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Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI
  1. Sazan Rasul1,
  2. Barbara Katharina Geist1,
  3. Helmut Brath2,
  4. Pascal Baltzer3,
  5. Lalith Kumar Shiyam Sundar4,
  6. Verena Pichler1,
  7. Markus Mitterhauser5,
  8. Alexandra Kautzky-Willer6,
  9. Marcus Hacker1
  1. 1Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
  2. 2Diabetes & Metabolic Outpatient Clinic, Health Centre Vienna South, Vienna, Austria
  3. 3Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Vienna, Austria
  4. 4Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  5. 5Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria
  6. 6Department of Internal Medicine III, Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Dr Barbara Katharina Geist; barbara.geist{at}meduniwien.ac.at

Abstract

Introduction Inhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.

Methods PET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls.

Results MTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; p<0.001). The higher the GRP value in kidneys of T2DMSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation.

Conclusion MTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy.

Trial registration number NCT03557138.

  • sodium glucose cotransporter
  • PET (positive emission tomography)
  • type 2 diabetes
  • renal function
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Footnotes

  • Contributors SR wrote the manuscript, researched the data, contributed to discussion. BKG researched and analyzed the data, contributed to discussion. HB researched the data, contributed to discussion. PB and LKSS researched the data. VP and MM reviewed the manuscript. AK-W designed the study, contributed to discussion, reviewed the manuscript. MH wrote the manuscript, designed the study, contributed to discussion, reviewed/edited the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The local institutional ethics committee of Medical University of Vienna has approved the study (EK: 1128/2016).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request after passing a legal transaction form by the university.

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