Effect of empagliflozin on myocardial structure and function in patients with type 2 diabetes at high cardiovascular risk: the SIMPLE randomized clinical trial

Ersbøll, Mads; Jürgens, Mikkel; Hasbak, Philip; Kjær, Andreas; Wolsk, Emil; Zerahn, Bo; Brandt-Jacobsen, Niels H; Gæde, Peter; Rossing, Peter; Faber, Jens; Inzucchi, Silvio E.; Gustafsson, Finn; Schou, Morten; Kistorp, Caroline

doi:10.1007/s10554-021-02443-5

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…This meta‐analysis showed that SGLT2i treatment was significantly associated with a reduction in LVESV (−8.44 ml) and LVEDV (−9.13 ml), and an increase in LVEF (2.45%), compared with placebo or other antidiabetic agents 41 . Comparing the results of the present study with those of prior randomized clinical trials that have assessed LV volumes and function by transthoracic echocardiography, we found that our results on LV volumes are in agreement with those of some, 42,43 but not with other studies 44‐46 . Additionally, we found that empagliflozin treatment was associated with a numerical but not significant reduction in LVMI.…”

Section: Discussionsupporting

confidence: 75%

“…41 Comparing the results of the present study with those of prior randomized clinical trials that have assessed LV volumes and function by transthoracic echocardiography, we found that our results on LV volumes are in agreement with those of some, 42,43 but not with other studies. [44][45][46] Additionally, we found that empagliflozin treatment was associated with a numerical but not significant reduction in LVMI. Two prior studies examining the effects of SGLT2is on LV mass assessed by transthoracic echocardiography in patients with type 2 diabetes have shown a significant reduction in LVMI, 42,45 whereas another study failed to do so.…”

Section: Cardiac Geometry and Systolic Functionmentioning

confidence: 63%

“…Additionally, we found that empagliflozin treatment was associated with a numerical but not significant reduction in LVMI. Two prior studies examining the effects of SGLT2is on LV mass assessed by transthoracic echocardiography in patients with type 2 diabetes have shown a significant reduction in LVMI, 42,45 whereas another study failed to do so 44 . It is probable that these divergent results are a result of differences in the clinical features of the recruited patients (subjects without a history of coronary heart disease or HF vs. subjects with established CV disease), duration of type 2 diabetes and duration of treatment with SGLT2is between the studies.…”

Section: Discussionmentioning

confidence: 99%

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Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open‐label, crossover, active‐comparator FIORE trial

Succurro

Vizza

Papa

et al. 2022

Diabetes Obesity Metabolism

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Aim To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamic 18F‐fluorodeoxyglucose‐positron emission tomography (18F‐FDG‐PET) combined with euglycaemic‐hyperinsulinaemic clamp compared with glimepiride in patients with type 2 diabetes. Materials and Methods To further investigate the cardioprotective mechanism of sodium‐glucose co‐transporter‐2 inhibitors, we performed a 26‐week, randomized, open‐label, crossover, active‐comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamic 18F‐FDG‐PET combined with euglycaemic‐hyperinsulinaemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry and myocardial mechano‐energetic efficiency, as well as systolic and diastolic function by echocardiography. Results Compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference −6.07 [−8.59, −3.55] μmol/min/100 g; P < .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end‐systolic and end‐diastolic volumes, N‐terminal pro b‐type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano‐energetic efficiency, red blood cells, and haematocrit and haemoglobin levels. Conclusions The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate.

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Section: Discussionsupporting

confidence: 75%

Section: Cardiac Geometry and Systolic Functionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open‐label, crossover, active‐comparator FIORE trial

Succurro

Vizza

Papa

et al. 2022

Diabetes Obesity Metabolism

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show abstract

“…A total of 931 patients included in nine articles ( 9 – 11 , 14 – 19 ) documented the changes in LVMI data. The SGLT-2i group had a better effective LVMI reduction than the placebo group (SMD −0.25, 95% CI −0.38 to −0.12, I 2 = 0.0%, p = 0.000) ( Figure 3B ).…”

Section: Resultsmentioning

confidence: 99%

“…Five studies ( 11 , 14 , 16 , 18 , 19 ) regarded the LVEDV. A random-effect model revealed that the SGLT-2i group had a better effect in LVEDV reduction than the placebo group (SMD −0.19, 95% CI −0.36 to −0.01, I 2 = 62.3%, p = 0.035) ( Figure 5B ).…”

Section: Resultsmentioning

confidence: 99%

Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis

Wang

Zhong²,

Zhang³

et al. 2023

Front. Endocrinol.

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ObjectiveThis systematic review and meta-analysis was performed to compare the effect of sodium-glucose cotransporter protein-2 inhibitors (SGLT-2i) and placebo on left ventricular hypertrophy (LVH) in patients with type 2 diabetes.MethodRandomized controlled trials (RCTs) comparing the LVH parameters of SGLT-2i to placebo in patients with type 2 diabetes were included. Our primary outcomes were the changes in left ventricular mass (LVM) and left ventricular mass index (LVMI) from baseline to the study endpoint. Secondary outcomes were the changes in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early mitral inflow velocity to atrial inflow velocity (E/A). Summary odds ratios were estimated using a fixed-effect or random-effect model.ResultsA total of 11 articles were included. Data were extracted from 11 original studies matching our inclusion criteria. In our meta-analysis, there were significant improvement in LVM (SMD −0.23, 95% CI −0.44 to −0.02, I2 = 22.6%, p = 0.034), LVMI (SMD −0.25, 95% CI −0.38 to −0.12, I2 = 0.0%, p = 0.000), LVEDV (SMD −0.19, 95% CI −0.36 to −0.01, I2 = 62.3%, p = 0.035), and LVESV (SMD −0.21, 95% CI −0.39 to −0.04, I2 = 32.9%, p = 0.017) in the SGLT-2i group compared with the placebo group. Furthermore, no significant differences were found in LVEF (SMD 0.13, 95% CI 0.00 to 0.26, I2 = 0.0%, p = 0.050) and E/A (SMD −0.01, 95% CI −0.22 to 0.20, I2 = 0%, p = 0.908) between the two groups.ConclusionsThis meta-analysis confirmed the beneficial effects of SGLT-2i on reversal of left ventricular remodeling. The LVH regression was more pronounced in studies of type 2 diabetes patients receiving SGLT-2i than placebo.

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Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation

Filippatos

Farmakis

Butler

et al. 2023

European J of Heart Fail

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AimsAtrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF.Methods and resultsIn this pre‐defined secondary analysis of EMPEROR‐Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66–0.93] vs. 0.78 [0.64–0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57–0.94] vs. 0.72 [0.54–0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m2/year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF.ConclusionsIn patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.

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Effect of empagliflozin on myocardial structure and function in patients with type 2 diabetes at high cardiovascular risk: the SIMPLE randomized clinical trial

Cited by 13 publications

References 34 publications

Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open‐label, crossover, active‐comparator FIORE trial

Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open‐label, crossover, active‐comparator FIORE trial

Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis

Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation

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