Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria.

Aim: To examine the renal effects of sodium-glucose cotransporter-2 (SGLT2) inhibition among non-diabetic individuals with chronic kidney disease (CKD) in a real-world setting.

Methods: We collected de-identified data on adults without diabetes and with an estimated glomerular filtration rate (eGFR) of 25-60 mL/min/1.73 m, who initiated the SGLT2 inhibitors dapagliflozin or empagliflozin between September 2020 and November 2022 at Maccabi Healthcare Services, an Israeli health maintenance organization.

Pharmaceutical Agents as Potential Drivers in the Development of Early-Onset Colorectal Cancer: Case-Control Study.

Background: The incidence of early-onset colorectal cancer (EOCRC) rose abruptly in the mid 1990s, is continuing to increase, and has now been noted in many countries. By 2030, 25% of American patients diagnosed with rectal cancer will be 49 years or younger. The large majority of EOCRC cases are not found in patients with germline cancer susceptibility mutations (eg, Lynch syndrome) or inflammatory bowel disease.

Long-Term, Real-World Kidney Outcomes with SGLT2i versus DPP4i in Type 2 Diabetes without Cardiovascular or Kidney Disease.

Background: Contemporary guidelines recommend the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) independently of glycemic control in patients with type 2 diabetes and those with kidney disease, with heart failure, or at high risk of cardiovascular disease. Using a large Israeli database, we assessed whether long-term use of SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP4is) is associated with kidney benefits in patients with type 2 diabetes overall and in those without evidence of cardiovascular or kidney disease.

Methods: Patients with type 2 diabetes who initiated SGLT2is or DPP4is between 2015 and 2021 were propensity score-matched (1:1) according to 90 parameters.

Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.

Background: In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel.

Real-World Use of Alirocumab: Experience from a Large Healthcare Provider.

With the emerging use of anti-PCSK9 monoclonal antibodies for lowering low-density lipoprotein cholesterol (LDL-C) levels, real-world evidence (RWE) is needed to evaluate drug effectiveness. This study aimed to characterize new users of alirocumab and evaluate its effectiveness in achieving LDL-C target levels. Included were patients initiating treatment with alirocumab from 1 August 2016 to 1 May 2020, with blood lipids evaluations during baseline (180 days prior to therapy initiation) and after 120 (±60) days of follow-up.

Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.

Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors.

Pharmacologic Treatment of Type 2 Diabetes in the U.S., Sweden, and Israel.

Objective: To characterize and compare glucose-lowering medication use in type 2 diabetes in the U.S., Sweden, and Israel, including adoption of newer medications and prescribing patterns.

Temporal patterns selection for All-Cause Mortality prediction in T2D with ANNs.

Mortality prevention in T2D elderly population having Chronic Kidney Disease (CKD) may be possible thorough risk assessment and predictive modeling. In this study we investigate the ability to predict mortality using heterogeneous Electronic Health Records data. Temporal abstraction is employed to transform the heterogeneous multivariate temporal data into a uniform representation of symbolic time intervals, from which then frequent Time Intervals Related Patterns (TIRPs) are discovered.

All-cause mortality prediction in T2D patients with iTirps.

Mortality in the type II diabetic elderly population can sometimes be prevented through intervention, for which risk assessment through predictive modeling is required. Since Electronic Health Records data are typically heterogeneous and sparse, the use of Temporal Abstraction and time intervals mining to discover frequent Time Intervals Related Patterns (TIRPs) is employed. While TIRPs are used as features for a predictive model, the temporal relations between them in general, and among each TIRP's instances are not represented.

Epidemiology of the diabetes-cardio-renal spectrum: a cross-sectional report of 1.4 million adults.

Background: Type-2 diabetes (T2D), chronic kidney disease, and heart failure (HF) share epidemiological and pathophysiological features. Although their prevalence was described, there is limited contemporary, high-resolution, epidemiological data regarding the overlap among them. We aimed to describe the epidemiological intersections between T2D, HF, and kidney dysfunction in an entire database, overall and by age and sex.

Obesity in late adolescence and incident type 1 diabetes in young adulthood.

Aims/hypothesis: Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood.

Methods: All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia.

Validating the UK prospective diabetes study outcome model 2 using data of 94,946 Israeli patients with type 2 diabetes.

Aims: To externally validate the United Kingdom Prospective Diabetes Study (UKPDS) Outcome Model 2 (OM2) in contemporary Israeli patient populations.

Methods: De-identified patient data on demographics, time-varying risk factors, and clinical events of newly diagnosed type 2 diabetes patients were extracted from the Maccabi Healthcare Services (MHS) diabetes registry over years 2000-2013. Depending on the baseline risk, patients were categorized into low-risk and intermediate-risk groups.

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

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).

Short-Term Excess Healthcare Costs Associated with Cardiovascular Events Among Adults with Type 2 Diabetes in Israel: A Retrospective Cohort Study.

Objective: The aim was to characterise the short-term (up to 12 months) direct economic burden of new cardiovascular (CV) events among adults with type 2 diabetes (T2D) in Israel.

Methods: In this retrospective cohort study utilising the electronic health records of the Maccabi Healthcare Services, adults aged ≥ 21 years with T2D who experienced their first CV event (2013-2016) were identified via adjudicated enrolment in a CV registry. Wilcoxon rank-sum test estimated excess healthcare resource utilisation in three periods after the CV event: immediate (1 month; for all patients), acute (3 months; for survivors of 1 month of follow-up) and short-term (12 months; for survivors of 3 months of follow-up).

Association of sodium-glucose cotransporter-2 inhibitors with outcomes in type 2 diabetes with reduced and preserved left ventricular ejection fraction: Analysis from the CVD-REAL 2 study.

This study of real-world data from the Maccabi database in Israel compared the risk of heart failure hospitalization (HHF) or death in patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors versus other glucose-lowering drugs (OGLDs) according to baseline left ventricular (LV) ejection fraction (EF). After propensity-matching patients by baseline EF there were 10 614 episodes of treatment initiation; 57% had diabetes for >10 years, the mean glycated haemoglobin level was 66 mmol/mol (8.2%), ∼43% had cardiovascular disease, ∼7% had heart failure and ∼ 20% had chronic kidney disease.

Elevated Costs and Healthcare Resource Utilization in Patients With Type 2 Diabetes and Established Cardiovascular Disease in Israel.

Objectives: To evaluate excess healthcare resource utilization (HRU) and costs among patients with both type 2 diabetes (T2D) and established cardiovascular disease (CVD) relative to those with T2D only, in Israel.

Methods: A retrospective, observational, cohort study of adult patients with T2D from the Maccabi Healthcare Services in Israel who enrolled in a cardiovascular registry between 2013 and 2016 (pre-index date period). Patients with established CVD between 2013 and 2016 were propensity matched 1:2 to control patients without established CVD.

The effectiveness of insulin glargine 300 U/mL among type 2 diabetes patients: Analysis of a real-world data in Israel.

Aims: Randomized controlled trials have shown that insulin glargine 300 U/mL (Gla-300) has a more stable and prolonged glucose lowering effect among patients with type 2 diabetes (T2DM) compared to insulin glargine 100 U/mL (Gla-100), resulting in a reduced risk of hypoglycaemia while maintaining a similar efficacy of lowering HbA. We aimed to investigate if the effectiveness of Gla-300 is reproducible in real-world settings.

Material And Methods: In this retrospective cohort study, data from a large state-mandated health organization were used to identify adult T2DM patients who were previously on insulin and initiated Gla-300 therapy between 6/ 2016 and 12/2017.

Very Low Birth Weight Preterm Infants have Decreased Celiac Disease Autoimmunity During Childhood and Adolescence.

Little is known about the effect of prematurity on later development of celiac disease (CD). We conducted a retrospective analysis of real-world data examining the association between very low birth weight (VLBW) prematurity and later development of CD autoimmunity (CDA) in 3580 infants born between years 2000 and 2012 and their matched controls. At a median of 12 years, VLBW prematurity was negatively associated with later development of CDA with a cumulative prevalence of 5.

Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study.

Background: Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in routine clinical practice.

Methods: CVD-REAL 3 was a multinational observational cohort study in which new users of SGLT2 inhibitors and other glucose-lowering drugs with measurements of estimated glomerular filtration rate (eGFR) before and after (within 180 days) initiation were identified via claims, medical records, and national registries in Israel, Italy, Japan, Taiwan, and the UK.

Metabolic Control and Adherence to Therapy in Type 2 Diabetes Mellitus Patients Using IDegLira in a Real-World Setting.

Introduction: Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination (FRC) of basal insulin and glucagon-like protein-1 receptor agonist (GLP-1 RA) that has demonstrated glycemic and metabolic benefits in patients with type 2 diabetes mellitus (T2DM) in both randomized controlled trials and real-world studies. The impact of adherence to this medication and its effect on patients with T2DM who switch from loose-dose combination therapy to a FRC of insulin and GLP-1RA have not yet been reported. We have examined the metabolic effects and adherence to this medication in a real-life setting, in T2DM patients who initiated IDegLira therapy after being treated with other glucose-lowering drugs.

A Retrospective Database Study of Liraglutide Persistence Associated with Glycemic and Body Weight Control in Patients with Type 2 Diabetes.

Introduction: In both randomized controlled trials and real-world studies, liraglutide has demonstrated glycemic and body weight benefits in patients with type 2 diabetes. However, persistence with diabetes medication can be challenging. This study compared glycated hemoglobin (HbA) and other outcomes in patients with type 2 diabetes who continued treatment with liraglutide for over 12 months with those who discontinued treatment earlier, in a real-life setting.