Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria – A double blind randomized placebo-controlled crossover trial

Eickhoff, Mie K.; Olsen, Flemming Javier; Frimodt‐Møller, Marie; Díaz, Lars Jorge; Faber, Jens; Jensen, Magnus Thorsten; Rossing, Peter

doi:10.1016/j.jdiacomp.2020.107590

Cited by 26 publications

(18 citation statements)

References 39 publications

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“…A total of 21 RCTs [10, 24, 25, 29-31, 33, 39-52] were recognized eligible in this meta-analysis, including 3 in crossover design [41,44,50]. A total of 10,978 participants were enrolled, including 6236 in the SGLT2i group and 4821 in the control group.…”

Section: Resultsmentioning

confidence: 99%

“…Participants with T2DM that were mostly in stage A-B HF were enrolled in 10 studies [24,25,39,40,44,46,48,49,51,52], and patients with T2DM and stage C HF were enrolled in 11 studies [10, 29-31, 33, 41-43, 45, 47, 50]. LVMI, LVEDVI, LVESVI, LAVI, LVEF, GLS, the E/e' ratio, plasma NT-proBNP level, and the KCCQ score were reported in 6 [24,25,29,44,45,52], 3 [25,29,30], 3 [25,29,30], 4 [25,29,45,52], 9 [24, 25, 29-31, 39, 40, 44, 45], 4 [24,39,44,51], 8 [24,25,30,31,44,45,49,52], 11 [10,24,25,31,41,[44][45][46]<...>…”

Section: Resultsmentioning

confidence: 99%

“…LVMI, LVEDVI, LVESVI, LAVI, LVEF, GLS, the E/e' ratio, plasma NT-proBNP level, and the KCCQ score were reported in 6 [24,25,29,44,45,52], 3 [25,29,30], 3 [25,29,30], 4 [25,29,45,52], 9 [24, 25, 29-31, 39, 40, 44, 45], 4 [24,39,44,51], 8 [24,25,30,31,44,45,49,52], 11 [10,24,25,31,41,[44][45][46][48][49][50] and 3 [10,42,43] studies, respectively. Cardiac structure and function were evaluated by magnetic resonance imaging in 4 studies [24,25,29,51], echocardiography in 8 studies [24,…”

Section: Resultsmentioning

confidence: 99%

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Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Zhao

Wang

et al. 2021

Cardiovasc Diabetol

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Background Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. Methods We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types. Results Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p = 0.01; I2 = 0%) in the overall population. Conclusion The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Zhao

Wang

et al. 2021

Cardiovasc Diabetol

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“…Both were prospective, double-blinded, placebo-controlled cross-over clinical trials designed to assess the albuminuria-lowering effects of dapagliflozin 10 mg/day. The study designs and primary outcomes of both clinical trials were published previously [10,11]. In short, the IMPROVE study enrolled 34 patients with type 2 diabetes, an HbA 1c level between 55 and 100 mmoL/moL, and a first morning void urinary albumin creatinine ratio (UACR) ≥100 mg/g and <3500 mg/g from the Department of Internal Medicine Ziekenhuisgroep Twente, the Netherlands.…”

Section: Methodsmentioning

confidence: 99%

Effects of Dapagliflozin on Volume Status When Added to Renin–Angiotensin System Inhibitors

Eickhoff

Dekkers

Kramers

et al. 2019

JCM

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Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart and kidney failure in patients with type 2 diabetes, possibly due to diuretic effects. Previous non-placebo-controlled studies with SGLT2 inhibitors observed changes in volume markers in healthy individuals and in patients with type 2 diabetes with preserved kidney function. It is unclear whether patients with type 2 diabetes and signs of kidney damage show similar changes. Therefore, a post hoc analysis was performed on two randomized controlled trials (n = 69), assessing effects of dapagliflozin 10 mg/day when added to renin–angiotensin system inhibition in patients with type 2 diabetes and urinary albumin-to-creatinine ratio ≥30 mg/g. Blood and 24-h urine was collected at the start and the end of treatment periods lasting six and 12 weeks. Effects of dapagliflozin compared to placebo on various markers of volume status were determined. Fractional lithium excretion, a marker of proximal tubular sodium reabsorption, was assessed in 33 patients. Dapagliflozin increased urinary glucose excretion by 217.2 mmol/24 h (95% confidence interval (CI): from 155.7 to 278.7, p < 0.01) and urinary osmolality by 60.4 mOsmol/kg (from 30.0 to 90.9, p < 0.01), compared to placebo. Fractional lithium excretion increased by 19.6% (from 6.7 to 34.2; p < 0.01), suggesting inhibition of sodium reabsorption in the proximal tubule. Renin and copeptin increased by 46.9% (from 21.6 to 77.4, p < 0.01) and 33.0% (from 23.9 to 42.7, p < 0.01), respectively. Free water clearance (FWC) decreased by −885.3 mL/24 h (from −1156.2 to −614.3, p < 0.01). These changes in markers of volume status suggest that dapagliflozin exerts both osmotic and natriuretic diuretic effects in patients with type 2 diabetes and kidney damage, as reflected by increased urinary osmolality and fractional lithium excretion. As a result, compensating mechanisms are activated to retain sodium and water.

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“…The trial was conducted between 1 August 2015 and 5 July 2017 in Copenhagen, Denmark. The study design has been described before ( Eickhoff et al, 2020 ) and a complete list of inclusion and exclusion criteria can be found in Supplementary Table S2 . In short, participants were eligible if they had type 2 diabetes, an estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73 2 , HbA1c > 58 mmol/mol (7.5%), and UACR ≥30 mg/g in two out of three consecutive first morning void urine samples.…”

Section: Methodsmentioning

confidence: 99%

Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor

et al. 2022

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Background: Elevated soluble urokinase plasminogen activator receptor (suPAR) is highly associated with increased risk of diabetic complications. Dapagliflozin is a drug inhibiting the sodium-glucose co-transporter 2 in the kidney to decrease blood glucose, while also decreasing risk of kidney disease, heart failure, and death. Therefore, we have investigated suPAR as a monitor for treatment effect with dapagliflozin in diabetes.Methods: suPAR was measured in two double-blinded randomized clinical cross-over trials. The first trial investigated the effect of a single dose dapagliflozin 50 mg or placebo 12 h after intake, in individuals with type 1 diabetes and albuminuria. The second trial investigated the effect of a daily dose dapagliflozin 10 mg or placebo for 12 weeks, in individuals with type 2 diabetes and albuminuria. suPAR was measured in serum samples taken, in the acute trial, after treatment with dapagliflozin and placebo, and in the long-term trial, before and after treatment with dapagliflozin and placebo. Effect of dapagliflozin on suPAR levels were assessed using paired t-test.Results: 15 participants completed the acute trial and 35 completed the long-term trial. Mean difference in suPAR between dapagliflozin and placebo in the acute trial after 12 h was 0.70 ng/ml (95% CI: 0.66; 1.33, p = 0.49). In the long-term trial the mean difference was 0.06 ng/ml (95% CI -0.15; 0.27, p = 0.57).Conclusion: Based on our findings we conclude that suPAR is not a feasible marker to monitor the effect of treatment with dapagliflozin. Thus, a further search of suitable markers must continue.

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Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria – A double blind randomized placebo-controlled crossover trial

Cited by 26 publications

References 39 publications

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Effects of Dapagliflozin on Volume Status When Added to Renin–Angiotensin System Inhibitors

Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor

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