Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial.

BACKGROUND: The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. METHODS: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. FINDINGS: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62-0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). INTERPRETATION: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. FUNDING: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial

BACKGROUND AND OBJECTIVES: In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with type 2 diabetes, established atherosclerotic cardiovascular disease, and eGFR≥30 ml/min per 1.73 m2 at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. Post hoc, we analyzed cardiovascular and kidney outcomes, and safety, using the two-dimensional KDIGO classification framework. RESULTS: Of 6952 patients with baseline eGFR and urinary albumin-creatinine ratio values, 47%, 29%, 15%, and 8% were classified into low, moderately increased, high, and very high KDIGO risk categories, respectively. Empagliflozin showed consistent risk reductions across KDIGO categories for cardiovascular outcomes (P values for treatment by subgroup interactions ranged from 0.26 to 0.85) and kidney outcomes (P values for treatment by subgroup interactions ranged from 0.16 to 0.60). In all KDIGO risk categories, placebo and empagliflozin had similar adverse event rates, the notable exception being genital infection events, which were more common with empagliflozin for each category. CONCLUSIONS: The observed effects of empagliflozin versus placebo on cardiovascular and kidney outcomes were consistent across the KDIGO risk categories, indicating that the effect of treatment benefit of empagliflozin was unaffected by baseline CKD status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: EMPA-REG OUTCOME, NCT01131676

Effect of switching from pioglitazone to the sodium glucose co-transporter-2 inhibitor dapagliflozin on body weight and metabolism-related factors in patients with type 2 diabetes mellitus : An open-label, prospective, randomized, parallel-group comparison trial

The effects of dapagliflozin (DAP) and pioglitazone (PIO) on body weight and glycaemic control were compared in patients with type 2 diabetes mellitus. Seventy-one patients on PIO were either switched to DAP (n = 36) at 5 mg per day or continued on PIO (n = 35). Primary endpoints were superiority of body weight loss and non-inferiority of HbA1c level after 24 weeks with DAP. Body weight decrease was greater with DAP than with PIO (75.3 ± 14.9 to 71.3 ± 15.1 kg vs. 74.7 ± 13.8 to 75.2 ± 13.9 kg; P < 0.01). Change in the HbA1c level was comparable (P = 0.64). The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and urinary albumin : creatinine ratio (ACR) decreased only with DAP (NT-proBNP, P < 0.01; ACR, P = 0.02), and the change in NT-proBNP correlated negatively with baseline NT-proBNP level (ρ = -0.68, P < 0.01) and log-converted ACR (ρ = -0.35, P < 0.05). DAP promotes body weight loss in type 2 diabetes mellitus and may decrease fluid retention, thus reducing the occurrence of cardiovascular events

A STUDY ON INDUSTRIAL SAFETY MANAGEMENT IN YANGON INDUSTRIAL ZONES (CASE STUDY: EASTERN DISTRICT INDUSTRIAL ZONES, YANGON)

A safety management system in developing or transition period, industrial zones can be important issues for any industry, no matter its size or what it produces. Constantly, evolving policies and laws make occupational health and safety increasingly important for every organization. This study is to identify the present condition of voluntary or government supervised industrial safety management activities of industries in Yangon industrial zones. This study is based on descriptive method using survey data. Most of the industrial enterprises have some safety elements such as policies, objectives, procedure, reporting and learning. Almost all of industrial enterprises realise that tripartite management activities are effective safety management activities not to occur any accidents in industries. Most of the employers used to provide some sort of safety facilities and ensure proper and constant maintenance of equipment and tools, proper guard of moveable and dangerous parts of machines A few amount of safety managers always organize pep talk and organize workplace safety meetings. Almost all of industries have and achieve the permits or licenses and also have being inspected and supervised annually by regulatory bodies which relevant to industrial safety such as Factories and General Labor Laws Inspection Department, Fire Services Department and Electrical Inspectorate. But some industrial enterprises do not have boiler licenses from Boiler Inspectorate although they had used boiler in their production process

A STUDY ON AGRICULTURAL PRODUCTIVITY THROUGH IRRIGATION IMPROVEMENT (A CASE STUDY OF POST-CYCLONE NARGIS AYEYARWADY DELTA)

The aim of this study is to analyze the potential effects of irrigation facilities namely polder embankment, sluice gates and drainage systems on the agricultural productivities in Ayeyarwady Delta region, post-Cyclone Nargis, 2008. The qualitative key informant interviews and quantitative descriptive method are used in this study, implying basically on primary data and secondary data. A sample household survey is conducted on 34 villages covered by polders in six townships namely Ngaputaw, Labutta, Bogalay, Pyapon, Daydaye and Kyaiklatt from Delta region. The questionnaire is applied in the survey to attain the potential effects of construction and rehabilitation of polder system on the agricultural productivity. The Delta is fertile and beneficial for above 30 percent of country’s rice and fish production. But it is low lying virtually without protecting polders. This produce very vulnerable to rising high sea level by storm surges and may coincide with salinity intrusion and river flood, resulting in crop losses and decreased yields. The study found that polder embankment supply expansion of cultivable land with the major reclamation for rain fed paddy and tidal irrigation for summer paddy cultivation. The potential effects of irrigation facilities can also be perceived in sluices and drainages affect to decrease soil salinity and to better yield per unit area as well as to retain fresh water for cropping intensity by prolonging the growing season. The study areas have potential for further development of agriculture sector and its endeavour to food security, employment and national economy through irrigation improvement

A STUDY ON EFFECTIVENESS OF COMMUNITY BASED DISASTER RISK REDUCTION ACTIVITIES IN MYANMAR CASE STUDY: PUAKTAW TOWNSHIP, RAKHINE STATE

The objective of this thesis is to analyze the effectiveness of the activities of Community Based Disaster Risk Reduction Programmes by Malteser International and the assessment on the hazard exposure and change, household level preparedness, community level preparedness and community engagement and feedback of the community in Pauktaw Township. This study uses a descriptive method. CBDRR programmes aim to reduce the vulnerability and enhance the resilience of communities to the adverse effects of natural hazards. A sample of 322 respondents was selected from 5 villages in Pauktaw Township. The project was effective in promoting advances in household preparedness. The sampled communities had sound early warning systems in place, and at least half of the original committee members were still active. This area requires further refining to ensure communities conduct their own simulations independently and regularly. There were some fencing issues, and cattle destroyed several mangrove plantations. The community had no systemic waste disposal and dumped most of their waste into the river, including plastics. School based disaster risk reduction could teach students about conservation and pollution

AN ANALYSIS OF COMMUNITY LED TOTAL SANITATION TO CERTIFICATION OF OPEN DEFECATION FREE VILLAGES (Case Study: Selected Villages in Myin Mu Township)

Water, Sanitation and Hygiene is at the centre of 2030 ambitious new development agenda; with a distinct sector goal, Sustainable Development Goal - SDG 6 that envisions universal, sustainable, and equitable access to safe drinking water, sanitation and hygiene, and the elimination of open defecation by 2030. This thesis aims to assess community-level factors associated with sustaining Open Defecation Free (ODF) status to inform post-Open Defecation Free programming. Both quantitative and qualitative research design and descriptive method are used for this thesis. Simple Random Sampling was used to select six sample villages from 80 villages of Myin Mu Township in Sagaing Region. Systematic Sampling was used to select sample households for personal interview in selected sample villages. This study found that the respondents understand the importance of sanitation for their health, improved socio-economic status and are aware of the sustainability of latrines and ODF status of their village. This study found that the sustainability of ODF status has to be maintained by well-established/robust community mechanism and the respondents acknowledge the critical role and importance of the leadership of village leaders or village development committee

A STUDY ON STATUS OF TOWNSHIP ADMINISTRAION (AFTER 1988) (Case Study: Western and Northern Districts in Yangon Region)

Township administration plays a very important role in providing public services of the government to the glass root people. The objectives of the study are to identity the status of township administration and to examine the changes of township governance between the State Law and Order Restoration Council/ the State Peace and Development Council and the democratic government. Descriptive method is used in this study. The quantitative research is conducted by distribution of questionnaires to 195 respondents. The study only focuses on the civil services in township level from 13 townships of the Yangon western and northern districts. It was found that bureaucratic mechanism is being exercised in the township governance; SLORC/SPDC was military government from 1988 to 2011 and there was no transparency and accountability but also taking into account the feedback of people. The military officials are supreme decision makers. They only abided by the directive of their upper levels merely rules and regulations. TLORC or TPDC was entitled to supervise, control and inspect the activities of township department. Democratic government has evolved as of 2011, township administrator continues to perform township governance and TGAD is a primary interface and plays a dual role. In providing for public services, township departments not only perform the responsibilities in accordance with rules and regulations but also have to take into account the feedback of people. Some of township committees exercise their respective statutory law. Township administrator only convenes and cooperates with the inter departments for implementing township governance

EMPA Jahresbericht 2011

ISSN:1424-217