (2003)

    Article  Google Scholar 

  15. J.P. Higgins, S.G. Thompson, Quantifying heterogeneity in a meta-analysis. Stat Med 21(11), 1539–1558 (2002)

    Article  Google Scholar 

  16. S. Brikman, G. Dori, Sodium glucose cotransporter2 inhibitor-possible treatment for patients with diabetes, pulmonary disease and co(2) retention. Med Hypotheses 139, 109631 (2020)

    Article  CAS  Google Scholar 

  17. B. Chowdhury, A.Z. Luu, V.Z. Luu et al. The sglt2 inhibitor empagliflozin reduces mortality and prevents progression in experimental pulmonary hypertension. Biochem Biophys Res Commun 524(1), 50–56 (2020)

    Article  CAS  Google Scholar 

  18. H.J. Park, H. Han, E.Y. Oh et al. Empagliflozin and dulaglutide are effective against obesity-induced airway hyperresponsiveness and fibrosis in a murine model. Sci Rep 9(1), 15601 (2019)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China

    Mei Qiu

  2. Department of Endocrinology, First Affiliated Hospital of Yangtze University, Jingzhou, China

    Liang-Liang Ding

  3. Class 3, Clinical Medicine, Grade 2019, The Second Clinical Medical College, Southern Medical University, Guangzhou, China

    Ze-Lin Zhan

  4. Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

    Shu-Yan Liu

Authors
  1. Mei Qiu
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Liang-Liang Ding
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Ze-Lin Zhan
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Shu-Yan Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Mei Qiu.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qiu, M., Ding, LL., Zhan, ZL. et al. Use of SGLT2 inhibitors and occurrence of noninfectious respiratory disorders: a meta-analysis of large randomized trials of SGLT2 inhibitors. Endocrine 73, 31–36 (2021). https://doi.org/10.1007/s12020-021-02644-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02644-x

Keywords