scholarly journals Effects of SGLT2 Inhibitors on Renal Outcomes in Patients With Chronic Kidney Disease: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Ning Li ◽  
Dan Lv ◽  
Xiangjun Zhu ◽  
Ping Wei ◽  
Yuan Gui ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Renal Outcomes ◽  
Underlying Diseases

Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear.Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function.Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) >300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR<60 mL/min/1.73 m2 (HR 0.70, [95% CI 0.58–0.83], I2 = 0.00%) and by 43% in patients with UACR > 300 mg/g (HR 0.57, [95% CI 0.48–0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR<60 mL/min/1.73 m2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51–1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38–0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR > 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR<60 mL/min/1.73 m2: HR 0.81, [95% CI 0.47–1.38], I2 = 0.00%; UACR > 300 mg/g: HR 0.66, [95% CI 0.41–1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48).Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.

scholarly journals Metabolic syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a post hoc analyses of the EMPA-REG OUTCOME trial

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
João Pedro Ferreira ◽  
Subodh Verma ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Sabine Lauer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Trial Registration ◽  
World Health ◽  
Atherosclerotic Cardiovascular Disease ◽  
Renal Outcomes ◽  
Outcome Trial

Abstract Background Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95% CI 1.01–2.98), heart failure hospitalization: HR = 2.64 (95% CI 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95% CI 2.17–4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. Conclusions A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Trial registration Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT 01131676

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.

scholarly journals Metabolic Syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: A post hoc analyses of the EMPA-REG OUTCOME trial

2020 ◽  
Author(s):  
João Pedro Ferreira ◽  
Subodh Verma ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Sabine Lauer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
World Health ◽  
Atherosclerotic Cardiovascular Disease ◽  
Mixed Effect ◽  
Renal Outcomes ◽  
Outcome Trial

Abstract Background: Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods: A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10mg or 25mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results: MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR=1.73 (95%CI=1.01-2.98), heart failure hospitalization: HR=2.64 (95%CI=1.22, 5.72), and new or worsening nephropathy: HR=3.11 (95%CI=2.17-4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS.Conclusions: A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS.

scholarly journals Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study

2021 ◽  
Author(s):  
Geert Goderis ◽  
Bert Vaes ◽  
Pavlos Mamouris ◽  
Eline van Craeyveld ◽  
Chantal Mathieu
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Primary Care ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Research Network ◽  
Blood Pressure Target ◽  
Atherosclerotic Cardiovascular Disease

Abstract Aims This study aims to assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and their combined presence in type 2 diabetes (T2D) patients in primary care for whom the 2019 ADA/EASD consensus update “Management of Hyperglycemia in Type 2 Diabetes” recommends GLP-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-I) as first-line medications after metformin. Methods Data were obtained in 2015 from Intego, a morbidity registration network of 111 general practitioners (GPs) working in 48 practices and including 123 261 registered patients. Results Of 123 261 patients, 9616 had T2D. Of these patients, 4200 (43.7%) presented with ASCVD and/or CKD and/or HF. Specifically, 3348 (34.8%) patients had ASCVD, 388 (4.0%) had heart failure, and 1402 (14.6%) had CKD. Compared to patients without any of these comorbidities, patients with at least 1 of these conditions were older (69.7 ±12.6 vs. 63.1±12.5 years), had higher LDL-C values (104.2±35.8 mg/dl vs. 97.2±37.7) and less frequently achieved the systolic blood pressure target of 140 mm Hg (53 vs. 61%) (all p<0.001). Comorbid patients also had significantly more other comorbidities, such as dementia or cancer; received more recommended medications, such as statins; and received less metformin. Most patients with HF (325; 3.4%) had ASCVD (114; 1.2%), CKD (76; 0.8%), or both (135; 1.4%). In total, 478 patients with CKD (5.0%) also had ASCVD. Conclusions At the primary care level, 44% of T2D patients suffer from ASCVD, CKD, and/or HF, and thus qualify for GLP-1RA or SGLT2-I therapy.

scholarly journals Metabolic Syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: A post hoc analyses of the EMPA-REG OUTCOME trial

2020 ◽  
Author(s):  
João Pedro Ferreira ◽  
Subodh Verma ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Sabine Lauer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
World Health ◽  
Atherosclerotic Cardiovascular Disease ◽  
Mixed Effect ◽  
Renal Outcomes ◽  
Outcome Trial

Abstract Background Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95%CI = 1.01–2.98), heart failure hospitalization: HR = 2.64 (95%CI = 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95%CI = 2.17–4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. Conclusions A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT 01131676.

scholarly journals Efficacy and renal outcomes of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease

2018 ◽  
Vol 131 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Michael S. Kelly ◽  
Jelena Lewis ◽  
Ashley M. Huntsberry ◽  
Lauren Dea ◽  
Ivan Portillo
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sglt2 Inhibitors ◽  
Renal Outcomes

scholarly journals The Effect of Long-term Sodium-glucose Cotransporter 2 Inhibitor Treatment on Renal Function in the Patients with Type 2 Diabetes

2020 ◽  
Vol 95 (4) ◽  
pp. 236-243
Author(s):  
Jong Ha Baek ◽  
Tae Jung Oh ◽  
Ju-Young Moon ◽  
Taehee Kim ◽  
Seung Hyu Ko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Renal Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Inhibitor Treatment

Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)

scholarly journals Effects of SGLT2 inhibitors on cardiovascular death and all-cause death in patients with type 2 diabetes and chronic kidney disease: an updated meta-analysis including the SCORED trial

2021 ◽  
Vol 12 ◽  
pp. 204201882110449
Author(s):  
Li-Min Zhao ◽  
Ze-Lin Zhan ◽  
Mei Qiu
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Ckd Progression ◽  
Meta Analyses

Background: The effects of sodium-glucose transporter 2 (SGLT2) inhibitors on cardiovascular death (CV death) and all-cause death (AC death) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are currently under intensive investigation. We intended to conduct an updated meta-analysis including the SCORED trial to evaluate the effects of SGLT2 inhibitors on death and cardiorenal events in this vulnerable population. Methods: Cardiorenal outcome trials of SGLT2 inhibitors were included. Primary outcomes were CV death and AC death, while secondary outcomes were hospitalization for heart failure (HHF), myocardial infarction (MI), CKD progression, cardiovascular death or hospitalization for heart failure (CV death or HHF), major adverse cardiovascular events (MACE), and stroke. Meta-analysis was conducted for each outcome. Results: Eight trials were included for meta-analysis. Compared with placebo, SGLT2 inhibitors significantly lowered the risk of CV death (HR = 0.86, 95% CI = 0.75–0.98), AC death (HR = 0.87, 95% CI = 0.79–0.96), HHF (HR = 0.64, 95% CI = 0.56–0.74), MI (HR = 0.76, 95% CI = 0.65–0.89), CKD progression (HR = 0.62, 95% CI = 0.54–0.72), and CV death or HHF (HR = 0.73, 95% CI = 0.67–0.80). No heterogeneity existed in the above meta-analyses (all I2 values = 0%), whereas moderate heterogeneity existed in the meta-analyses for MACE and stroke (I2 = 31.6% and 44.5%, respectively). Conclusions: Our findings suggest that SGLT2 inhibitors versus placebo significantly lower death, heart failure, renal failure, and MI events in patients with T2D and CKD. Head-to-head trials are needed to examine the possible differences in the effects of various gliflozins on MACE and stroke.

scholarly journals Empagliflozin and Cardio-renal Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease – Implications for Clinical Practice

2018 ◽  
Vol 14 (2) ◽  
pp. 40 ◽  
Author(s):  
David H Fitchett
Keyword(s):  
Type 2 Diabetes ◽  
Primary Outcome ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Outcome Study ◽  
Rapid Reduction ◽  
Renal Outcomes ◽  
Risk Of Progression ◽  
Cv Disease

In patients with type 2 diabetes (T2D), the excretion of glucose by the kidney with sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers glycosylated haemoglobin (HbA1c) levels, decreases body weight and visceral adiposity, as well as improving cardio-renal haemodynamics. Currently, four SGLT2 inhibitors are approved in the US and Europe to improve glycaemic control – empagliflozin, dapagliflozin, canagliflozin, and ertuglifozin. Recently, the SGLT2 inhibitor empagliflozin was approved by the FDA for the reduction of cardiovascular (CV) death in adults with T2D and CV disease (CVD). This approval was based on the findings of the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study, which was the first study to show a significant reduction of a primary CV endpoint with a glucose-lowering agent. In this study, the primary outcome (CV mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was reduced by empagliflozin (10.5%; 490/4,687) compared with placebo (12.1%; 282/2,333); hazard ratio (HR), 0.86 (95% confidence interval [CI]: 0.74, 0.99). The primary outcome was driven by a large reduction of CV mortality (relative risk reduction [RRR], 38%). Empagliflozin also reduced all-cause mortality (RRR, 32%). Furthermore, empagliflozin reduced the adjudicated outcome of heart failure (HF) hospitalisation by 35% (HR, 0.65; 95% CI: 0.50, 0.85). Other non-adjudicated measures of HF outcomes were similarly reduced including investigator reported HF, the introduction of loop diuretics and death from HF. In the analysis of renal outcomes, incident or worsening nephropathy was reduced for empagliflozin (12.7%) compared with placebo (18.8%); HR, 0.61 (95% CI: 0.53, 0.70). Empagliflozin significantly reduced the risk of progression to macroalbuminuria (38%) and doubling of creatinine (44%), as well as the need of starting renal-replacement therapy (55%). The benefits of empagliflozin for the reduction of CV death, all-cause death and hospitalisation for HF were observed across a range of baseline subgroups such as HbA1c level and renal function (down to estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m2). The rapid reduction of HF outcomes with empagliflozin is observed across the spectrum of CVD and HF risk and represents a therapeutic advance in the prevention and perhaps also in the treatment of HF, an often poorly recognised complication of T2D. This review discusses the EMPA-REG OUTCOME study and the implications for treating patients with T2D and CVD.

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