Safety Of Dapagliflozin Research Articles

Effects of Dapagliflozin in Asian Patients With HeartFailure and Reduced Ejection Fraction in DAPA-HF.

Patients with heart failure with reduced ejection fraction (HFrEF) in Asia exhibit many differences from those in other parts of the world. This study sought to investigate the efficacy and safety of dapagliflozin, compared with placebo, in HFrEF patients in Asia, compared with those elsewhere, enrolled in the DAPA-HF (Dapagliflozin and Prevention of Adverse-outcomes in HeartFailure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for the DAPA-HF trial. The primary outcome in the DAPA-HF trial was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4,744 patients in the DAPA-HF trial, 1,096 (23.1%) were enrolled in Asia; 721 (15.2% overall, 65.8% of patients in Asia) were enrolled in East Asia (237 in China, 343 in Japan, and 141 in Taiwan), 138 (2.9% overall, 12.6% in Asia) in South-East Asia (Vietnam), and 237 (5.0% overall, 21.6% in Asia) in South Asia (India). Patients from Asia had similar rates of worsening HF events and mortality compared with patients elsewhere. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients from Asia (HR: 0.65; 95%CI: 0.49 to 0.87) as elsewhere (HR: 0.77; 95%CI: 0.66 to 0.89) (P for interaction=0.32). Consistent benefits were observed for the other prespecified outcomes and among the regions of Asia. Study drug discontinuation and prespecified adverse events did not differ between regions. Dapagliflozin, compared with placebo, reduced the risk of worsening HF events and cardiovascular death to the same extent in Asian patients as elsewhere. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening HeartFailure or Cardiovascular Death in Patients With Chronic HeartFailure [DAPA-HF]; NCT03036124).

The clinical efficacy and safety of dapagliflozin in patients with diabetic nephropathy

ObjectiveTo investigate the clinical efficacy and safety of dapagliflozin in the treatment of diabetic nephropathy (DN).MethodsA total of 120 DN patients admitted to our hospital from June 2017 to March 2020 were divided into control and experimental groups, with 60 cases in each group. The control group received valsartan, and the experimental group received dapagliflozin for 3 months. Body mass index (BMI), hemoglobin A1c (HbA1c), serum creatinine (sCr), uric acid (UA), urine microalbumin (uMA), urine creatinine (uCr), and bilateral kidney function were compared before and after treatment, and adverse reactions in both groups were observed. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were also evaluated.ResultsAfter treatment, except for BMI in the control group, all indexes in both groups were significantly improved. The BMI, HbA1c, sCr, UA, and uMA/uCr ratios of the experimental group were lower than those of the control group. Serum albumin (sAlb) levels were increased in both groups, and the experimental group showed a significant difference compared with the control group. Estimated glomerular filtration rate (eGFR) levels were increased in both groups, and the experimental group was higher than the control group, with no significant differences. Serum IL-6 and TNF-α levels in both groups were lower, and the experimental group was significantly lower than the control group. No serious adverse reactions were observed in either group.ConclusionThe efficacy of dapagliflozin was demonstrated by its ability to improve diabetes, prevent nephropathy exacerbation, and reduce symptomatic reactions. The low rate of adverse reactions makes dapagliflozin a very safe medication.

Dapagliflozin for nonalcoholic fatty liver disease: A systematic review and meta-analysis

ObjectivesA few randomized controlled trials (RCTs) have assessed the use of dapagliflozin for the treatment of nonalcoholic fatty liver disease (NAFLD). A systematic review and meta-analysis was performed to investigate the efficacy and safety of dapagliflozin in adults with NAFLD. Methods: We performed a comprehensive literature search of PubMed, Embase, Cochrane Library, CNKI and ClinicalTrials.gov for RCTs that assessed the use of dapagliflozin in patients with NAFLD. Risk ratios and mean differences with 95% confidence intervals were used to synthesize the results. Two authors independently extracted the data, evaluated the study quality and calculated pooled estimates. Results: Eleven studies involving 839 patients were included. Compared with the control conditions, dapagliflozin led to a greater decrease in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, triglyceride, body weight, body mass index, HbA1c, and fasting plasma glucose. No difference was found between the dapagliflozin and control groups in terms of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrosis 4 index, type IV collagen 7S, homeostatic model assessment of insulin resistance, or adverse events. Conclusions: Dapagliflozin can markedly reduce hepatic enzymes and metabolic indicators and improve body composition, indicating its potential therapeutic efficacy.

Effectiveness and safety of dapagliflozin in real-life patients: data from the DAPA-RWE Spanish multicentre study.

BackgroundThis study aims to evaluate dapagliflozin in patients with type 2 diabetes (T2D) in clinical practice in Spain.MethodsThis is a retrospective study including adults with T2D under stable antidiabetic therapy, with either dapagliflozin or sitagliptin ≥6 months, before inclusion. Data about the effectiveness and safety of dapagliflozin are presented.ResultsA total of 594 patients (61.8±9.9 years, 21.7% cardiovascular disease) were included. After 6 months, HbA1c, weight, blood pressure, urine albumin-to-creatinine ratio and uric acid significantly decreased (1.63%, 2.88 kg, 4.82/2.70 mmHg, −17.38 mg/g and −0.30 mg/dL, respectively), whereas glomerular filtration rate and haematocrit significantly increased (3.72 mL/min/1.73 m2 and 1.8%, respectively). No cases of hypoglycaemia, diabetic ketoacidosis, Fournier gangrene, fractures or amputations were reported.ConclusionThus, dapagliflozin provides a comprehensive cardiometabolic protection in patients with T2D.

Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions

IntroductionThis study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region.MethodsAdults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America.ResultsThe relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48–1.00), 0.60 (0.43–0.85), 0.61 (0.43–0.86), and 0.51 (0.34–0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively).ConclusionDapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.

POS-202 DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE TREATED WITH MINERALOCORTICOID RECEPTOR ANTAGONISTS: PRE-SPECIFIED ANALYSIS OF THE DAPA-CKD TRIAL

Both mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed a prespecified analysis of the DAPA-CKD trial to assess the efficacy and safety of dapagliflozin by baseline prescription of MRAs.

THE CLINICAL EXPERIENCE OF THE EFFECTIVE USE OF DAPAGLIFLOZIN IN COMORBID CARDIAC PATIENTS WITH CONCOMITANT TYPE 2 DIABETES MELLITUS AND ARTERIAL HYPERTENSION ON THE BACKGROUND OF OVERWEIGHT IN OUTPATIENT SETTING.

The aim: To assess the efficacy and safety of dapagliflozin in the treatment of comorbid cardiac patients with type 2 diabetes mellitus (T2DM) in combination with arterial hypertension (AH) and overweight in outpatient setting. Materials and methods: Under observation were 19 patients who were treated in outpatient setting during 2019-2021 for AH and had T2DM, overweight or obesity. As part of complex treatment, patients received dapagliflozin 10 mg once a day for 12 months. Results: The normalization of blood pressure, elimination of heart failure symptoms on the background of increased ejection fraction, improved indicators of the functional capacity of the kidneys, and a decrease in the degree of proteinuria/albuminuria were noted after treatment. The patients had an easier time losing weight (body mass index and waist circumference decreased; p<0.05) and decreased levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). None of the monitored patients had cases of hypoglycemia or urinary tract infection. The number and/or doses of antihypertensive, hypouricemic and diuretic drugs were gradually reduced. Conclusions: Using dapagliflozin in a standard dose of 10 mg/day in the complex therapy of patients with T2DM in combination with arterial hypertension and overweight contributes not only to the normalization of blood pressure, but also to a reduction in body weight and waist circumference. The proposed therapy can be an alternative for the treatment of patients with T2DM with concomitant overweight or obesity, arterial hypertension, with or without heart and/or renal failure as a first-line antidiabetic drug.

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial

ABSTRACTBackgroundDespite renin–angiotensin–aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy.MethodsIn DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200–5000 mg/g (22.6–565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment).ResultsOf 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749–2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (−4.5, 95% CI −5.9 to −3.1 versus −0.9, −2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were −1.9 (−3.0, −0.9) and −4.0 (−4.9, −3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin.ConclusionsAmong DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.

Dapagliflozin and atrial fibrillation in heart failure with reduced ejection fraction: insights from DAPA-HF.

Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62-0.92 and 0.74, 95% CI 0.62-0.88, respectively; p for interaction=0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60-1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF.

Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide: Insights From the DAPA-HF Trial.

Effective therapies for HFrEF usually reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP. We evaluated both these questions in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and a NT-proBNP level ≥600 pg/mL (≥600 ng/L; ≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter) were eligible. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Of the 4744 randomized patients, 4742 had an available baseline NT-proBNP measurement (median, 1437 pg/mL [interquartile range, 857-2650 pg/mL]). Compared with placebo, treatment with dapagliflozin significantly reduced NT-proBNP from baseline to 8 months (absolute least-squares mean reduction, -303 pg/mL [95% CI, -457 to -150 pg/mL]; geometric mean ratio, 0.92 [95% CI, 0.88-0.96]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of baseline NT-proBNP quartile; the hazard ratio for dapagliflozin versus placebo, from lowest to highest quartile was 0.43 (95% CI, 0.27-0.67), 0.77 (0.56-1.04), 0.78 (0.60-1.01), and 0.78 (0.64-0.95); P for interaction=0.09. Consistent benefits were observed for all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement (≥5 points) in Kansas City Cardiomyopathy Questionnaire total symptom score (P for interaction=0.99) and decreased the proportion with a deterioration ≥5 points (P for interaction=0.87) across baseline NT-proBNP quartiles. In patients with HFrEF, dapagliflozin reduced NT-proBNP by 300 pg/mL after 8 months of treatment compared with placebo. In addition, dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, across the spectrum of baseline NT-proBNP levels included in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Efficacy of Dapagliflozin in Black Versus White Patients With Heart Failure and Reduced Ejection Fraction

ObjectivesThis study sought to investigate the efficacy and safety of dapagliflozin in Black and White patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure). BackgroundBlack patients may respond differently to certain treatments for HFrEF than White patients. MethodsPatients with New York Heart Association functional class II to IV with an ejection fraction of ≤40% and elevated N-terminal pro–B-type natriuretic peptide were eligible for DAPA-HF. Because >99% of Black patients were randomized in the Americas, this post hoc analysis considered Black and White patients enrolled only in North and South America. The primary outcome was the composite of a worsening HF event (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. ResultsOf the 4,744 patients randomized in DAPA-HF, 1,494 (31.5%) were enrolled in the Americas. Of these, 1,181 (79.0%) were White, and 225 (15.1%) were Black. Black patients had a higher rate of worsening HF events, but not mortality, compared with White patients. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint similarly in Black patients (HR: 0.62; 95% CI: 0.37-1.03) and White patients (HR: 0.68; 95% CI: 0.52-0.90; P-interaction = 0.70). Consistent benefits were observed for other prespecified outcomes, including the composite of total (first and repeat) HF hospitalizations and cardiovascular death (P-interaction = 0.43) and Kansas City Cardiomyopathy Questionnaire total symptom score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either Black or White patients. ConclusionsDapagliflozin reduced the risk of worsening HF and cardiovascular death, and it improved symptoms, similarly in Black and White patients without an increase in adverse events. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124)

Rationale and design of the Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) randomized trial.

Despite aortic stenosis (AS) relief, patients undergoing transcatheter aortic valve implantation (TAVI) are at increased risk of developing heart failure (HF) within first months of intervention. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have been shown to reduce the risk of HF hospitalization in individuals with diabetes mellitus, reduced left ventricular ejection fraction and chronic kidney disease. However, the effect of SGLT-2 inhibitors on outcomes after TAVI is unknown. The Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) trial is designed to assess the clinical benefit and safety of the SGLT-2 inhibitor dapagliflozin in patients undergoing TAVI. DapaTAVI is an independent pragmatic, controlled, prospective, randomized, open-label blinded endpoint, multicentre trial conducted in Spain, evaluating the effect of dapagliflozin 10mg/day on the risk of death and worsening HF in patients with severe AS undergoing TAVI. Candidate patients should have prior history of HF admission plus ≥1 of the following criteria: (i) diabetes mellitus, (ii) left ventricular ejection fraction ≤40%, or (iii) estimated glomerular filtration rate between 25 and 75 ml/min/1.73 m2 . A total of 1020 patients will be randomized (1:1) to dapagliflozin vs. no dapagliflozin. Key secondary outcomes include: (i) incidence rate of individual components of the primary outcome; (ii) cardiovascular mortality; (iii) the composite of HF hospitalization or cardiovascular death; and (iv) total number of HF rehospitalizations. DapaTAVI will determine the efficacy and safety of dapagliflozin in a broad spectrum of frail patients after AS relief by TAVI.

Influence of cardiovascular drugs on the efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial

Abstract Background In DECLARE-TIMI 58, the sodium glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in a broad range of patients with type 2 diabetes mellitus (T2DM). SGLT2i are known to have diuretic and anti-hypertensive effects. However, whether concomitant CV drugs influence the efficacy and safety of dapagliflozin in these populations is less well known. Purpose We examined whether dapagliflozin consistently reduced the risk of CV outcomes and whether the safety of dapagliflozin was similar with or without the concurrent use of various CV drugs. Methods DECLARE–TIMI 58 was a randomized trial of dapagliflozin versus placebo in patients with T2DM and either atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for CV disease followed for a median of 4.2 years. We stratified patients by the use of CV drugs at baseline commonly used for heart failure: angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers (ACEi/ARB), beta-blockers, diuretics, and mineralocorticoid receptor antagonists (MRA). Efficacy outcomes of interest were the composite of CV death/HHF and HHF alone. We used the Cox proportional-hazard model for these analyses. Results Of 17,160 patients, 13,950 (81%) used ACEi/ARB, 9,030 (53%) used beta-blockers, 6,967 (41%) used diuretics, and 762 (4%) used MRA at baseline. All were balanced by randomized treatment groups. Patients using CV drugs at baseline had a greater prevalence of atherosclerotic risk factors and established CV disease than those without. Dapagliflozin consistently reduced the risk of CV death/HHF regardless of the use of CV medications (Figure). For HHF alone, similar results were seen with no significant interactions for any of the classes. There were no significant treatment interactions by the concomitant use of any of CV drugs for adverse events including symptoms of volume depletion or acute kidney injury. Conclusions In this analysis from the DECLARE–TIMI 58 trial, dapagliflozin consistently reduced the risk of CV death/HHF and HHF alone irrespective of the concurrent use of various CV drugs without any treatment interaction for key safety events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The DECLARE–TIMI 58 trial was supported by AstraZeneca.

The ADDition of DAPAgliflozin to angiotensin receptor blocker-neprilysin inhibitors non-responders in patient with refractory HFrEF

Abstract Objectives We evaluated the efficacy and safety of dapagliflozin, a SGLT2i along with ARNI in refractory HFrEF irrespective of their diabetic status. Methods We performed a prospective, open-label study of symptomatic patients of HFrEF despite of optimal medical management with ARNI between January–June 2020. Despite the maximum tolerated dose of ARNI and other medications in patients the symptoms of heart failure persisted. The initial dose of 5 mg was started and after 4 weeks irrespective of their glycemic control, then the dose was escalated to 10 mg. They were followed for the 6-months after the combination of ARNI and SGLT2i. Results The 104 patients who had HFrEF despite of optical medical management were added dapagliflozin on top of ARNI. The primary endpoint of mean change in Left Ventricular ejection fraction (LVEF) +9.00±0.62 with a significant p value of &amp;lt;0.001. The Mean difference in NYHA class was −2.9±0.057. A study of 104 patients at 6-months follow-up found that 92.6% of patients were in NYHA class I and 7.4% were in NYHA class II. They also reached the HbA1C goal of &amp;lt;7% in the diabetic subgroup. None of them had either symptomatic hypotension, dyselectrolytemia, and elevation of serum creatinine. The drug was well received by most patients (Picture 1). Conclusions Dapagliflozin are not only oral hypoglycaemic agents but can be used in refractory HFrEF despite the use of ARNI. The combination of the ARNI and SGLT2i is well tolerated but we need large, randomized trials to prove this hypothesis (Picture 2). Funding Acknowledgement Type of funding sources: None. Picture 1. Screening and outcomes of patientsPicture 2. Graphical abstract

ADDition of DAPAgliflozin, Sodium-Glucose Cotransporter-2 Inhibitor to Angiotensin Receptor Blocker-Neprilysin Inhibitors Non-Responders in Patient with Refractory Heart Failure with Reduced Ejection Fraction (ADD DAPA trial)

ObjectivesWe evaluated the efficacy and safety of dapagliflozin, a SGLT2i along with ARNI in refractory HFrEF irrespective of their diabetic status. MethodsWe performed a retrospective analysis of 104 symptomatic patients of HFrEF despite of optimal medical management with ARNI between January–June 2020. Despite the optimal GDMT, dapagliflozin, SGLT2i was added inpatients withrefractory heart failure. At 6-months follow-up, the primary outcome was change in left ventricular ejection fraction, and secondary outcomes included changes in NYHA functional class, vital parameters, renal function, potassium levels, and NT-pro BNP levels. ResultsThe primary outcomeat 6-months follow-up was a mean change in left ventricular ejection fraction (LVEF) +9.00 ± 0.62 (p < 0.001). The secondary outcome was a significant improvement (69%) in median NYHA functional class by 2.3 (95% Confidence interval 2.245–2.355) with 92.6% of patients were in NYHA class I and 7.4% were in NYHA class II.Diabetic subgroup reached the HbA1C goal of <7%. None of them had either symptomatic hypotension, hypoglycaemia, dyselectrolaemia, and decline in renal function. The drug was well received by most of the patients. ConclusionsDapagliflozin, an SGLT2i, should be used in symptomatic, refractory HFrEF patients despite the use of ARNI. The combination of ARNI and SGLT2i is well tolerated, but large, randomized trials are needed to prove this hypothesis.

Sodium and glucose cotransporter type 2 inhibitors: a new class of drugs for the treatment of diabetic and non-diabetic nephropathy

Inhibitors of renal sodium-glucose cotransporter type 2 (SGLT2) are a new class of antidiabetic drugs that have recently been introduced into clinical practice for the treatment of patients with type 2 diabetes mellitus. According to CREDENCE study, the inclusion of canagliflozin in drug therapy for patients with type 2 diabetes mellitus not only provides adequate control of blood glucose but also has a pronounced nephroprotective effect, which manifests in a significant reduction in the risk of progression of renal dysfunction in patients with stages 2, 3a and 3b CKD. The identification of nephroprotective effects in SGLT2 inhibitors, which is not related to their antihyperglycemic effect, suggests the possibility of using drugs of this class for drug therapy of patients with CKD of non-diabetic etiology. The review presents the data of clinical studies devoted to elucidating the participation of diuretic action and the associated decrease in blood pressure and venous stasis in the kidneys, improving glomerular hemodynamics and inhibiting the activity of intrarenal RAS in the mechanism of nephroprotective action of these drugs. Large-scale DAPA-CKD and EMPA-KIDNEY studies are currently underway, the results of which will provide information on the clinical efficacy and safety of dapagliflozin and empagliflozin in non-diabetic patients with the impaired renal function of varying severity, including those with stage 4 CKD. Initial data obtained in the DAPA-CKD trial indicated that dapagliflozin, when added to nephroprotective therapy, significantly improves renal outcomes not only in patients with type 2 diabetes but also in patients with CKD of non-diabetic origin, including those with glomerulonephritis, hypertensive nephropathy, and other kidney damage.

Efficacy and Safety of Dapagliflozin in Treatment Naive or Treatment Experienced Type 2 Diabetes Mellitus Patients from South Punjab, Pakistan

Efficacy and Safety of Dapagliflozin in Treatment Naive or Treatment Experienced Type 2 Diabetes Mellitus Patients from South Punjab, Pakistan

Efficacy and safety of dapagliflozin in the treatment of chronic heart failure: A protocol for systematic review and meta-analysis.

Background:As the last link in the chain of cardiovascular events, chronic heart failure (CHF) has high morbidity, high mortality, and poor prognosis. It is one of the main causes of death and disability worldwide. As a new drug for the treatment of chronic cardiovascular disease, dapagliflozin, the efficacy, and safety issues are still the focus of attention. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of dapagliflozin in the treatment of CHF.Methods:According to the search strategy, regardless of publication date or language, randomized controlled trials (RCTs) of dapagliflozin for CHF will be retrieved from 8 databases. First of all, the literature was screened according to the eligibility criteria, and use the Cochrane Collaboration's tool to assess the quality of the included literature. Then, using Rev Man 5.3 and STATA 14.2 software for traditional meta-analysis. Finally, the evaluation of the quality of the evidence and the strength of the recommendations will adopt the Grading of Recommendations, Assessment, Development and Evaluation method.Results:This study will evaluate the efficacy and safety of dapagliflozin for CHF, thereby providing more evidence support for clinical decision-making in CHF.Conclusion:Our research will provide more references for the clinical medication of patients with CHF.Protocol registration number:INPLASY202150046

Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial.

OBJECTIVEThe Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.RESEARCH DESIGN AND METHODSWe enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200–5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death.RESULTSOf 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes.CONCLUSIONSDapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.