scholarly journals Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

Diabetes Care ◽  
2021 ◽  
pp. dc211081
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  
2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>


2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>


Drugs ◽  
2021 ◽  
Author(s):  
Marc Evans ◽  
Angharad R. Morgan ◽  
Martin B. Whyte ◽  
Wasim Hanif ◽  
Stephen C. Bain ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
James Burton ◽  
Sebastian Walpen ◽  
Sandrine Danel ◽  
Lucy Snowdon ◽  
Bernd Schroeppel

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is a common yet under-recognised condition in patients with CKD undergoing haemodialysis (HD), in whom it is associated with reduced health-related quality of life (HRQoL), poor sleep quality, and a greater risk of depression. This real-world study obtained insights from nephrologists in Europe and Australia into the current practices, attitudes and unmet medical needs relating to the diagnosis and treatment of CKD-aP. Method Qualitative data were obtained from structured interviews conducted Oct–Nov 2019 with 72 nephrologists from France, Germany, Italy, Spain, UK and Australia (n=12 in each country). Quantitative data relating to diagnostic/treatment practices for CKD-aP were collected May–July 2020 by a 20-minute physician survey and collection of patient record forms (PRF). The survey was completed by 301 nephrologists from France (n=50), Germany (n=56), Italy (n=58), Spain (n=55), UK (n=52), and Australia (n=30). Respondents’ level of agreement was assessed using a 7-point scale, from 1 (do not agree at all) to 7 (strongly agree). PRF data were also captured for 1435 HD patients with CKD-aP from all countries. All nephrologists who completed the interviews and surveys were currently treating &gt;5 HD patients with CKD-aP. Results Most nephrologists (75%) agreed that CKD-aP is under-diagnosed in HD patients, which is mainly driven by the lack of systematic screening by nephrologists and under-reporting of the condition by patients. The main barriers to screening for CKD-aP identified by nephrologists included the lack of diagnostic guidelines and absence of standardised pruritus intensity scales to consistently diagnose and classify CKD-aP severity. The majority (74%) agreed new clinical guidelines for nephrologists are needed to aid diagnosis. Nephrologists perceived that on average ∼34% of their HD patients experienced CKD-aP, and that 55% of them had moderate-severe symptoms. However, most nephrologists (79%) do not use any itch scales in clinical practice and 71% agreed a consistent international scale to diagnose CKD-aP is needed. 80% of nephrologists agreed diagnosis of CKD-aP is usually patient-driven, indicating there is a reliance on patients mentioning their symptoms. Less than half of nephrologists (46%) agreed that CKD-aP was easy to diagnose by clinical observation alone. The lack of targeted treatment guidelines and approved therapies for CKD-aP leads to an inconsistent, fragmented approach to management. Analysis of prescription data captured in the PRFs of 1435 HD patients with CKD-aP showed treatment in current clinical practice relies on incremental add-on therapy. The majority of patients (∼85-90%) receiving second- or subsequent lines of therapy for CKD-aP were prescribed combinations of different treatments. Commonly prescribed (off-label) medications for CKD-aP included antihistamines, moisturizers/emollients, corticosteroids and gabapentinoids. However, there was no single standard of care for the treatment of CKD-aP, highlighting the uncertainties nephrologists face relating to best treatment practice. Most nephrologists (72%) agreed that treatment options are very limited for patients with bothersome CKD-aP, and the survey responses indicated a high unmet need for novel treatments. The majority of nephrologists felt a major improvement was needed over current treatments, particularly in terms of improved efficacy for reduction of itch intensity (62%) and the ability to improve the patient HRQoL (57%). Conclusion This real-world international survey study of nephrologists showed that CKD-aP is a frequent, but under-diagnosed condition affecting many HD patients, with a lack of effective treatment options. Furthermore, there is an urgent need to develop guidelines to assist in the diagnosis of CKD-aP and new targeted treatment options that are both effective and well tolerated.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
L. Zanoli ◽  
A. Granata ◽  
P. Lentini ◽  
S. Rastelli ◽  
P. Fatuzzo ◽  
...  

SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD) the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.


Pharmacia ◽  
2021 ◽  
Vol 68 (3) ◽  
pp. 591-596
Author(s):  
Stefan Balkanski

Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitors used in the treatment of patients with type 2 diabetes. An aryl glycoside with significant effect as glucose-lowering agents, Dapagliflozin also has indication for patients with Heart Failure and Chronic Kidney Disease. This review examines the structure, synthesis, analysis, structure activity relationship and uses of the product. The studies behind this drug have opened the doors for the new line of treatment – a drug that reduces blood glucoses, decreases the rate of heart failures, and has a positive effect on patients with chronic kidney disease.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2350-PUB
Author(s):  
TAKAHIRO TOSAKI ◽  
SHIORI TOGA SATO ◽  
MASAKI KONDO ◽  
YUICHIRO YAMADA ◽  
AKEMI INAGAKI ◽  
...  

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