Sie können Operatoren mit Ihrer Suchanfrage kombinieren, um diese noch präziser einzugrenzen. Klicken Sie auf den Suchoperator, um eine Erklärung seiner Funktionsweise anzuzeigen.
Findet Dokumente, in denen beide Begriffe in beliebiger Reihenfolge innerhalb von maximal n Worten zueinander stehen. Empfehlung: Wählen Sie zwischen 15 und 30 als maximale Wortanzahl (z.B. NEAR(hybrid, antrieb, 20)).
Findet Dokumente, in denen der Begriff in Wortvarianten vorkommt, wobei diese VOR, HINTER oder VOR und HINTER dem Suchbegriff anschließen können (z.B., leichtbau*, *leichtbau, *leichtbau*).
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a class of medications initially developed for glycemic control in type 2 diabetes mellitus (T2DM) but found to have broader cardiometabolic impacts. In this review, we discuss the proposed mechanisms of action of SGLT2i and review important trials that have demonstrated improvements in cardiovascular outcomes. SGLT2i have demonstrated benefits in the treatment of major categories of cardiovascular disease (CVD) and have been shown to reduce major adverse cardiovascular events (MACE) in patients with diabetes and CVD or renal disease. Findings have been translated into recommendations in clinical guidelines by the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and American Diabetes Association (ADA). It is important to consider a patient’s comorbid conditions, as well as potential medication side effects, prior to initiating SGT2i. While large trials have established the cardiovascular (CV) and renal benefits of SGLT2i, a number of studies are now exploring their role in acute care settings and novel patient populations.
Key Summary Points
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a class of therapies developed to improve glycemic control in type 2 diabetes mellitus (T2DM) with growing evidence of their beneficial cardiometabolic effects.
There are several proposed cardiometabolic mechanisms of SGLT2i, including, but not limited to, improvement in hemodynamics, prevention of remodeling, and anti-inflammatory effects.
SGLT2i reduce major adverse cardiovascular events (MACE) and are effective therapeutic agents for managing heart failure (HF).
SGLT2i are considered one of the pillars of guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF)
SGLT2i are available in oral formulations, and careful patient selection based on available clinical data is essential to optimize outcomes. It is important to be mindful of estimated glomerular filtration rate (eGFR) thresholds prior to starting a patient on an SGLT2i.
Introduction
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are transformative oral agents first developed to improve glycemic control by blocking renal glucose reabsorption. Landmark trials have shown reductions in major adverse cardiovascular events (MACE) across multiple populations with type 2 diabetes (T2DM), chronic kidney disease (CKD), and heart failure (HF), regardless of ejection fraction or diabetic status. This review synthesizes emerging evidence for SGLT2i in HF, CKD, hypertension (HTN), and atrial fibrillation (AF). Finally, this review describes the practical considerations of incorporating SGLT2i into guideline-directed cardiovascular (CV) care.
Anzeige
Methods
We conducted a PubMed search for studies published before March 2025 that evaluated CV outcomes associated with SGLT2i. Search terms included “SGLT2 inhibitor,” “sodium-glucose cotransporter-2,” and specific agents such as “dapagliflozin” and “empagliflozin,” in combination with CV terms like “major adverse cardiovascular events,” “coronary artery disease,” “heart failure,” “hypertension,” “chronic kidney disease,” and “atrial fibrillation.” Studies were included if they reported clinical endpoints related to MACE, coronary artery disease (CAD), HF, HTN, CKD, or AF in adult populations treated with SGLT2i. Non-human studies and case reports were excluded. Relevant data on CV outcomes, study design, and patient characteristics were extracted from the final set of included trials and observational studies.
Ethical Approval
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
Mechanisms of Risk Reduction
There are six sodium-glucose co-transporter proteins identified in the human body, and each binds sugar differently. Among these is the SGLT2 protein, which is predominantly expressed in the proximal convoluted tubules of the kidneys. Approximately 80–90% of filtered glucose reabsorption is accounted for by SGLT2. Inhibition of SGLT2 causes an increase in the excretion of glucose through the urine while also inhibiting glucose reabsorption into the renal tubule [1].
Cardiovascular disease (CVD) is thought to arise from various factors, including metabolic stresses, cardiac and vascular dysfunction, impaired angiogenesis, and the progression of atherosclerosis. In relation to these drivers of CVD, SGLT2i may provide benefits through several proposed mechanisms (Fig. 1). While SGLT2i are known to improve ventricular loading conditions via their diuretic and natriuretic effects, studies suggest they may also improve cardiac metabolism by shifting the heart’s fuel preference towards more efficient substrates like ketone bodies. This is thought to improve cardiac output and mechanical efficiency while reducing lipotoxicity and improving mitochondrial function. SGT2i may also play a role in reducing cardiac fibrosis by activating M2 macrophages, thereby suppressing differentiation of myofibroblasts. Studies have also demonstrated a possible direct effect of SGLT2i on cytosolic sodium and calcium levels via inhibition of the Na+/H+ exchanger 1 isoform within the myocardium. This in turn may result in improved cardiac function in patients with heart failure. Several mechanisms have also been proposed for possible anti-inflammatory effects of SGLT2i [2, 3].
Despite a wealth of experimental data regarding cardioprotective mechanisms of SGLT2i, key questions remain regarding their effects on cardiac remodelling, serum biomarkers, and arrhythmias with ongoing trials aiming to provide clearer insights into these areas and their potential role in treating heart disease [3].
Cardiovascular Outcomes
This section reviews current evidence regarding SGLT2i effects on MACE, HF, HTN, AF, and CKD, with detailed findings of trials discussed in Tables 1 and 2.
Table 1
Populations of interest and duration of follow-up for included SGLT2i studies
Study
Year
Population
Follow-up (months)
Primary outcome(s)
Empaglifozin
EMPA-REG OUTCOMEa
2015
T2DM with established CVD
37
Composite of CV death, non-fatal MI, or non-fatal stroke
EMPA REG-BPa
2018
T2DM with HTN
3
Change in 24-h systolic and diastolic BP
EMPA-RESPONSE-AHFa
2019
Hospitalized ADHF
2
Composite of worsening HF, rehospitalization, and death
EMPEROR-Reduceda
2020
HFrEF (LVEF < 40%), with or without T2DM
16
Composite of CV death or HHF
EMPEROR-Preserveda
2021
HFpEF (LVEF > 40%), with or without T2DM
26
Composite of CV death or HHF
EMPA-HFa
2021
HF (LVEF > 40%), with NT-proBNP > 300 or patients with AF and NT-proBNP > 900
2
Safety, renal function, diuresis
EMPULSEa
2022
Hospitalized ADHF
3
Clinical benefit (KCCQ score), symptoms
EMPA-Kidneya
2023
CKD
24
Composite of CKD progression or death from CV causes
Dapaglifozin
DECLARE-TIMI 58a
2019
T2DM with ASCVD or multiple risk factors
50.4
Co-primary: MACE; CV death or HHF
DAPA-HFa
2019
HFrEF (LVEF < 40%), with or without T2DM
18
Composite worsening HF or CV death
DAPA-CKDa
2020
CKD
28.8
Composite of decline in eGFR, ESKD, or death from renal or CV causes
Canagliflozin
CANVAS Programa
2017
T2DM at high CV risk
43.3
Composite of CV death, non-fatal MI, or non-fatal stroke
CREDENCEa
2019
T2DM with CKD
31
Composite of ESKD, doubling CR, or death from renal or CV causes
CANA-HFa
2023
T2DM with chronic HFrEF
3
Co-primary: Peak VO2; VE/VCO2 slope
Sotagliflozin
SCOREDa
2021
T2DM with CKD and additional risk factors
16
MACE
SOLOIST-WHFa
2021
T2DM with HHF
9
Composite of CV death, HHF, urgent HF visits
Other SGLT2i or SGLT2i class
VERTIS-CVa
2020
T2DM with established ASCVD
42
Composite of CV death, non-fatal MI, or non-fatal stroke
Fernandes et al.b
2021
T2DM or HF
19
Atrial arrhythmia, SCD, ventricular arrhythmia
SGLT2-I AMI PROTECT Registryc
2022
T2DM hospitalized for acute MI
24
MACE and HHF
Abu-Qaoud et al.c
2023
T2DM undergoing AF ablation
12
AF recurrence (cardioversion, antiarrhythmic use, repeat ablation)
Liao et al.b
2024
T2DM, HF, and/or CKD
17
AF, atrial arrhythmia, SCD, ventricular arrhythmia
T2DM type 2 diabetes mellitus, CVD cardiovascular disease, CV cardiovascular, MI myocardial infarction, ASCVD atherosclerotic cardiovascular disease, HHF hospitalization for heart failure, MACE major adverse cardiovascular events, HF heart failure, HFrEF heart failure with reduced ejection fraction, LVEF left ventricular ejection fraction, HFpEF heart failure with preserved ejection fraction, CKD chronic kidney disease, ESKD end-stage kidney disease, ADHF acute decompensated heart failure, KCCQ Kansas City Cardiomyopathy Questionnaire, HTN hypertension, BP blood pressure, AF atrial fibrillation, SCD sudden cardiac death, VO2 maximal oxygen uptake, VE/VCO2 ventilation efficiency, NT-proBNP N-terminal prohormone of brain natriuretic peptide, eGFR estimated glomerular filtration rate
aRandomized control trial
bMeta-analysis
cObservational study
Table 2
Summary of key cardiovascular outcomes from included studies
Study
Medication
Outcome of interest
Observed difference (95% CI)
MACE
EMPA-REG OUTCOME
Empagliflozin
MACE (HR)
0.86 (0.74–0.99)*
DAPA-HF
Dapagliflozin
MACE (HR)
0.82 (0.69–0.98)*
DECLARE-TIMI 58
Dapagliflozin
MACE (HR)
0.93 (0.84–1.03)
CREDENCE
Canagliflozin
MACE (HR)
0.80 (0.67–0.95)*
CANVAS
Canagliflozin
MACE (HR)
0.86 (0.75–0.97)*
SCORED
Sotagliflozin
MACE (HR)
0.84 (0.72–0.99)*
VERTIS CV
Ertugliflozin
MACE (HR)
0.97 (0.85–1.11)
SGLT2-I AMI PROTECT
Any SGLT2i
MACE (HR)
0.57 (0.33–0.99)*
Heart failure
EMPEROR-Reduced
Empagliflozin
Worsening HF or CV death (HR)
0.75 (0.65–0.86)*
EMPEROR-Preserved
Empagliflozin
Worsening HF or CV death (HR)
0.79 (0.69–0.90)*
EMPA-REG OUTCOME
Empagliflozin
HHF or CV death (HR)
0.66 (0.55–0.79)*
EMPA-RESPONSE-AHF
Empagliflozin
Worsening HF, rehospitalization, death within 60 days (percent)
Large-scale clinical trials have shown that some SGLT2i reduce MACE in patients with T2DM, particularly those with established CV or renal disease.
The EMPA-REG OUTCOME trial showed a significant reduction in MACE with empagliflozin, driven by a reduction in the risk of CV death among patients with T2DM and established CVD [4]. The CANVAS Program also found reductions in CV death and nonfatal MI with canagliflozin, though not in nonfatal stroke [5]. In the DAPA-HF trial, dapagliflozin reduced CV death and showed favorable trends in MACE despite not being powered for this composite [9]. This was further explored with the DECLARE-TIMI 58 trial found that dapagliflozin did not significantly lower MACE overall, but did reduce hospitalizations for HF and improve renal outcomes [6]. Similarly, the VERTIS-CV trial confirmed the CV safety of ertugliflozin but showed no significant superiority in MACE outcomes [7]. Real-world data from the SGLT2-I AMI PROTECT Registry support these findings, showing a significant reduction in MACE in patients with T2DM hospitalized for MI and treated with SGLT2i [8].
Additional CV outcomes trials, although primarily focused on HF endpoints, offer further insight into MACE outcomes. Empagliflozin significantly reduced the combined risk of CV death or hospitalization for HF in patients with heart failure with reduced ejection fraction (HFrEF). However, the reduction in CV death alone was not statistically significant [10].
SGLT2i have also been studied in patients with CKD and other high-risk groups. The CREDENCE trial, though focused on renal endpoints, found a significant reduction in MACE with canagliflozin in patients with diabetic kidney disease [11]. This trial was important because it confirmed that SGLT2i could reduce CV risk in patients with advanced diabetic kidney disease. Similarly, the SCORED trial, which enrolled patients with T2DM and CKD, observed a significant reduction in MACE, though this was no longer the primary endpoint at study conclusion [12].
While not all SGLT2i have indicated uniform effects on MACE, the overall evidence supports a clinically meaningful reduction in CV events, especially in patients with T2DM and established CV or renal disease. Whether SGLT2i reduce single endpoints like MI, or more specifically ST-segment elevation MI (STEMI), is a topic of ongoing research. Some of the challenges to this include competing background therapies in populations of interest, diversity of MI subtypes, and overall time-course of atherosclerotic disease progression. Nonetheless, consistent trends in CV death and MI across multiple studies suggest that SGLT2i may contribute to broader cardioprotection in appropriately selected patients.
Key Point: Large-scale clinical trials have shown that some SGLT2i reduce MACE in patients with T2DM, particularly those with established CV or renal disease.
Anzeige
Heart Failure: Outpatient
The role of SGLT2i in HF has been extensively studied across a spectrum of patient populations, including those with and without T2DM and across both reduced and preserved ejection fraction phenotypes. Initial CV outcome trials such as EMPA-REG OUTCOME and DECLARE-TIMI 58 provided important insights, showing significant reductions in hospitalization for HF among patients with T2DM at high CV risk treated with empagliflozin and dapagliflozin, respectively [4, 6].
Subsequent trials directly targeting patients with established HF further clarified their therapeutic role. The DAPA-HF trial demonstrated a significant relative risk reduction in the composite outcome of worsening HF or CV death with dapagliflozin in patients with HFrEF, regardless of diabetes status [9]. Similarly, the EMPEROR-Reduced trial showed a significant reduction in this same composite outcome with empagliflozin in patients with HFrEF, alongside significant renal benefits [13]. These findings solidified SGLT2i as a cornerstone therapy in HFrEF management.
In patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF and HFpEF), the EMPEROR-Preserved trial was the first to demonstrate a significant relative risk reduction in the composite of CV death or HF hospitalization with empagliflozin [10]. More recently, the DELIVER trial expanded these benefits to patients with HFmrEF and HFpEF with dapagliflozin [14]. These findings suggest the effects of SGLT2i in reducing HF morbidity extend across a broad range of HF phenotypes.
Sotagliflozin, a dual SGLT1/SGLT2 inhibitor, has also demonstrated efficacy in HF. In the SOLOIST-WHF trial, patients with T2DM and recently decompensated HF treated with sotagliflozin had a significantly reduced risk of CV death and hospitalizations [15]. Notably, sotagliflozin is now approved in the USA for HF, with proposed mechanisms that extend beyond natriuresis, including modulation of intestinal glucose absorption and improved cardiac metabolism.
Anzeige
Key Point: Large-scale clinical trials have shown that SGLT2i reduce rates of CV death and HF hospitalizations in patients with HF regardless of ejection fraction or glycemic status.
Heart Failure: Inpatient
SGLT2i in the inpatient management of acute decompensated heart failure (ADHF) continues to be an area of growing clinical interest. While clinical data regarding SGLT2i use in cardiogenic shock is limited, many recent trials have explored safety and efficacy of starting SGLT2i during in patients hospitalized for HF. The EMPAG-HF study assessed the early start of empagliflozin 25 mg in hospitalized patients with ADHF and displayed improved diuresis and kidney function compared to standard therapy without compromising blood pressure (BP) [16]. The EMPULSE trial further reinforced inpatient use, showing that empagliflozin led to improvement of symptoms, physical limitations, and overall health status, as measured by the Kansas City Cardiomyopathy Questionnaire [17]. The EMPA-RESPONSE-AHF study exhibited reduced combined endpoints of worsening HF, rehospitalization, death within 60 days, and improved natriuretic peptide levels when patients were on empagliflozin [18]. Dapagliflozin similarly showed promise in this setting as it had favorable effects on symptom relief and decongestant in patients who were hospitalized with ADHF, regardless of ejection fraction or diabetes status [19].
These studies suggest that SGLT2i can be safely initiated and may be beneficial in the inpatient setting, including during episodes of ADHF. Importantly, across trials such as EMPAG-HF, EMPULSE, and EMPA-RESPONSE-AHF, there was no excess risk of hypotension, acute kidney injury, or other adverse events compared to placebo. Although endpoints like decongestion or diuresis were variably affected—such as in DELIVER, where natriuretic benefit was not significant—the safety profile supports initiation prior to discharge. This strategy ensures patients are started on guideline-directed medical therapy (GDMT) early in the disease course, avoiding the common practice of deferring initiation to outpatient follow-up, where opportunities may be missed.
Key Point: Clinical trials have demonstrated safety, and in some cases improved diuresis, in hospitalized patients with ADHF, suggesting the benefits of starting SGLT2i during a HF hospitalization.
Anzeige
Hypertension
SGLT2i provide significant clinical benefits beyond diabetes and HF management, including reduction of BP among those with HTN. Although clinical significance in comparison to first-line agents is yet to be determined, numerous clinical trials have demonstrated statistically significant reductions in BP with SGLT2i [20].
The EMPA REG-BP explored the effect of empagliflozin on BP in patients with T2DM and HTN. Daytime mean systolic and diastolic BP were significantly reduced from baseline using both 10 mg and 25 mg dosages of empagliflozin when compared to placebo [21]. Subsequent subgroup analysis of this cohort yielded data showcasing preservation of BP-reducing effects with lower renal function and similar BP reduction with concomitant use of other antihypertensive medications. Results from this trial suggested additional mechanisms of action of BP reduction by SGLT2i beyond glucosuria, such as osmotic diuresis, weight loss, and reduced arterial stiffness [22].
A post hoc analysis of the CREDENCE trial showcases additional benefits of canagliflozin on BP reduction in individuals with T2DM and CKD. A reduction in BP was noted among all participants, regardless of baseline average BP and concomitant antihypertensive use. Notably, initiation of canagliflozin reduced the need for additional BP-reducing agents [23]. Similarly, the DELIVER and DECLARE-TIMI 58 trials provide evidence of dapagliflozin having a significant effect on BP in those with T2DM and HF or atherosclerotic disease. Both trials presented data supporting dapagliflozin’s role in CV benefit [6, 14].
Overall, these major trials, in addition to numerous other studies and meta-analyses, provide evidence to conclude that SGLT2i may result in a modest reduction in systolic and diastolic BP readings regardless of baseline HTN status and concomitant antihypertensive use [20]. Additionally, the data from these studies support the known CV, renal, and glycemic benefits of SGLT2i. This evidence supports the potential inclusion of SGLT2i as adjuvant therapy in HTN management, but further studies are required to conclude on its overall clinical significance compared to first-line agents for BP control.
Key Point: Although the clinical significance has not been established, current evidence suggests that SGLT2i may result in a modest reduction in systolic and diastolic BP readings.
Atrial Fibrillation
AF has not been studied as a primary outcome in major CV trials of SGLT2i. Although emerging evidence suggests that SGLT2i may help reduce AF and related arrhythmia outcomes, dedicated research is needed to further determine the relationship between the two.
One retrospective cohort study of patients with T2DM undergoing AF ablation found that SGLT2i use was linked to a significantly lower risk of AF recurrence as measured by the need for cardioversion, new class I or III antiarrhythmic drugs, or repeat ablation [24].
Several systematic reviews and meta-analyses report that SGLT2i are associated with a reduced risk of AF (across occurrence, recurrence, and AF-related events), particularly in patients with T2DM or HF. Some analyses suggest the effect may be greater in subgroups such as patients with HFrEF, male individuals, those taking dapagliflozin, or those followed for longer periods [25‐28]. In a meta-analysis of patients with pre-existing AF, SGLT2i were associated with a reduced risk of HF hospitalizations. [29]. However, a separate meta-analysis of 46 randomized controlled trials found no significant effect on overall AF occurrence, even at a 1-year timepoint, highlighting inconsistencies in the evidence [30]. Importantly, this and other analyses were limited in that they utilized fixed-effects models. They also lacked individual patient-level data and highlighted inconsistencies in how AF events were recorded across included studies.
Together, these limitations highlight the need for prospective trials specifically designed to evaluate the impact of SGLT2i on AF-related outcomes.
Key Point: Although early evidence suggests that SGLT2i may one day play a role in the management of AF, more research is needed.
Chronic Kidney Disease
T2DM continues to be the leading cause of kidney disease, yet effective long-term pharmacological interventions to slow down CKD progression remain limited [31]. Early CV trials of SGLT2i suggest potential renal benefits, extending beyond glucose and CV control [32, 33]. The specific impact of SGLT2i on patients with CKD, regardless of the patient’s glycemic status, was solidified in large-scale clinical trials such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY [34‐36]. These trials demonstrated significant reductions in composite renal endpoints, including sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), and renal death [37]. Of note, these significant renal benefits were consistent among patients irrespective of their glycemic status.
Furthermore, the long-term effects of SGLT2i, specifically empagliflozin, in patients with CKD were evaluated in the post-trial follow-up sub-study of EMPA-KIDNEY to assess the extended benefits of empagliflozin after its discontinuation. The trial demonstrated that in a broad population of patients with CKD at risk for disease progression, empagliflozin sustained additional cardiorenal protection for up to 1 year after the medication was stopped [38].
Key Points: Large-scale clinical trials have shown that SGLT2i reduce rates of composite renal endpoints irrespective of glycemic status.
Guidelines
This section reviews guidelines of the American College of Cardiology/American Heart Association (ACC/AHA), European Society of Cardiology (ESC), and American Diabetes Association (ADA) pertaining to SGLT2i indications and use (Table 3).
Table 3
ACC/AHA, ESC, and ADA guidelines recommendations for SGLT2i use
Organization
Year
Guidelines
Class
Recommendation
ACC/AHA
2024
Perioperative CV management for NCS
I
In patients with HF undergoing elective NCS, SGLT2i should be withheld for 3–4 days before surgery when feasible to reduce the risk of perioperative metabolic acidosis
2024
Perioperative CV management for NCS
IIa
In patients with compensated HF undergoing elective NCS, SGLT2i should be withheld for 3–4 days before surgery when feasible to reduce the risk of perioperative metabolic acidosis
2024
Lower extremity PAD
I
In patients with PAD and T2DM, use of GLP-1 receptor agonist (liraglutide and semaglutide) and SGLT2i (canagliflozin, dapagliflozin, and empagliflozin) are effective to reduce the risk of MACE
2023
CCD
I
In patients with CCD who have T2DM, the use of either an SGLT2i or a GLP-1 receptor agonist with proven CV benefit is recommended to reduce the risk of MACE
2023
CCD
I
In patients with CCD and HF with LVEF ≤ 40%, use of an SGLT2i is recommended to reduce the risk of CVD and HF hospitalization and to improve QOL, irrespective of diabetes status
2022
HF
I
In patients with T2DM and either established CVD or at high CV risk, SGLT2i should be used to prevent hospitalizations for HF
2022
HF
I
In patients with symptomatic chronic HFrEF, SGLT2i are recommended to reduce hospitalization for HF and CV mortality, irrespective of the presence of T2DM
2022
HF
IIa
In patients with HFmrEF, SGLT2i can be beneficial in decreasing HF hospitalizations and CV mortality
2022
HF
IIa
In patients with HFpEF, SGLT2i can be beneficial in decreasing HF hospitalizations and CV mortality
2022
HF
III
In women with HF or cardiomyopathy who are pregnant or currently planning for pregnancy, ACEi, ARB, ARNi, MRA, SGLT2i, ivabradine, and vericiguat should not be administered because of significant risks of fetal harm
2019
Primary prevention
IIb
For adults with T2DM and additional ASCVD risk factors who require glucose-lowering therapy despite initial lifestyle modifications and metformin, it may be reasonable to initiate a SGLT2i or a GLP-1 receptor agonist to improve glycemic control and reduce CV risk
ESC
2024
HTN
Ia
In hypertensive patients with CKD and eGFR > 20 mL/min/1.73 m2, SGLT2i are recommended to improve outcomes in the context of their modest BP-lowering properties
2024
HTN
Ia
In hypertensive patients with symptomatic HFpEF, SGLT2i are recommended to improve outcomes in the context of their modest BP-lowering properties
2024
HTN
Ia
In patients with symptomatic HFrEF/HFmrEF, the following treatments with BP-lowering effects are recommended to improve outcomes: ACE inhibitors (or ARBs if ACE inhibitors are not tolerated) or ARNi, beta-blocker, MRA, and SGLT2i
2024
PAAD and CCS
Ia
SGLT2i with proven CV benefit are recommended in patients with T2DM and PAAD to reduce CV events, independent of baseline or target HbA1c and concomitant glucose-lowering medication
2024
AF
IIa B
Metformin or SGLT2i should be considered for individuals needing pharmacological management of diabetes mellitus to prevent AF
2024
CCS
Ia
An ACE-I, an MRA, an SGLT2i (dapagliflozin or empagliflozin), and, in stable conditions, a beta-blocker are recommended for patients with CCS and HFrEF to reduce the risk of HF hospitalization and death
2024
CCS
Ia
SGLT2i with proven CV benefit are recommended in patients with T2DM and CCS to reduce CV events, independent of baseline or target HbA1c and independent of concomitant glucose-lowering medication
2024
CCS
Ia
An SGLT2i (dapagliflozin or empagliflozin) is recommended in patients with HFmrEF or HFpEF to reduce the risk of HF hospitalization or CV death
2023
CVD and DM
Ia
SGLT2i (dapagliflozin, empagliflozin, or sotagliflozin) are recommended in all patients with HFrEF and T2DM to reduce the risk of HF hospitalization and CV death
2023
CVD and DM
Ia
An intensive strategy of early initiation of evidence-based treatment (SGLT2i, ARNI/ ACE-Is, beta-blockers, and MRAs), with rapid up-titration to trial-defined target doses starting before discharge and with frequent follow-up visits in the first 6 weeks following a HF hospitalization is recommended to reduce re-admissions or mortality
2023
CVD and DM
Ia
SGLT2i (canagliflozin, empagliflozin, or dapagliflozin) are recommended in patients with T2DM and CKD with an eGFR ≥ 20 mL/min/1.73 m2 to reduce the risk of CVD and kidney failure
2023
CVD and DM
Ia
SGLT2i with proven CV benefit are recommended in patients with T2DM and ASCVD to reduce CV events, independent of baseline or target HbA1c and independent of concomitant glucose-lowering medication
2023
CVD and DM
IIa C
In patients with T2DM without ASCVD or severe TOD but with a calculated 10-year CVD risk ≥ 10%, treatment with an SGLT2i or GLP-1 receptor agonist may be considered to reduce CV risk
2023
CVD and DM
Ia
SGLT2i (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, or sotagliflozinc) are recommended in patients with T2DM with multiple ASCVD risk factors or established ASCVD to reduce the risk of HF hospitalization
2023
CVD and DM
Ia
SGLT2i (dapagliflozin, empagliflozin, or sotagliflozinc) are recommended in patients with T2DM and HFrEF to reduce the risk of HF hospitalization and CV death
2023
HF
Ia
SGLT2i (dapagliflozin or empagliflozin) are recommended in patients with HFmrEF to reduce the risk of HF hospitalization or CV death
2023
HF
Ia
SGLT2i (dapagliflozin or empagliflozin) are recommended in patients with HFpEF to reduce the risk of HF hospitalization or CV death
2023
HF
Ia
In patients with T2DM and CKD, SGLT2i are recommended to reduce the risk of HF hospitalization or CV death
2022
Ventricular arrhythmias and prevention of SCD
Ia
Optimal medical treatment including ACE-I/ARB/ARNIs, MRAs, beta-blockers, and SGLT2i is indicated in all HF patients with reduced EF
ADA
2024
CV disease and risk management
A
In individuals with diabetes, GDMT for MI and symptomatic stage C HF is recommended with ACE inhibitors/ARBs, MRAs, ARNi, b-blockers, and SGLT2i, similar to GDMT for people without diabetes
2023
CV disease and risk management
A
In patients with T2DM and established HF with either HFpEF or HFrEF, an SGLT2i with proven benefit in this patient population is recommended to improve symptoms, physical limitations, and quality of life
2022
CV disease and risk management
A
In patients with T2DM and established HFpEF or HFrEF, an SGLT2i with proven benefit in this patient population is recommended to reduce risk of worsening HF, hospitalizations for HF, and CV death
2020
CV disease and risk management
A
In patients with T2DM and established ASCVD, multiple ASCVD risk factors, or DKD, an SGLT2i with demonstrated CV benefit is recommended to reduce the risk of MACE and HF hospitalization
ACC/AHA and ESC utilize a class of recommendation (1, 2a, 2b, 3) which highlights the overall benefit of a treatment compared to its risks. Class 1 = Recommendation is indicated/useful/effective/beneficial; Class 2a = Recommendation can be useful/effective/beneficial; Class 2b = Recommendations usefulness/effectiveness is unknown/unclear/uncertain or not well established; Class 3 = Recommendation is not indicated/useful/effective/beneficial; No class assigned = more evidence is needed to ascertain a recommendation. The ADA uses a grading system (A, B, C, E to show evidence level that supports each recommendation. Grade A = Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered; Grade B = Supportive evidence from well-conducted cohort studies; Grade C = Supportive evidence from poorly controlled or uncontrolled studies; Grade E = Expert consensus or clinical experience
ACC American College of Cardiology, AHA American Heart Association, ESC European Society of Cardiology, ADA American Diabetes Association, CV cardiovascular, NCS non-cardiac surgery, HF heart failure, SGLT2i sodium–glucose cotransporter 2 inhibitors, PAD peripheral arterial disease, T2DM type 2 diabetes mellitus, GLP-1 glucagon-like peptide 1, MACE major adverse cardiovascular events, CCD chronic coronary disease, LVEF left ventricular ejection fraction, QOL quality of life, CVD cardiovascular disease, HFrEF heart failure with reduced ejection fraction, HFmrEF heart failure with mildly reduced ejection fraction, HFpEF heart failure with preserved ejection fraction, ACEi angiotensin-converting enzyme inhibitors, ARB angiotensin receptor blockers, ARNi angiotensin receptor–neprilysin inhibitors, MRA mineralocorticoid receptor antagonists, ASCVD atherosclerotic cardiovascular disease, HTN hypertension, CKD chronic kidney disease, eGFR estimated glomerular filtration rate, BP blood pressure, PAAD peripheral arterial and aortic disease, CCS chronic coronary syndrome, AF atrial fibrillation, HbA1c hemoglobin A1c, DM diabetes mellitus, TOD target organ damage, MI myocardial infarction, DKD diabetic kidney disease
Recommendations listed in this table are sourced directly from their corresponding organizations’ published guidelines. Changes to the wording and abbreviations are minimal in order to accurately reflect the intended recommendation. The following resources were used: Thompson et al. [43]; Virani et al. [71]; Heidenreich et al. [72]; Arnett et al. [40]; Isselbacher et al. [41]; Joglar et al. [42]; McEvoy et al. [73]; Mazzolai et al. [74]; Van Gelder et al. [75]; Vrints et al. [76]; Marx et al. [46]; McDonagh et al. [45]; Al-Khatib et al. [77]; American Diabetes Association [49]; American Diabetes Association Professional Practice Committee [51]; ElSayed et al. [52]; American Diabetes Association Professional Practice Committee [53]
ACC Guidelines
The 2019 ACC/AHA guidelines for the management of T2DM and CV risk recommended the use of SGLT2i in adults with T2DM and additional atherosclerotic cardiovascular disease (ASCVD) risk factors who require glucose-lowering therapy despite initial lifestyle modifications and metformin. SGLT2i, along with glucagon-like peptide 1 (GLP-1) receptor agonists, were considered reasonable options to improve glycemic control and reduce CV risk, with a class IIb recommendation [40].
In 2022, the ACC/AHA further emphasized the role of SGLT2i in patients with HF. For those with HFpEF or HFmrEF, SGLT2i received a class IIa recommendation for reducing hospitalizations due to HF and improving CV outcomes. Notably, in symptomatic HFrEF, SGLT2i were given a class I recommendation, irrespective of the presence of T2DM, for reducing hospitalization and CV mortality [41].
The 2023 ACC/AHA guidelines on HF and chronic coronary disease (CCD) reinforced the benefits of SGLT2i. In patients with HF and a left ventricular ejection fraction (LVEF) ≤ 40%, SGLT2i were strongly recommended (class I) to reduce the risk of CV death, HF hospitalizations, and to improve quality of life. In patients with CCD and T2DM, either SGLT2i or GLP-1 receptor agonists were recommended (class I) to reduce the risk of MACE [42].
In 2024, the ACC/AHA guidelines further expanded the use of SGLT2i to patients with peripheral arterial disease (PAD) and T2DM. These patients received a class I recommendation for the use of SGLT2i, as they have demonstrated efficacy in reducing the risk of MACE. However, for patients undergoing elective non-cardiac surgery (NCS) with compensated HF or those with HF undergoing elective NCS, SGLT2i should be withheld for 3–4 days before surgery to reduce the risk of perioperative metabolic acidosis (class I) [43].
ESC Guidelines
The 2021 ESC Guidelines for the diagnosis and treatment of HF established SGLT2i as a foundational therapy for HFrEF, independent of diabetes status. Both dapagliflozin and empagliflozin received a class I, level A recommendation for all symptomatic patients with HFrEF to reduce hospitalization and mortality risk. This marked a major paradigm shift, incorporating SGLT2i into the standard therapy alongside beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors, or mineralocorticoid receptor antagonists [44].
The 2023 ESC Heart Failure Press Update expanded upon this guidance, highlighting dapagliflozin’s benefit in HF with HFmrEF and HFpEF based on the DELIVER trial. This was reflected in an updated class I recommendation for SGLT2i across the ejection fraction spectrum in symptomatic patients [45].
The 2023 ESC Guidelines on diabetes and CVD recommend SGLT2i as first-line agents in patients with T2DM at high CV risk, particularly for those with established ASCVD, HF, or CKD. These agents received a class I recommendation for reducing CV events and progression of cardiorenal disease. While not antihypertensives per se, SGLT2i are noted to have modest BP-lowering effects, but are not indicated for primary HTN management. No specific recommendation was made for AF prevention or rhythm management [46].
ADA Guidelines
The ADA has steadily broadened and strengthened its recommendations for SGLTi in its annual Standards of Medical Care in Diabetes. In 2018, empagliflozin received an A-level recommendation for reducing MACE and CV mortality in patients with T2DM and established ASCVD [47]. In 2019, this recommendation was expanded to include both empagliflozin and canagliflozin, and a new C-level recommendation highlighted SGLTi as preferred for patients with ASCVD who were at high risk for HF or had coexisting HF [48]. In 2020, dapagliflozin was added, further expanding the list of recommended agents [49].
In 2021, the ADA increased its recommendation to an A-level for using SGLTi in patients with T2DM and HFrEF to reduce the risk of worsening HF and CVD [50]. This was expanded in 2022 to include both HFrEF and HFpEF, with evidence supporting reductions in worsening HF, hospitalizations for HF, and CVD [51]. In 2023, the recommendation was further strengthened to include the additional benefits of SGLT2i in improving symptoms, physical limitations, and quality of life in patients with HFpEF and HFrEF [52].
In 2024, the guidelines integrated SGLT2i as part of GDMT for myocardial infarction (MI) and symptomatic stage C HF in people with diabetes, aligning them with therapies used for people without diabetes [53]. In 2025, the ADA reaffirmed SGLT2i as a cornerstone of CV and HF care for a broad range of patients with diabetes, with A-level evidence for reducing MACE, HF hospitalizations, CVD, and improving overall quality of life in those with ASCVD, HFrEF, and HFpEF [54].
Practical Aspects
Current guidelines suggest SGLT2i should be considered in patients with HF, CKD, and T2DM, with or without CVD or CV risk factors. The benefits of selecting these agents for their glucose-lowering effects should be weighed against the benefits of alternative diabetes medications. For example GLP-1 RAs may be more favorable in patients with higher ASCVD risk or obesity [11].
Table 4 outlines dosing regimens for SGLT2i available in the USA. All SGLT2i are taken orally once daily. Dose adjustment recommendations are different depending on the indication [55]. Additionally, they are currently not recommended for initiation in patients with severe CKD because of a lack of clinical data to support their benefits in patients with low eGFRs [56]. The ADA and KDIGO currently recommend SGLT2i for most patients with T2DM and CKD with eGFR ≥ 20 mL/min/1.73 m2. Once initiated, the SGLT2i can be continued even when eGFR drops below 20 mL/min/1.73 m2 [39].
Table 4
Dosing regimen for SGLT2i available in the USA
Medication
Starting dose
Target dose
Titration frequency
eGFR (mL/min/1.73 m2) cutoffs for initiation
Empagliflozin
10 mg daily
10 mg daily (HF)
25 mg daily (T2DM)
After 4–12 weeks
Do not initiate in eGFR < 25–30, regardless of indication
Canagliflozin
100 mg daily
Increase to 300 mg daily (T2DM, CAD)
After 4–12 weeks
Do not initiate in eGFR < 25–3,0 regardless of indication
Dapagliflozin
5 mg daily (T2DM)
10 mg daily (HF, HTN)
10 mg daily (T2DM)
After 4–12 weeks
Do not initiate in eGFR < 25 for HF and CKD
Do not initiate in eGFR < 45 for T2DM
Sotagliflozin
200 mg daily
400 mg daily
After 2 weeks
Do not initiate in eGFR < 25 regardless of indication
Side effects of SGLT2i include urinary tract infections, especially fungal, which may be associated with induced glucosuria [57]. Recurrent genitourinary infections can be a contraindication to SGLT2i use. A rare but severe adverse effect of SGLT2i is euglycemic diabetic ketoacidosis (euDKA). An interplay of elevated glucagon levels and increased ketogenesis are noted with use of SGLT2i [58]. As noted previously, guidelines suggest holding SGLT2i 3–4 days prior to major surgical intervention in order to reduce risk of euDKA in the postoperative period. If euDKA occurs while on an SGLT2i, the medication should be discontinued. Re-initiation of SLGT2i in this setting should be individualized depending on the reversible nature of the events leading to euDKA and the potential overall benefits of the medication. Lastly, controversy has surrounded the concerns of lower extremity amputations while on SGLT2i. While initial data from the US Food and Drug Administration (FDA)’s Adverse Event Reporting System showed an increased risk of lower extremity amputations in patients on canagliflozin, subsequent studies have shown that this risk is not clinically significant [59, 60].
It is important to note that upon initiation of therapy, a decline in eGFR up to 10% from baseline can be expected [61]. In patients on concomitant loop diuretics, it is imperative to pay close attention to volume status and signs of dehydration. While empiric reductions in loop diuretics are not recommended, SGLT2i may reduce loop diuretic requirements in patients with HF over time [62].
Ongoing Trials
While large randomized controlled trials have established the CV and renal benefits of SGLT2i, a number of studies are now exploring their role in acute care settings and novel patient populations, with several trials expected to report results in 2025 and beyond (Table 5). These trials underscore the expanding scope of SGLT2i therapy. One evolving area of interest is use of SGLT2i to reduce the risk of cancer-related cardiac dysfunction. Recent observational studies have demonstrated decreased rates of cardiac events, and even cardiac dysfunction in patients with diabetes receiving chemotherapy [63, 64]. Beyond cardiotoxicity, future studies are poised to expand what we know about use of SGLT2i in the setting of early intervention, arrhythmia prevention, post-ischemic remodeling, and cardiogenic shock [65‐70]. These findings are anticipated to shape future guideline recommendations and further broaden the clinical utility of SGLT2i in CV medicine.
Table 5
Ongoing trials for SGLT2i
Trial name
Drug
Population
EE
Type
Clinical question
Primary end-points
EC
Country
EMPA-CON
Empagliflozin
ADHF
556
RCT
Is continuation of empagliflozin during HF hospitalization superior to temporary cessation?
All-cause mortality
HF rehospitalization
Renal function decline
2026
Germany, Brazil
EMPA-SHOCK
Empagliflozin
Cardiogenic shock
164
RCT
Does initiation of empagliflozin in patients recovering from cardiogenic shock improve outcomes?
All-cause mortality
Time to heart transplant
Time to MVA
HF rehospitalization
LVEF
Myocardial function at 12 weeks
2027
France
EMPOAF
Empagliflozin
CABG candidates
492
RCT
Can initiation of empagliflozin prevent postoperative AF?
New-onset postoperative AF and/or AFL
2025
Iran
DAPA-MEMRI
Dapagliflozin
HF, T2DM
160
RCT
Does dapagliflozin improve calcium handling (via MEMRI) in patients with HF?
Rate of change in myocardial T1 values with manganese-enhanced cardiac MR
2028
UK
PROTECT
Dapagliflozin
Breast cancer
316
RCT
Does dapagliflozin reduce chemotherapy-induced cardiotoxicity in participants with breast cancer?
Asymptomatic and symptomatic CTRCD
Change of LVEF
Change of GLS
2025
Italy
RECORD-AMI
Not specified
AMI, T2DM
1000
RCT
Does use of SGLT2i reduce CV events and modify LV remodeling after MI?
Composite of cardiac death, nonfatal MI, nonfatal stroke, and HF hospitalization
2026
South Korea
EE estimated enrollment, EC stimated completion, ADHF acute decompensated heart failure, RCT randomized control trial, HF heart failure, MVA mechanical ventricular assist, LVEF left ventricular ejection fraction, CABG coronary artery bypass graft, AF atrial fibrillation, AFL atrial flutter, T2DM type 2 diabetes mellitus, MEMRI manganese-enhanced magnetic resonance imaging, MR magnetic resonance, CTRCD cancer therapy-related cardiac dysfunction, GLS global longitudinal strain, AMI acute myocardial infarction, SGLT2i sodium–glucose cotransporter 2 inhibitors, CV cardiovascular, LV left ventricle, MI myocardial infarction
Conclusion
SGLT2i have rapidly evolved into foundational therapies in CV medicine, with benefits that extend well beyond glucose lowering. Large outcome trials have consistently shown that these agents reduce HF hospitalizations and CV mortality across a broad spectrum of patients—including those with HFrEF, HFpEF, and CKD. As with any therapy, careful patient selection—factoring in eGFR, volume status, and risk of genitourinary side effects—is essential, and periodic monitoring is recommended. Looking ahead, trials focused on early intervention, arrhythmia prevention, post-ischemic remodeling, cardiogenic shock, and cardioprotection in high-risk groups will further delineate the therapeutic horizon of SGLT2i and guide the next wave of CV care.
Declarations
Conflict of Interest
Zaid Zayyad, Neil Gupta, Aanya Roy, Swetha Kalagara, Atreya Mishra, Edward Salem, Suhas Rathna Seshadri, Deema Gichi, Bayan A Hammad, Adriana Ene, Kayla Torres, Stephanie Dwyer Kalzuna, and Adhir R Shroff declare that they have no competing interests.
Ethical Approval
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Hitting the Sweet Spot: A Review of SGLT2i in Cardiovascular Medicine
Verfasst von
Zaid A. Zayyad
Neil Gupta
Aanya Roy
Swetha Kalagara
Atreya Mishra
Edward Salem
Suhas Rathna Seshadri
Deema Gichi
Bayan A. Hammad
Adriana Ene
Kayla Torres
Stephanie Dwyer Kalzuna
Adhir R. Shroff
Karg MV, Bosch A, Kannenkeril D, et al. SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial. Cardiovasc Diabetol. 2018;17(1):5.PubMedPubMedCentralCrossRef
2.
Vasilenko T, Charytan DM, Wanner C, et al. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(4):484–95. https://doi.org/10.1016/j.jacc.2019.11.031.CrossRef
3.
Verma S, McMurray JJ. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61(10):2108–17.PubMedCrossRef
4.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.PubMedCrossRef
5.
Neal B, Perkovic B, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. New Engl J Med. 2017;377(7):644–57.PubMedCrossRef
6.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–57.PubMedCrossRef
7.
Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. New Engl J Med. 2020;383:1425–35.PubMedCrossRef
8.
Paolisso P, Bergamaschi L, Gragnano F, et al. Outcomes in diabetic patients treated with SGLT2-inhibitors with acute myocardial infarction undergoing PCI: the SGLT2-I AMI protect registry. Pharmacol Res. 2023;187:106597.PubMedCrossRef
9.
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008.PubMedCrossRef
10.
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61.PubMedCrossRef
11.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306.PubMedCrossRef
12.
Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384(2):129–39.PubMedCrossRef
13.
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–24.PubMedCrossRef
14.
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089–98.PubMedCrossRef
15.
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117–28.PubMedCrossRef
16.
Schulze PC, Bogoviku J, Westphal J, et al. Effects of early empagliflozin initiation on diuresis and kidney function in patients with acute decompensated heart failure (EMPAG-HF). Circulation. 2022;146(4):289–98.PubMedCrossRef
17.
Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568–74.PubMedPubMedCentralCrossRef
18.
Damman K, Beusekamp JC, Boorsma EM, et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur J Heart Fail. 2020;22(4):713–22.PubMedCrossRef
19.
Cox ZL, Collins SP, Hernandez GA, et al. Efficacy and safety of dapagliflozin in patients with acute heart failure. J Am Coll Cardiol. 2024;83(14):1295–306.PubMedCrossRef
20.
Gupta R, Maitz T, Egeler D, et al. SGLT2 inhibitors in hypertension: role beyond diabetes and heart failure. Trends Cardiovasc Med. 2023;33(8):479–86.PubMedCrossRef
21.
Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38(3):420–8.PubMedCrossRef
22.
Mancia G, Cannon CP, Tikkanen I, et al. Impact of empagliflozin on blood pressure in patients with type 2 diabetes mellitus and hypertension by background antihypertensive medication. Hypertension. 2016;68(6):1355–64.PubMedCrossRef
23.
Ye N, Jardine MJ, Oshima M, et al. Blood pressure effects of canagliflozin and clinical outcomes in type 2 diabetes and chronic kidney disease: insights from the CREDENCE trial. Circulation. 2021;143(18):1735–49.PubMedCrossRef
24.
Abu-Qaoud MR, Kumar A, Tarun T, et al. Impact of SGLT2 inhibitors on AF recurrence after catheter ablation in patients with type 2 diabetes. JACC Clin Electrophysiol. 2023;9(10):2109–18.PubMedCrossRef
25.
Fernandes GC, Fernandes A, Cardoso R, et al. Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: a meta-analysis of 34 randomized controlled trials. Heart Rhythm. 2021;18(7):1098–105.PubMedCrossRef
26.
Liao J, Ebrahimi R, Ling Z, et al. Effect of SGLT-2 inhibitors on arrhythmia events: Insight from an updated secondary analysis of > 80,000 patients (the SGLT2i—arrhythmias and sudden cardiac death). Cardiovasc Diabetol. 2024;23(1):8.CrossRef
27.
Pandey AK, Okaj I, Kaur H, et al. Sodium-glucose co-transporter inhibitors and atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2021;10(17):e022222.PubMedPubMedCentralCrossRef
28.
Zheng RJ, Wang Y, Tang JN, Duan JY, Yuan MY, Zhang JY. Association of SGLT2 inhibitors with risk of atrial fibrillation and stroke in patients with and without type 2 diabetes: a systemic review and meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol. 2022;79(2):e145–52.PubMedCrossRef
29.
Zheng S, Lai Y, Jiang C, et al. Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. Pacing Clin Electrophysiol. 2024;47(1):58–65.PubMedCrossRef
30.
Zhang HD, Ding L, Mi LJ, et al. Sodium-glucose co-transporter-2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis. Eur J Prev Cardiol. 2024;31(7):770–9.PubMedCrossRef
31.
Di Costanzo A, Esposito G, Indolfi C, Spaccarotella CAM. SGLT2 inhibitors: a new therapeutical strategy to improve clinical outcomes in patients with chronic kidney diseases. Int J Mol Sci. 2023;24(10):8732.PubMedPubMedCentralCrossRef
32.
Del Vecchio L, Beretta A, Jovane C, Peiti S, Genovesi S. A role for SGLT-2 inhibitors in treating non-diabetic chronic kidney disease. Drugs. 2021;81(13):1491–511.PubMedCrossRef
33.
Sarafidis P, Pella E, Kanbay M, Papagianni A. SGLT-2 inhibitors and nephroprotection in patients with diabetic and non-diabetic chronic kidney disease. Curr Med Chem. 2023;30(18):2039–60.PubMedCrossRef
34.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306.PubMedCrossRef
35.
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46.PubMedCrossRef
36.
The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117–27.CrossRef
37.
Sarafidis P, Ortiz A, Ferro CJ, et al. Sodium–glucose co-transporter-2 inhibitors for patients with diabetic and nondiabetic chronic kidney disease: a new era has already begun. J Hypertens. 2021;39(6):1090–7.PubMedCrossRef
38.
An Y, Zhang H. SGLT-2 inhibitors: a deeper dive into their renal protective properties beyond glycemic control and proteinuria reduction. Am J Nephrol. 2025;18:1–13.CrossRef
39.
de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022;45(12):3075–90.PubMedPubMedCentralCrossRef
40.
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74(10):e177–232. https://doi.org/10.1016/j.jacc.2019.03.010. (Erratum in: J Am Coll Cardiol. 2019 Sep 10;74(10):1429-1430).CrossRefPubMedPubMedCentral
41.
Isselbacher EM, Preventza O, Hamilton Black J 3rd, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;80(24):e223–393.PubMedCrossRef
42.
Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;83(1):109–279.PubMedCrossRef
43.
Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;84(19):1869–969.PubMedCrossRef
44.
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–726.PubMedCrossRef
45.
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2024;26(1):5–17.PubMedCrossRef
46.
Marx N, Federici M, Schütt K, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44(39):4043–140.PubMedCrossRef
47.
American Diabetes Association. Standards of medical care in diabetes-2018 abridged for primary care providers. Clin Diabetes. 2018;36(1):14–37.PubMedCentralCrossRef
48.
American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Suppl 1):S103–23.CrossRef
49.
American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2020. Diabetes Care. 2020;43(Suppl 1):S111–34.CrossRef
50.
American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S125–50.CrossRef
51.
American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(Suppl 1):S144–74.CrossRef
52.
ElSayed NA, Aleppo G, Aroda VR, et al. 10. Cardiovascular disease and risk management: standards of care in diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S158–90.PubMedCrossRef
53.
American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of care in diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S179–218.CrossRef
54.
American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of care in diabetes—2025. Diabetes Care. 2025;48(1 Suppl 1):S207–38.CrossRef
55.
Maddox TM, Januzzi JL Jr, Allen LA, et al. 2024 ACC Expert Consensus decision pathway for treatment of heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2024;83(15):1444–88.PubMedCrossRef
56.
Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations. Kidney Int Rep. 2022;7(7):1463–76.PubMedPubMedCentralCrossRef
57.
Li D, Wang T, Shen S, Fang Z, Dong Y, Tang H. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017;19(3):348–55.PubMedCrossRef
58.
Chow E, Clement S, Garg R. Euglycemic diabetic ketoacidosis in the era of SGLT-2 inhibitors. BMJ Open Diabetes Res Care. 2023;11(5):e003666.PubMedPubMedCentralCrossRef
59.
Fadini GP, Avogaro A. SGLT2 inhibitors and amputations in the US FDA Adverse Event Reporting System. Lancet Diabetes Endocrinol. 2017;5(9):680–1.PubMedCrossRef
60.
Heyward J, Mansour O, Olson L, Singh S, Alexander GC. Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: a systematic review and meta-analysis. PLoS ONE. 2020;15(6):e0234065.PubMedPubMedCentralCrossRef
61.
Umanath K, Testani JM, Lewis JB. “Dip” in eGFR: stay the course with SGLT-2 inhibition. Circulation. 2022;146(6):463–5.PubMedCrossRef
62.
Vardeny O. SGLT2 inhibitors and diuresis: a small piece of the puzzle. JACC Heart Fail. 2024;12(1):47–9.PubMedCrossRef
63.
Bhatti AW, Patel R, Dani SS, et al. SGLT2i and primary prevention of cancer therapy-related cardiac dysfunction in patients with diabetes. JACC CardioOncol. 2024;6(6):863–75.PubMedPubMedCentralCrossRef
64.
Dabour MS, George MY, Daniel MR, Blaes AH, Zordoky BN. The cardioprotective and anticancer effects of SGLT2 inhibitors: JACC CardioOncol state-of-the-art review. JACC Cardiooncol. 2024;6(2):159–82.PubMedPubMedCentralCrossRef
65.
Schulze C. Effects of continued administration of empagliflozin in patients with heart failure on active SGLT2 inhibitor treatment admitted for acute decompensated heart failure. clinicaltrials.gov. 2025. Report no. NCT07038356. https://clinicaltrials.gov/study/NCT07038356. Accessed 2025 July 27.
66.
Central Hospital, Nancy, France. Effect at 3 months of early empagliflozin initiation in cardiogenic shock patients on mortality, rehospitalization, left ventricular ejection fraction and renal function. clinicaltrials.gov. 2025. Report no. NCT05879276. https://clinicaltrials.gov/study/NCT05879276. Accessed 2025 July 27.
67.
Rajaie Cardiovascular Medical and Research Center. Empagliflozin to prevent post-operative atrial fibrillation. clinicaltrials.gov. 2023. Report no. NCT06124937. https://clinicaltrials.gov/study/NCT06124937. Accessed 2025 July 27.
Fondazione IRCCS Policlinico San Matteo di Pavia. Potential protective role of SGLT-2 inhibitors for chemotherapy-induced cardiotoxicity. clinicaltrials.gov. 2024. Report no. NCT06341842. https://clinicaltrials.gov/study/NCT06341842. Accessed 2025 July 27.
70.
Chang K. SGLT2 inhibitors on clinical outcomes and left ventricular remodeling in type 2 diabetic patients with acute myocardial infarction, a prospective, multi-center registry study. clinicaltrials.gov. 2025. Report no. NCT05770687. https://clinicaltrials.gov/study/NCT05770687. Accessed 2025 July 27.
71.
Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2023;82(9):833–955. https://doi.org/10.1016/j.jacc.2023.04.003.CrossRefPubMed
72.
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263–421. https://doi.org/10.1016/j.jacc.2021.12.012.CrossRefPubMed
73.
McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC guidelines for the management of elevated blood pressure and hypertension: developed by the Task Force of the European Society of Cardiology (ESC); endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). Eur Heart J. 2024;45(38):3912–4018. https://doi.org/10.1093/eurheartj/ehae178.CrossRefPubMed
Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC guidelines for the management of atrial fibrillation: developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314–414. https://doi.org/10.1093/eurheartj/ehae176.CrossRefPubMed
Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;43(40):3997–4126.CrossRef
Im Fall einer periprothetischen Gelenkinfektion kann die antibiotische Behandlung wohl frühzeitig von intravenös auf oral umgestellt werden, ohne dass der Therapieerfolg darunter leidet. Das zeigen die Ergebnisse einer neuen Metaanalyse.
Mangels verfügbarem HPV-Impfstoffs sind derzeit nur 27% der Mädchen weltweit geimpft. Um die Durchimpfung zu beschleunigen, hat die WHO ihre Empfehlungen auf eine Dosis angepasst. Nun zeigt eine große Studie, ob eine einzelne Impfdosis tatsächlich so wirksam wie zwei ist.
Steckt hinter den gehäuft auftretenden Infekten ein primärer Immundefekt? Eine neue S3-Leitlinie soll bei dieser Frage weiterhelfen. Hinter den Akronymen „ELVIS“ und „GARFIELD“ verbergen sich diagnostische Kriterien, von Markerpathogenen bis zu typischen Manifestationen.
Ein Patient entwickelt unter Gabapentin ein Beinödem – und bekommt deshalb ein Schleifendiuretikum verschrieben. Welche Folgen diese offenbar häufig anzutreffende Verschreibungskaskade haben kann, gerade bei Senioren, legt ein US-Team dar. Das Studiendesign gibt allerdings Anlass zur Kritik.
