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The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF)

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Abstract

Purpose

A recent large cardiovascular outcome trial in patients with type 2 diabetes (T2DM) demonstrated excess heart failure hospitalization with saxagliptin. We sought to evaluate the impact of saxagliptin on cardiac structure and function using cardiac magnetic resonance imaging (CMR) in patients with T2DM without pre-existing heart failure.

Methods

In this prospective study, patients with T2DM without heart failure were prescribed saxagliptin as part of routine guideline-directed management. Clinical assessment, CMR imaging and biomarkers were assessed in a blinded fashion and compared following 6 months of continued treatment. The primary outcome was the change in left ventricular (LV) ejection fraction (LVEF) after 6 months of therapy. Key secondary outcomes included changes in LV and right ventricular (RV) end-diastolic volume, ventricular mass, LV global strain and cardiac biomarkers [N terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP)] over 6 months.

Results

The cohort (n = 16) had a mean age of 59.9 years with 69% being male. The mean hemoglobin A1c (HbA1c) was 8.3%. Mean baseline LVEF was 57% ± 3.4, with no significant change over 6 months (− 0.2%, 95% CI − 2.5, 2.1, p = 0.86). Detailed CMR analyses that included LV/RV volumes, LV mass, and feature tracking-derived strain showed no significant change (all p > 0.50). NT-proBNP and hsCRP levels did not significantly change (p > 0.20).

Conclusions

In this cohort of stable ambulatory patients with T2DM without heart failure, saxagliptin treatment was not associated with adverse ventricular remodeling over 6 months as assessed using CMR and biomarkers.

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Funding

The proposal was funded by an unrestricted educational Grant from Astra Zeneca, who manufacture saxagliptin.

Author information

Author notes

  1. Paul Sandhu and Jann P. Ong have contributed equally to the work.

Authors and Affiliations

  1. Division of Cardiology, Queen’s University, Kingston, ON, Canada

    Paul Sandhu

  2. Division of Cardiology, University of Toronto, Toronto, ON, Canada

    Jann P. Ong, Vinay Garg, Mustafa Altaha & Olubenga Bello

  3. Department of Medicine, Humber River Hospital, Toronto, ON, Canada

    Sewa R. Singal

  4. Department of Medicine, Queen’s University, Kingston, ON, Canada

    Sewa R. Singal

  5. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON, Canada

    Subodh Verma

  6. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Subodh Verma

  7. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Subodh Verma

  8. Department of Physiology, University of Toronto, Toronto, ON, Canada

    Subodh Verma & Kim A. Connelly

  9. Division of Cardiology, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, 193 Yonge St, Toronto, ON, M5B1M8, Canada

    Andrew T. Yan & Kim A. Connelly

  10. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Andrew T. Yan & Kim A. Connelly

Authors
  1. Paul Sandhu
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  2. Jann P. Ong
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  9. Kim A. Connelly
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Corresponding author

Correspondence to Kim A. Connelly.

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Conflict of interest

Dr Connelly is listed as an inventor on a patent application by Boehringer Ingelheim on the use of dipeptidyl peptidase-4 inhibitors in heart failure; and reports receiving research grants to his institution from AstraZeneca, Servier, and Boehringer Ingelheim; support for travel to scientific meetings from Boehringer Ingelheim and honoraria for speaking engagements and ad hoc participation in advisory boards from Servier, Merck, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Ferring, Novo Nordisk, Novartis, and Janssen.

Ethics 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.

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Data can be made available upon request.

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Managed by Antonio Secchi.

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Sandhu, P., Ong, J.P., Garg, V. et al. The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF). Acta Diabetol 58, 633–641 (2021). https://doi.org/10.1007/s00592-020-01661-y

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  • DOI: https://doi.org/10.1007/s00592-020-01661-y

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