scholarly journals Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Repeated Measures ◽  
Medical Information ◽  
Controlled Trial ◽  
Extracellular Volume ◽  
Cardiovascular Outcomes ◽  
Fluid Volume ◽  
The Body

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

scholarly journals Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

The Lancet ◽  
2018 ◽  
Vol 392 (10157) ◽  
pp. 1519-1529 ◽  
Author(s):  
Adrian F Hernandez ◽  
Jennifer B Green ◽  
Salim Janmohamed ◽  
Ralph B D'Agostino ◽  
Christopher B Granger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Controlled Trial ◽  
Cardiovascular Outcomes ◽  
Double Blind

scholarly journals Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population

2021 ◽  
Vol 9 (1) ◽  
pp. e001413
Author(s):  
Jonathan Yap ◽  
Kamalesh Anbalakan ◽  
Wan Ting Tay ◽  
Daniel Ting ◽  
Carol Yim Cheung ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glycemic Control ◽  
Microvascular Complications ◽  
Population Based ◽  
Cardiovascular Outcomes ◽  
Microvascular Complication ◽  
The Impact ◽  
Hba1c Levels

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05).ConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.

scholarly journals Metformin and N-terminal pro B-type natriuretic peptide in type 2 diabetes patients, a post-hoc analysis of a randomized controlled trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0247939
Author(s):  
Wiebe M. C. Top ◽  
Philippe Lehert ◽  
Casper G. Schalkwijk ◽  
Coen D. A. Stehouwer ◽  
Adriaan Kooy
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Natriuretic Peptide ◽  
Treatment Effect ◽  
Controlled Trial ◽  
Secondary Analysis ◽  
Initial Increase ◽  
Post Hoc Analysis ◽  
Post Hoc

Background Beyond antihyperglycemic effects, metformin may improve cardiovascular outcomes. Patients with type 2 diabetes often have an elevated plasma level of N-terminal pro B-type as a marker of (sub) clinical cardiovascular disease. We studied whether metformin was associated with a reduction in the serum level of N-terminal pro B-type natriuretic peptide (NT-proBNP) in these patients. Methods In the HOME trial 390 insulin-treated patients with type 2 diabetes were randomized to 850 mg metformin or placebo three times daily. Plasma samples were drawn at baseline, 4, 17, 30, 43 and 52 months. In a post-hoc analysis we analyzed the change in NT-proBNP in both groups. We used a longitudinal mixed model analysis adjusting for age, sex and prior cardiovascular disease. In a secondary analysis we assessed a possible immediate treatment effect post baseline. Results Metformin did not affect NT-proBNP levels over time in the primary analysis (-1% [95%CI -4;3, p = 0.62]). In the secondary analysis there was also no sustained time independent immediate treatment effect (initial increase of 17% [95%CI 4;30, p = 0.006] followed by yearly decrease of -4% [95%CI -7;0, p = 0.07]). Conclusions Metformin as compared to placebo did not affect NT-proBNP plasma levels in this 4.3-year placebo-controlled trial. Potential cardioprotective effects of metformin cannot be explained by changes in cardiac pressures or volumes to the extent reflected by NT-proBNP.

scholarly journals Influence of Bromocriptine Plus Metformin Treatment on Glycaemia and Blood Pressure in Patients with Type 2 Diabetes Mellitus

2018 ◽  
Vol 25 (1) ◽  
pp. 59-66
Author(s):  
Alfredo Briones-Aranda ◽  
Javier Ramírez-Carballo ◽  
Bernardo Alfredo Romero Gómez ◽  
Victor Manuel Vega Villa ◽  
Manuela Castellanos Pérez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Controlled Trial ◽  
Combined Therapy ◽  
The Body ◽  
Open Label ◽  
D2 Agonist

Abstract Background and aims: Bromocriptine is a dopaminergic (D2) agonist that has shown hypoglycemic and normotensive activity in preclinical and clinical studies. The main objective of this study was to investigate the effect of bromocriptine plus metformin on glycaemia and blood pressure in patients with type 2 diabetes mellitus (T2DM). Material and methods: An open-label randomised controlled trial was conducted for three months. It involved two groups (n=10), each containing 2 women and 8 men with an average age of 50 years. One group was given monotherapy (MT) with metformin (850 mg every 12 h) and the other combined therapy (CT) with the same dose of metformin plus an increasing dose of bromocriptine (from 1.25 mg per day to 2.5 mg per day). The parameters monitored were glycaemia, glycated hemoglobin (HbA1c), serum creatinine, blood pressure, and the body mass index. Results: CT was able to significantly decrease the level of glycaemia, HbA1c and diastolic blood pressure, whereas MT had no effect on any of the measured variables. Conclusions: The ability of CT with bromocriptine and metformin to control glycaemia and produce a normotensive effect reaffirms its advantages for controlling T2DM. Further research is needed to improve this therapeutic strategy.

scholarly journals Clusterin and Its Role in Insulin Resistance and the Cardiometabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Jennifer Wittwer ◽  
David Bradley
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
The Body ◽  
Atherogenic Dyslipidemia ◽  
Cardiometabolic Syndrome ◽  
Multiple Components ◽  
Prevalence Of Obesity ◽  
Resistance To Insulin

The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.

scholarly journals Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261986
Author(s):  
Ning Li ◽  
Guowei Zhou ◽  
Yawei Zheng ◽  
Dan Lv ◽  
Xiangjun Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Ejection Fraction ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Reduced Ejection Fraction ◽  
Stage 4

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

Sign in / Sign up

Export Citation Format

Share Document