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Relationship between saxagliptin use and left ventricular diastolic function assessed by cardiac MRI

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Abstract

Aims

Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6 months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM.

Methods

In this prospective study, 16 T2DM patients without HF were prescribed saxagliptin as part of routine guideline-directed management. CMR performed at baseline and 6 months after initiation of saxagliptin treatment were evaluated in a blinded fashion. We assessed LV diastolic function by measuring LV peak filling rate with correction for end-diastolic volume (PFR/LVEDV), time to peak filling rate with correction for cardiac cycle (TPF/RR), and early diastolic strain rate parameters [global longitudinal diastolic strain rate (GLSR-E), global circumferential diastolic strain rate (GCSR-E)] by feature tracking (FT-CMR).

Results

Among the 16 patients (mean age of 59.9, 69% males, mean hemoglobin A1c 8.3%, mean left ventricular ejection fraction 57%), mean PFR was 314 ± 108 ml/s at baseline and did not change over 6 months (− 2.7, 95% CI − 35.6, 30.2, p = 0.86). There were also no significant changes in other diastolic parameters including PFR/EDV, TPF, TPF/RR, and GLSR-E and GCSR-E (all p > 0.50).

Conclusion

In T2DM patients without HF receiving saxagliptin over 6 months, there were no significant subclinical changes in LV diastolic function as assessed by CMR.

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Data availability

Data can be made available upon request.

References

  1. Kenny HC, Abel ED (2019) Heart failure in type 2 diabetes mellitus. Circ Res 124:121–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lipscombe L, Butalia S, Dasgupta K et al (2020) Pharmacologic glycemic management of type 2 diabetes in adults: 2020 update. Can J Diabetes 44:575–591

    Article  PubMed  Google Scholar 

  3. Lo S, Leiter LA, Langer A et al (2021) Cardiovascular risk factor management in patients with diabetes: does management differ with disease duration? J Diabetes Complicat 35:107997

    Article  CAS  Google Scholar 

  4. Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326

    Article  CAS  PubMed  Google Scholar 

  5. Scirica BM, Braunwald E, Raz I et al (2014) Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 130:1579–1588

    Article  CAS  PubMed  Google Scholar 

  6. Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ (2000) Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2:271–278

    Article  CAS  PubMed  Google Scholar 

  7. Pennell DJ (2010) Cardiovascular magnetic resonance. Circulation 121:692–705

    Article  PubMed  Google Scholar 

  8. Westenberg JJ (2011) CMR for assessment of diastolic function. Curr Cardiovasc Imaging Rep 4:149–158

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zile MR, Brutsaert DL (2002) New concepts in diastolic dysfunction and diastolic heart failure: part I: diagnosis, prognosis, and measurements of diastolic function. Circulation 105:1387–1393

    Article  PubMed  Google Scholar 

  10. Aljaroudi W, Alraies MC, Halley C et al (2012) Impact of progression of diastolic dysfunction on mortality in patients with normal ejection fraction. Circulation 125:782–788

    Article  PubMed  Google Scholar 

  11. Sandhu P, Ong JP, Garg V et al (2021) The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF). Acta Diabetol 58:633–641

    Article  CAS  PubMed  Google Scholar 

  12. Paelinck BP, Lamb HJ, Bax JJ, Van der Wall EE, de Roos A (2002) Assessment of diastolic function by cardiovascular magnetic resonance. Am Heart J 144:198–205

    Article  PubMed  Google Scholar 

  13. Gong IY, Ong G, Brezden-Masley C et al (2019) Early diastolic strain rate measurements by cardiac MRI in breast cancer patients treated with trastuzumab: a longitudinal study. Int J Cardiovasc Imaging 35:653–662

    Article  PubMed  Google Scholar 

  14. Scatteia A, Baritussio A, Bucciarelli-Ducci C (2017) Strain imaging using cardiac magnetic resonance. Heart Fail Rev 22:465–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ng MY, Tong X, He J et al (2020) Feature tracking for assessment of diastolic function by cardiovascular magnetic resonance imaging. Clin Radiol 75:321 e1-321 e1

    Article  PubMed  Google Scholar 

  16. McMurray JJV, Ponikowski P, Bolli GB et al (2018) Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. JACC Heart Fail 6:8–17

    Article  PubMed  Google Scholar 

  17. Nogueira KC, Furtado M, Fukui RT et al (2014) Left ventricular diastolic function in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor: a pilot study. Diabetol Metab Syndr 6:103

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yamada H, Tanaka A, Kusunose K et al (2017) Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study. Cardiovasc Diabetol 16:63

    Article  PubMed  PubMed Central  Google Scholar 

  19. Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373:232–242

    Article  CAS  PubMed  Google Scholar 

  20. Toh S, Hampp C, Reichman ME et al (2016) Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Intern Med 164:705–714

    Article  PubMed  PubMed Central  Google Scholar 

  21. Borlaug BA, Redfield MM (2011) Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation 123:2006–2013

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wong TC, Piehler KM, Kang IA et al (2014) Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission. Eur Heart J 35:657–664

    Article  CAS  PubMed  Google Scholar 

  23. Shang Y, Zhang X, Leng W et al (2017) Assessment of diabetic cardiomyopathy by cardiovascular magnetic resonance T1 mapping: correlation with left-ventricular diastolic dysfunction and diabetic duration. J Diabetes Res 2017:9584278

    Article  PubMed  PubMed Central  Google Scholar 

  24. Caudron J, Fares J, Bauer F, Dacher JN (2011) Evaluation of left ventricular diastolic function with cardiac MR imaging. Radiographics 31:239–259

    Article  PubMed  Google Scholar 

  25. Kankanala SR, Syed R, Gong Q, Ren B, Rao X, Zhong J (2016) Cardiovascular safety of dipeptidyl peptidase-4 inhibitors: recent evidence on heart failure. Am J Transl Res 8:2450–2458

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Tadic M, Sala C, Saeed S et al (2022) New antidiabetic therapy and HFpEF: light at the end of tunnel? Heart Fail Rev 27:1137–1146

    Article  CAS  PubMed  Google Scholar 

  27. Connelly KA, Zhang Y, Advani A et al (2013) DPP-4 inhibition attenuates cardiac dysfunction and adverse remodeling following myocardial infarction in rats with experimental diabetes. Cardiovasc Ther 31:259–267

    Article  CAS  PubMed  Google Scholar 

  28. Hiemstra JA, Lee DI, Chakir K et al (2016) Saxagliptin and tadalafil differentially alter cyclic guanosine monophosphate (cGMP) signaling and left ventricular function in aortic-banded mini-swine. J Am Heart Assoc 5:e003277

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are indebted to all the patients and study staff who contributed to this study.

Funding

The proposal was funded by an unrestricted educational grant from Astra Zeneca that manufactures saxagliptin.

Author information

Authors and Affiliations

  1. Department of Medical Imaging, St. Michael’s Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada

    Kathy C. K. Wong, Huda S. Ismail, Djeven P. Deva, Andrew T. Yan & Laura Jimenez-Juan

  2. Department of Medical Imaging, University of Toronto, Toronto, Canada

    Kathy C. K. Wong, Huda S. Ismail, Djeven P. Deva, Andrew T. Yan & Laura Jimenez-Juan

  3. Department of Diagnostic Radiology, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Kathy C. K. Wong & Ming-Yen Ng

  4. Division of Cardiology, St. Michael’s Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada

    Kim A. Connelly & Andrew T. Yan

  5. Department of Medicine, University of Toronto, Toronto, Canada

    Kim A. Connelly & Andrew T. Yan

  6. Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute of Unity Health Toronto, Toronto, Canada

    Kim A. Connelly, Subodh Verma, Djeven P. Deva & Laura Jimenez-Juan

  7. Division of Cardiac Surgery, St. Michael’s Hospital, Toronto, Canada

    Subodh Verma

  8. Department of Surgery and Pharmacology and Toxicology, University of Toronto, Toronto, Canada

    Subodh Verma

  9. Division of Cardiac Imaging, HKU-Shenzhen Hospital, Shenzhen, China

    Ming-Yen Ng

Authors
  1. Kathy C. K. Wong
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  2. Huda S. Ismail
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  3. Kim A. Connelly
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  4. Subodh Verma
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  5. Ming-Yen Ng
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  6. Djeven P. Deva
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  7. Andrew T. Yan
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  8. Laura Jimenez-Juan
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Corresponding authors

Correspondence to Andrew T. Yan or Laura Jimenez-Juan.

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Conflicts of interest

Dr KCK Wong, no conflicts. Dr HS Ismail, no conflicts. Dr KA Connelly holds the Keenan Chair in Research Leadership at Unity Health Toronto, University of Toronto and reports receiving research grants to his institution from AstraZeneca and Boehringer Ingelheim, support for travel to scientific meeting from Boehringer Ingelheim and honoraria for speaking engagements and ad hoc participation in advisory boards from AstraZeneca, Boehringer Ingelheim and Janssen. Dr S Verma reports receiving research grant support and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, and S&L Solutions. Dr Verma is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization Dr MY Ng reports receiving research grant support and/or speaking/consulting honoraria from Circle, Bayer, TeraRecon, GE and Boehringer Ingelheim. Dr DP Deva, no conflicts. Dr AT Yan reports receiving research grant support from AstraZeneca. Dr Laura Jimenez-Juan, no conflicts.

Ethical approval

The study was approved by St. Michael’s Hospital Research Ethics Board.

Consent to participate

All participants were consented to participate. Study team ensured that participants were made aware that participation or lack thereof will have no impact on clinical care provided.

Consent for publication

Waived.

Additional information

Managed by Antonio Secchi .

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Wong, K.C.K., Ismail, H.S., Connelly, K.A. et al. Relationship between saxagliptin use and left ventricular diastolic function assessed by cardiac MRI. Acta Diabetol 61, 91–97 (2024). https://doi.org/10.1007/s00592-023-02177-x

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  • DOI: https://doi.org/10.1007/s00592-023-02177-x

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