Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes

McGuire, Darren K.; Shih, Weichung J.; Cosentino, Francesco; Charbonnel, B.; Cherney, David Z.I.; Dagogo‐Jack, Samuel; Pratley, Richard E.; Greenberg, Michelle; Wang, Shuai; Huyck, Susan; Gantz, Ira; Terra, Steven G.; Masiukiewicz, Urszula; Cannon, Christopher P.

doi:10.1001/jamacardio.2020.4511

Cited by 657 publications

(533 citation statements)

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“…Ertugliflozin reduced risk for first HHF, for total HHF, and for total HHF/CV death events in patients with T2DM in the VERTIS CV trial, findings consistent with those reported for other members of the SGLT2 inhibitor class, 10 – 13 , 23 and provide additional supportive evidence for the use of SGLT2 inhibition in patients with T2DM to prevent HF-related outcomes.…”

Section: Discussionsupporting

confidence: 79%

“…To date, although CV outcome trials with SGLT2 inhibitors in patients with T2DM have shown heterogeneous results with regard to the effects on CV death (HRs ranging from 0.62 to 0.98), there has been remarkable consistency in the observed reduction in risk for first event of HHF across these trials, with HRs ranging from 0.61 to 0.73. 23 In VERTIS CV, the magnitude and timing of the reduction in risk of HHF, with consistent demonstration of an early benefit after study drug initiation, and the consistency of effect between doses correspond to what has been reported for other members of the SGLT2 inhibitor class in patients with T2DM and different levels of CV risk (with and without ASCVD). 10 , 12 , 13 Similar findings have been reported in trial populations with albuminuric diabetic kidney disease, 11 and with HF and reduced EF with or without T2DM.…”

Section: Discussionsupporting

confidence: 78%

“…The overall results of VERTIS CV together with the recently published meta-analysis indicate that the effect of ertugliflozin on HHF in patients with T2DM with ASCVD is consistent with that found across the class of SGLT2 inhibitors. 9 , 23 In the current prespecified analyses, we report more detailed data with ertugliflozin on HF-related outcomes. In comparison with other recent SGLT2 inhibitor CV outcome trials in patients with T2DM, the VERTIS CV population included the largest proportion of patients with a history of HF, 23.7% of the overall trial population, similar to the proportion found in a typical diabetes clinical practice (20%–30%).…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of Ertugliflozin on Heart Failure–Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease

et al. 2020

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Background: In patients with type 2 diabetes mellitus (T2DM), sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes. Methods: VERTIS CV, a double-blind, placebo-controlled trial, randomized patients with T2DM and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg or placebo. Prespecified secondary analyses compared ertugliflozin (pooled doses) versus placebo on time to first event of HHF and composite of HHF/CV death, overall and stratified by prespecified characteristics. Cox proportional hazard modeling was used with the Fine and Gray method to account for competing mortality risk, and Andersen-Gill modeling to analyze total (first+recurrent) HHF and total HHF/CV death events. Results: 8246 patients were randomized to ertugliflozin (n=5499) or placebo (n=2747); n=1958 (23.7%) had a history of heart failure (HF) and n=5006 (60.7%) had pre-trial ejection fraction (EF) available, including n=959 with EF≤45%. Ertugliflozin did not significantly reduce first HHF/CV death (HR, 0.88; 95% CI, 0.75, 1.03). Overall, ertugliflozin reduced risk for first HHF (HR, 0.70; 95% CI, 0.54, 0.90; P =0.006). Prior HF did not modify this effect (HF: HR, 0.63; 95% CI, 0.44, 0.90; no HF: HR, 0.79; 95% CI, 0.54, 1.15; P interaction=0.40). In patients with HF, the risk reduction for first HHF was similar for those with reduced EF≤45% vs preserved EF>45% or unknown. However, in the overall population, the risk reduction tended to be greater for those with EF≤45% (HR, 0.48; 95% CI, 0.30, 0.76) versus EF>45% (HR, 0.86; 95% CI, 0.58, 1.29). Effect on risk for first HHF was consistent across most subgroups, but greater benefit of ertugliflozin was observed in three populations with baseline eGFR<60mL/min/1.73m 2 , albuminuria, and diuretic use (each P interaction<0.05). Ertugliflozin reduced total events of HHF (RR, 0.70; 95% CI, 0.56, 0.87) and total HHF/CV death (RR, 0.83; 95% CI, 0.72, 0.96). Conclusions: In patients with T2DM with or without baseline HF, ertugliflozin reduced risk for first and total HHF and total HHF/CV death, adding further support for the use of SGLT2 inhibitors in primary and secondary prevention of HHF. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01986881

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of Ertugliflozin on Heart Failure–Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease

et al. 2020

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“…Their use in the highest risk class does not appear completely justified when compared with the underutilization of some pharmacological classes with proven cardiovascular benefit (i.e. GLP1-RA and SGLT2-i) [ 18 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study

Pintaudi

Scatena

Piscitelli

et al. 2021

Cardiovasc Diabetol

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Background The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.

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“…A patient or a provider may value one death/HHF event averted, to be almost five times (since [24.7-19.3 Several meta-analyses about the effects of SGLT2i were published in late 2019 and early 2020 19,[22][23][24][25][26][27] with different focus (e.g., cardiovascular or renal outcomes or safety) and different search strategies than our own. The strengths of the present meta-analysis are the simultaneous consideration of a broad range of both efficacy AND safety outcomes, the inclusion of four large studies and our focus on an expanded population of patients of extremely high cardiorenal risk.…”

Section: Discussionmentioning

confidence: 99%

The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now

Johansen

Argyropoulos

2020

Clinical Cardiology

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Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5 years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of the evidence. SGLT2i improve cardiorenal outcomes and have a beneficial risk benefit ratio across populations with cardiovascular disease, HFrEF and kidney disease. In this quantitative review, we synthesize the data from the large outcomes trials about the benefits and risks of SGLT2i. SGLT2i reduce all cause, cardiovascular mortality, heart failure hospitalizations, need for dialysis and acute kidney injury as a class effect across a broad range of populations with diabetes Type 2 at risk for cardiovascular disease, patients with HFrEF or CKD with or without diabetes. While certain adverse events for example, diabetic ketoacidosis and genital mycotic infections are reproducibly increased by SGLT2i, the absolute increase in the risk of these complications is smaller than the absolute risk reductions conferred by SGLT2i. Other complications such as amputations, fractures and urinary tract infections are increased to a lesser degree, or not at all (e.g., hypoglycemia). Overall, SGLT2is appear to have a favorable safety profile and thus should be used by cardiologists, nephrologists, endocrinologists, primary care physicians when managing the cardiorenal risk of their patients.

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Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes

Cited by 657 publications

References 46 publications

Efficacy of Ertugliflozin on Heart Failure–Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease

Efficacy of Ertugliflozin on Heart Failure–Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study

The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now

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