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

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.

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Heart failure hospitalisation relative to major atherosclerotic events in type 2 diabetes with versus without chronic kidney disease: a meta-analysis of cardiovascular outcomes trials

Diabetes & Metabolism ◽

10.1016/j.diabet.2021.101249 ◽

2021 ◽

pp. 101249

Author(s):

Julian W. Sacre ◽

Dianna J. Magliano ◽

Jonathan E. Shaw

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Heart Failure Hospitalisation

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Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses from the FIGARO-DKD Trial

Circulation ◽

10.1161/circulationaha.121.057983 ◽

2021 ◽

Author(s):

Gerasimos Filippatos ◽

Stefan D. Anker ◽

Rajiv Agarwal ◽

Luis M. Ruilope ◽

Peter Rossing ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Lower Risk ◽

Cardiovascular Death ◽

History Of ◽

The Impact ◽

New Onset

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD assessed the impact of finerenone on clinically important HF outcomes. Methods: Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m 2 , or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m 2 ,), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first event outcomes included: new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI 0.50-0.93]; P =0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including a 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI 0.70-0.95]; P =0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI 0.56-0.90]; P =0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52- 0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF.

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Do four SGLT2 inhibitors lead to different cardiorenal benefits in type 2 diabetes, in chronic heart failure, and in chronic kidney disease?

European Journal of Internal Medicine ◽

10.1016/j.ejim.2021.01.009 ◽

2021 ◽

Author(s):

Mei Qiu ◽

Liang-Liang Ding ◽

Ze-Lin Zhan ◽

Hai-Rong Zhou

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Chronic Heart Failure ◽

Kidney Disease ◽

Sglt2 Inhibitors

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Sodium-glucose cotransporter 2 inhibitor effects on cardiovascular outcomes in chronic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz292 ◽

2020 ◽

Vol 35 (Supplement_1) ◽

pp. i43-i47 ◽

Cited By ~ 1

Author(s):

Oshini Shivakumar ◽

Naveed Sattar ◽

David C Wheeler

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Major Adverse Cardiovascular Event ◽

Sglt2 Inhibitors ◽

Adverse Cardiovascular Event ◽

Sodium Glucose Cotransporter ◽

Patients With Heart Failure

Abstract Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events, specifically those related to heart failure in patients with type 2 diabetes. Reductions in major adverse cardiovascular event (MACE) outcomes are also observed, but confined largely to patients who have prior cardiovascular disease. Cardiovascular outcome benefits extend to patients with type 2 diabetes and reduced estimated glomerular filtration (eGFR) rate down to 30 mL/min/1.73 m2 and to patients with heart failure but without diabetes. Ongoing trials are exploring whether patients with chronic kidney disease (CKD) but without diabetes will gain similar benefits from this class of agents. Although some safety concerns have emerged, it seems likely that SGLT2 inhibitors will be used more widely in CKD patients to reduce their cardiovascular risk.

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Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction

Circulation ◽

10.1161/circulationaha.119.040144 ◽

2019 ◽

Vol 140 (12) ◽

pp. 1004-1014 ◽

Cited By ~ 17

Author(s):

Brian A. Bergmark ◽

Deepak L. Bhatt ◽

Darren K. McGuire ◽

Avivit Cahn ◽

Ofri Mosenzon ◽

...

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Type 2 Diabetes Mellitus ◽

Kidney Disease ◽

Cardiovascular Death ◽

Inverse Probability ◽

All Cause Mortality

Background: Metformin is first-line therapy for type 2 diabetes mellitus, although its effects on the cardiovascular system are unproved. Methods: In this post hoc analysis, patients in SAVOR-TIMI 53 (Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus) with baseline biomarker samples (n=12 156) were classified as ever versus never taking metformin during the trial period. Associations between metformin exposure and outcomes were estimated with inverse probability of treatment weighting Cox modeling for the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke, as well as cardiovascular death and all-cause mortality, with biomarkers included as covariates. Additional sensitivity analyses included propensity score matching and Cox multivariable models. Results: Of the 12 156 patients with baseline biomarker samples, 8971 (74%) had metformin exposure, 1611 (13%) had prior heart failure, and 1332 (11%) had at least moderate chronic kidney disease (estimated glomerular filtration rate ≤45 mL·min −1 ·1.73 m −2 ). Metformin use was associated with no difference in risk for the composite end point (hazard ratio for inverse probability of treatment weighting, 0.92 [95% CI, 0.76–1.11]) but lower risk of all-cause mortality (hazard ratio for inverse probability of treatment weighting, 0.75 [95% CI, 0.59–0.95]). There was no significant relationship between metformin use and these end points in patients with prior heart failure or moderate to severe chronic kidney disease. Conclusions: In a cohort of 12 156 patients with type 2 diabetes mellitus and high cardiovascular risk, metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but not lower rates of the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. This association was most apparent in patients without prior heart failure or moderate to severe chronic kidney disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01107886.

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