scholarly journals Cardiorenal outcomes with sodium/glucose cotransporter-2 inhibitors in patients with type 2 diabetes and low kidney risk: real world evidence

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Meir Schechter ◽  
Cheli Melzer-Cohen ◽  
Aliza Rozenberg ◽  
Ilan Yanuv ◽  
Gabriel Chodick ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Propensity Score ◽  
Lower Risk ◽  
Urinary Albumin ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Infraction ◽  
Specific Outcome ◽  
End Stage

Abstract Background Randomized controlled trials showed that sodium/glucose cotransporter-2 inhibitors (SGLT2i) protect the heart and kidney in an array of populations with type 2 diabetes (T2D) and increased cardiorenal risk. However, the extent of these benefits also in lower kidney-risk T2D populations needs further investigation. Methods Members of Maccabi Healthcare Systems listed in their T2D registry who initiated new glucose lowering agents (GLA), were divided into SGLT2i initiators and other GLAs (oGLAs). Groups were propensity score-matched by baseline demographic and medical characteristics. Two composite cardiovascular outcomes were defined: all-cause mortality (ACM) or hospitalization for heart failure (hHF); and ACM, myocardial infraction (MI) or stroke. The cardiorenal outcome was: ACM, new end-stage kidney disease (ESKD) or  ≥  40% reduction from baseline estimated glomerular filtration rate (eGFR). Renal-specific outcome was new ESKD or  ≥  40% eGFR reduction. Single components of cardiovascular and kidney outcomes were also assessed. Three subgroup definitions of low baseline kidney-risk were used: eGFR  >  90 ml/min/1.73 m2; urinary albumin below detectable levels; and low risk according to Kidney Disease: Improving Global Outcomes (KDIGO) classification. Analyses were performed utilizing an unadjusted model, and a model adjusted to baseline eGFR and urinary albumin-to-creatinine ratio. Results Between April 1, 2015 and June 30, 2018; 68,187 patients initiated new GLAs — 11,321 SGLT2i initiators and 42,077 oGLAs initiators were eligible. Propensity score-matching yielded two comparable cohorts; each included 9219 participants. Median follow-up was 1.7 years. Compared to oGLAs, SGLT2i initiators had lower incidence of ACM or hHF [HR95%CI  =  0.62(0.51–0.75)]; ACM, MI or stroke [0.67(0.57–0.80)]; the cardiorenal outcome [0.65(0.56–0.76)]; and the renal-specific outcome [0.70(0.57–0.85)]. SGLT2i initiators also had lower risk for ACM, hHF and  ≥  30%,  ≥  40%,  ≥  50%,  ≥  57% eGFR reduction. No difference between groups was observed for MI or stroke. In the low baseline kidney-risk subgroups, SGLT2i initiation was generally associated with lower risk of the cardiovascular and cardiorenal outcomes, driven mainly by lower ACM incidence. Conclusions Our findings in the general population of patients with T2D demonstrates lower risk of cardiorenal outcomes associated with initiation of SGLT2i compared with oGLAs, including specifically in patients with low baseline kidney-risk.

scholarly journals Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jordi Real ◽  
Bogdan Vlacho ◽  
Emilio Ortega ◽  
Joan Antoni Vallés ◽  
Manel Mata-Cases ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Propensity Score ◽  
Lower Risk ◽  
Previous History ◽  
Incidence Rates ◽  
Real World Data

Abstract Background Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. Methods CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). Results After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31–0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47–0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52–0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54–0.80; p < 0.001). Conclusions In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

FC 063DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Niels Jong ◽  
Glenn Chertow ◽  
Fan Fan Hou ◽  
John McMurray ◽  
Ricardo Correa-Rotter ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Urinary Albumin ◽  
Creatinine Ratio ◽  
Once Daily ◽  
Diabetes Status ◽  
Subgroup Analyses

Abstract Background and Aims Reductions in albuminuria are consistently associated with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes. Whether this effect persist in patients with chronic kidney disease (CKD) with and without diabetes is unknown. We therefore assessed and compared the effects of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes from the DAPA-CKD trial. Method We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified exploratory outcome. We used regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to micro- or normoalbuminuria (&lt;300 mg/g), and progression in UACR stage, defined as a transition from non-nephrotic (&lt;3000 mg/g) to nephrotic range albuminuria (≥3000 mg/g), as additional endpoints. Subgroup analyses were performed according to baseline type 2 diabetes status. Results Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3% (95% confidence interval [CI] 25.2, 33.1; p&lt;0.001), with a 35.1% (95%CI 30.6, 39.4) reduction in patients with type 2 diabetes and 14.8% (95%CI 5.9, 22.9) reduction in patients without type 2 diabetes (p for interaction &lt;0.001). Among 3860 patients with UACR ≥300 mg/g at baseline, dapagliflozin significantly increased the likelihood of regression in UACR stage (hazard ratio [HR] 1.81; 95%CI 1.60, 2.05). The corresponding HRs for patients with and without type 2 diabetes were 2.06 (95%CI 1.78, 2.39) and 1.33 (95%CI 1.07, 1.66), respectively (p for interaction 0.001). Among 3820 patients with UACR &lt;3000 mg/g at baseline, dapagliflozin significantly decreased the risk of nephrotic range albuminuria (HR 0.41; 95%CI 0.32, 0.52). The corresponding HRs for patients with and without type 2 diabetes were 0.39 (95%CI 0.29, 0.51) and 0.50 (95%CI 0.30, 0.82), respectively (p for interaction 0.401). Conclusion In patients with CKD with and without type 2 diabetes dapagliflozin significantly reduced albuminuria, with a larger reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR suggest that part of dapagliflozin’s protective effect in patients without diabetes is mediated through pathways unrelated to UACR reduction.

scholarly journals Effect of sodium-glucose cotransporter 2 inhibitor in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a propensity score-matched analysis of real-world data

2021 ◽  
Vol 12 ◽  
pp. 204201882110002
Author(s):  
Taeang Arai ◽  
Masanori Atsukawa ◽  
Akihito Tsubota ◽  
Shigeru Mikami ◽  
Hiroki Ono ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Propensity Score ◽  
Fatty Liver Disease ◽  
Liver Inflammation ◽  
Alcoholic Fatty Liver ◽  
Sodium Glucose Cotransporter ◽  
Alcoholic Fatty Liver Disease

Background: Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM. Methods: This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors. Results: The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1–6.7 kPa) ( p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight ( p < 0.001), alanine aminotransferase ( p = 0.02), uric acid ( p < 0.001), and Fibrosis-4 (FIB-4) index ( p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group ( p < 0.001). Conclusion: SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

scholarly journals Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study

2021 ◽  
Vol 9 (1) ◽  
pp. e001765
Author(s):  
Gábor Sütő ◽  
Gergő A Molnár ◽  
Gyorgy Rokszin ◽  
Ibolya Fábián ◽  
Zoltan Kiss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
All Cause Mortality

IntroductionMortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied.Research design and methodsPatients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model.ResultsAfter propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p<0.0001) were lower in the SGLT2i population compared with DPP-4i. Risk of LLA was higher in the SGLT2i group (HR, 1.35; 95% CI 1.03 to 1.77; p=0.0315). SGLT2i in combination with DPP-4i results in lower all-cause mortality (HR, 0.46; 95% CI 0.31 to 0.67; p=0.0001), with a lower trend in stroke, LLA, HHF and cancer, but without any statistical difference.ConclusionsSGLT2i treatment leads to a lower risk of overall mortality, HHF and cancer when compared with DPP-4i treatment. Adding SGLT2i to DPP-4i instead of switching from DPP-4i to SGLT2i further lowers the risk of all-cause mortality.

Sodium–glucose cotransporter-2 inhibitors: where and when?

2021 ◽  
Author(s):  
Martin R Cowie
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Glycaemic Control ◽  
Improve Outcome ◽  
Is Implementation ◽  
Sodium Glucose Cotransporter

Tweetable abstract Sodium–glucose cotransporter-2 inhibitors not only improve glycaemic control in Type 2 diabetes mellitus but convincingly improve outcome for everyone with HFrEF and albuminuric kidney disease. Trials then license – now all we need is implementation

Type 2 diabetes in patients with end‐stage kidney disease: influence on cardiovascular disease‐related mortality risk

2018 ◽  
Vol 209 (10) ◽  
pp. 440-446 ◽  
Author(s):  
Wai H Lim ◽  
David W Johnson ◽  
Carmel Hawley ◽  
Charmaine Lok ◽  
Kevan R Polkinghorne ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Kidney Disease ◽  
Mortality Risk ◽  
End Stage Kidney Disease ◽  
End Stage ◽  
Related Mortality

scholarly journals Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the CARMELINA randomized trial

2020 ◽  
Author(s):  
Vlado Perkovic ◽  
Robert Toto ◽  
Mark E Cooper ◽  
Johannes FE Mann ◽  
Julio Rosenstock ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Secondary Analysis ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
First Occurrence ◽  
Outcome Trial ◽  
End Stage ◽  
Reduced Kidney Function

<b>Objective</b> <p>Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular and kidney outcomes across baseline eGFR categories (≥ 60, 45-<60, 30-<45 and < 30 ml/min/1.73 m<sup>2</sup>) in CARMELINA, a cardio-renal placebo-controlled outcome trial of the DPP-4 inhibitor linagliptin (NCT01897532).</p> <p><b>Research Design and Methods</b></p> <p>Participants with cardiovascular disease (CVD) and/or CKD were included. The primary outcome was time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE), with a secondary outcome renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other endpoints included progression of albuminuria, change in HbA1c and adverse events (AEs) including hypoglycemia. </p> <p><b>Results</b></p> <p>6979 subjects (mean age 65.9 years, eGFR 54.6 ml/min/1.73m<sup>2</sup>, 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared to placebo did not affect the risk for 3P-MACE (HR.1.02 [95% CI, 0.89, 1.17]), or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction p-values > 0.05). Regardless of eGFR, albuminuria-progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced between groups overall and across eGFR categories. </p> <p><b>Conclusions </b></p> <p>Across all GFR categories, in participants with type 2 diabetes and CKD and/or CVD, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c, and no difference in AEs was observed.</p>

Sign in / Sign up

Export Citation Format

Share Document