Cardiovascular Outcomes and Risks After Initiation of a Sodium Glucose Cotransporter 2 Inhibitor

Udell, Jacob A.; Yuan, Zuyi; Rush, Toni; Sicignano, Nicholas; Galitz, Michael S; Rosenthal, Norman

doi:10.1161/circulationaha.117.031227

Cited by 203 publications

(156 citation statements)

References 23 publications

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“…[2][3][4] The SGLT2i appear to have particularly profound benefits in patients with established cardiovascular disease for reducing cardiovascular death and heart failure as well as adverse renal outcomes. Benefits have been reported in 2 completed randomized trials with consistent associations in observational studies, [2][3][4][5] including those reported by Udell et al 6 in this issue of Circulation. In contrast to the more consistent cardiovascular benefits described across these studies, however, is a finding isolated to the CANVAS trial (Canagliflozin Cardiovascular Assessment Study) showing an excess risk of amputation with canagliflozin.…”

supporting

confidence: 60%

“…They also stand in contrast to other recent studies that demonstrate consistency in cardiovascular and limb benefits for antithrombotic and lipid-lowering therapies. [7][8][9][10] In this context, the results from Udell et al 6 provide the greatest impact. In the study of >25 000 patients with type 2 diabetes mellitus and established cardiovascular disease, the authors observed a consistent 2-fold risk of below-the-knee amputation, with the greatest absolute risk in patients with established peripheral artery disease (PAD).…”

mentioning

confidence: 97%

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Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk

Bonaca

Beckman

2018

Circulation

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supporting

confidence: 60%

mentioning

confidence: 97%

Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk

Bonaca

Beckman

2018

Circulation

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“…In parallel with CVD‐REAL cohorts, additional population‐based studies investigated CV outcomes with SGLT2‐Is from US (vs. non‐gliflozin agents),14, 15 UK Health Improvement Network (vs. other glucose‐lowering drugs)16 and Swedish (DPP4‐Is or SGLT2‐Is compared with insulin)17 databases. Although definitions of outcomes as well as patients' characteristics vary across different studies, all consistently highlighted a significantly reduced risk of MACE and other CV endpoints, except for the US cohort on canagliflozin (Table 1).…”

Section: Overview Of Resultsmentioning

confidence: 99%

“…Apart from RCTs, three US observational cohort studies14, 24, 60 and two disproportionality analyses of international spontaneous reporting systems, namely, the FDA Adverse Event Reporting System (FAERS) and the WHO Vigibase,61, 62 provided conflicting results as to whether or not this adverse effect concerns all SGLT2‐Is 63. Another critical issue is the mechanistic basis of this side effect,64 and the multifactorial role of disease and comorbidities.…”

Section: Observational Findings: What's Missing?mentioning

confidence: 99%

“…An interesting observation from a US cohort14 is the possible modification by concomitant use of GLP‐1 receptor agonists, potentially mitigating the amputation risk associated with SGLT2‐Is. These observations corroborated the hypothesis that specific drug combinations may be associated with a lower rate of adverse events.…”

Section: Observational Findings: What's Missing?mentioning

confidence: 99%

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Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Raschi

Poluzzi

Fadini

et al. 2018

Diabetes Obesity Metabolism

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Sodium glucose co‐transporter‐2 inhibitors have attracted the interest of the scientific community following the results from dedicated cardiovascular outcome trials, which demonstrated remarkable reduction in all‐cause mortality and other cardiovascular (CV) endpoints with empagliflozin and canagliflozin. These impressive results raised further expectations on real world data from large observational cohort studies. They were designed to address the possible existence of a class effect, and the uncertainty on whether this benefit can be extended from secondary to primary CV prevention of patients with type 2 diabetes. In this review, we collated data from existing observational studies (including the celebrated CVD‐REAL cohorts) and critically appraised results and methodological issues with the aim of providing clinical insight, including unsettled aspects, and proposing a research agenda for future investigations.

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Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease

et al. 2022

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IMPORTANCEThe cardiovascular outcome in selected populations when sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are emerging as standard therapy is not clearly understood. It is important to learn the magnitude of cardiovascular benefit using SGLT2-Is across the select subgroups that include both sexes and multiple age and racial and ethnic groups. OBJECTIVESTo evaluate the association between use of SGLT2-Is and cardiovascular benefits in a prespecified group in a larger sample size using data obtained from randomized clinical trials. DATA SOURCESSearch of electronic databases PubMed, Google Scholar, Web of Science, and Cochrane from inception to January 10, 2021, with additional studies identified through conference papers and meeting presentations, ClinicalTrials.gov, and reference lists of published studies. STUDY SELECTION Placebo-controlled randomized clinical trials in which participants had atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD, diabetes, or heart failure and which reported the primary outcome were included in this study. Multicenter observational and nonobservational studies and those with different outcomes of interest were excluded. DATA EXTRACTION AND SYNTHESIS Medical Subject Heading search terms included SGLT2-I and multiple cardiovascular outcomes in different combinations. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The analysis of all outcomes was performed using a Mantel-Haenszel equation and the randomeffects model. MAIN OUTCOMES AND MEASURES Six efficacy outcomes of SGLT2-I use (cardiovascular deathand hospitalization for heart failure [HHF] as the primary outcome and major adverse cardiovascular event, HHF, cardiovascular death, acute myocardial infarction, and all-cause mortality as secondary outcomes), were evaluated. Subgroup analysis was performed for the primary outcome of cardiovascular death or HHF. Odds ratios (ORs) and 95% CIs were used to compare 2 interventions. RESULTSTen studies with 71 553 participants were included, among whom 39 053 received SGLT2-Is; among studies that reported these data, 28 809 were men and 15 655 were women (mean age, 65.2 [range, 61.9-70.0] years). Race and ethnicity were defined in the original trials and were categorized as Asian, Black, or other (6900 participants) and White (26 646 participants) for the purposes of this analysis (the category "other" was not specified consistently). In terms of age, 16 793 were younger than 65 years and 17 087 were 65 years or older. At a mean follow-up 2.3 (range, (continued) Key Points Question What is the updated magnitude of benefit associated with sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) on outcome of cardiovascular death or hospitalization for heart failure (HHF) in different select subgroups of patients? Findings This meta-analysis of 10 highquality randomized clinical trials (71 553 participants) found that use of SGLT2-Is was associated with lower occurrence of cardiovascular death...

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Cardiovascular Outcomes and Risks After Initiation of a Sodium Glucose Cotransporter 2 Inhibitor

Abstract: Supplemental Digital Content is available in the text.

Cited by 203 publications

References 23 publications

Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk

Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease

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