Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report
Abstract Objective Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-09-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-022-01607-4 |
| _version_ | 1798004344817188864 |
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| author | Lucia Leccisotti Francesca Cinti Gian Pio Sorice Domenico D’Amario Margherita Lorusso Maria Angela Guzzardi Teresa Mezza Shawn Gugliandolo Camilla Cocchi Umberto Capece Luca Indovina Pietro Manuel Ferraro Patricia Iozzo Filippo Crea Alessandro Giordano Andrea Giaccari |
| author_facet | Lucia Leccisotti Francesca Cinti Gian Pio Sorice Domenico D’Amario Margherita Lorusso Maria Angela Guzzardi Teresa Mezza Shawn Gugliandolo Camilla Cocchi Umberto Capece Luca Indovina Pietro Manuel Ferraro Patricia Iozzo Filippo Crea Alessandro Giordano Andrea Giaccari |
| author_sort | Lucia Leccisotti |
| collection | DOAJ |
| description | Abstract Objective Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF. Methods This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752). Results 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). Conclusions SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752 |
| first_indexed | 2024-04-11T12:22:17Z |
| format | Article |
| id | doaj.art-187853d7eb7e446eb739e207319cad8b |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-11T12:22:17Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-187853d7eb7e446eb739e207319cad8b2022-12-22T04:24:03ZengBMCCardiovascular Diabetology1475-28402022-09-0121111010.1186/s12933-022-01607-4Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary reportLucia Leccisotti0Francesca Cinti1Gian Pio Sorice2Domenico D’Amario3Margherita Lorusso4Maria Angela Guzzardi5Teresa Mezza6Shawn Gugliandolo7Camilla Cocchi8Umberto Capece9Luca Indovina10Pietro Manuel Ferraro11Patricia Iozzo12Filippo Crea13Alessandro Giordano14Andrea Giaccari15UOC Di Medicina Nucleare, Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreCentro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreCentro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreUOC Di Cardiologia, Dipartimento Di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, and Università Cattolica del Sacro CuoreUOC Di Medicina Nucleare, Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreIstituto Di Fisiologia Clinica, Consiglio Nazionale Delle Ricerche (CNR)Centro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreCentro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreCentro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreCentro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreUOSD Fisica Medica E Radioprotezione, Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCSU.O.S. Terapia Conservativa Della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro CuoreIstituto Di Fisiologia Clinica, Consiglio Nazionale Delle Ricerche (CNR)UOC Di Cardiologia, Dipartimento Di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, and Università Cattolica del Sacro CuoreUOC Di Medicina Nucleare, Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreCentro Malattie Endocrine E Metaboliche, Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro CuoreAbstract Objective Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF. Methods This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752). Results 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). Conclusions SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752https://doi.org/10.1186/s12933-022-01607-4DiabetesMetabolismMyocardial blood flowPerfusionPETSGLT-2 |
| spellingShingle | Lucia Leccisotti Francesca Cinti Gian Pio Sorice Domenico D’Amario Margherita Lorusso Maria Angela Guzzardi Teresa Mezza Shawn Gugliandolo Camilla Cocchi Umberto Capece Luca Indovina Pietro Manuel Ferraro Patricia Iozzo Filippo Crea Alessandro Giordano Andrea Giaccari Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report Cardiovascular Diabetology Diabetes Metabolism Myocardial blood flow Perfusion PET SGLT-2 |
| title | Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report |
| title_full | Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report |
| title_fullStr | Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report |
| title_full_unstemmed | Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report |
| title_short | Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report |
| title_sort | dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes the dapaheart trial a preliminary report |
| topic | Diabetes Metabolism Myocardial blood flow Perfusion PET SGLT-2 |
| url | https://doi.org/10.1186/s12933-022-01607-4 |
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