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OBJECTIVE: The study was undertaken because it was unknown whether the duration of type 2 diabetes modifies the effects of sodium–glucose cotransporter 2 inhibitor canagliflozin on cardiovascular (CV) and kidney outcomes. RESEARCH DESIGN AND METHODS: This post hoc analysis of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program (N = 10,142) and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial (N = 4,401) evaluated hazard ratios and 95% CIs using Cox proportional hazards for the effects of canagliflozin on CV and kidney outcomes, including progression and regression of albuminuria over 5-year intervals of disease duration. RESULTS: Canagliflozin had ranges of benefit across intervals of diabetes duration, with no heterogeneity for major adverse CV events, CV death or heart failure hospitalization, and kidney failure requiring therapy or doubling serum creatinine. Furthermore, canagliflozin reduced albuminuria progression and increased albuminuria regression with no interaction across all diabetes duration subgroups. CONCLUSIONS: Our findings suggest that earlier treatment with canagliflozin confers consistent cardiorenal benefits to individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

In addition, generalizability of the results may be limited to individuals with previous CV events, high CV risk or nephropathy, similar to the patients enrolled in the CANVAS programme and CREDENCE trial. This post-hoc analysis assessed the effects of canagliflozin versus placebo on CV and kidney outcomes in patients with T2DM and high CV risk, and/or chronic kidney disease according to baseline treatment target achievement and risk factors. Keywords: canagliflozin; cardiovascular disease; diabetic nephropathy; type 2 diabetes EN canagliflozin cardiovascular disease diabetic nephropathy type 2 diabetes 2038 2042 5 06/06/23 20230701 NES 230701 BACKGROUND Management of type 2 diabetes mellitus (T2DM), a progressive metabolic disorder associated with substantial cardiovascular (CV) and kidney complications, includes risk factor optimization of glucose, blood pressure (BP) and lipids. [Extracted from the article]

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long‐term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time‐to‐event models were used to quantify the association between plasma exposure and long‐term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28–0.85) for kidney events and 1.13 (95% CI: 1.03–2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population. [ABSTRACT FROM AUTHOR]

Aim: To better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 in Ontario, Canada. Materials and Methods: We used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m2 and adverse cardiovascular co‐morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes. Results: While the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5‐year period (2011‐2012 to 2015‐2016), the prevalence of eGFR < 90 mL/min/1.73 m2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2‐year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes. Conclusions: This real‐world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m2, and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes‐related complications. [ABSTRACT FROM AUTHOR]

Introduction: First Nations communities are known to have high rates of diabetes. The rural First Nations communities in northwest (NW) Ontario are particularly affected. Regional studies in 1985 and 1994 found a high prevalence of diabetes. More recently, they are estimated to have the highest prevalence in Ontario at 19%, double the provincial norm. The purpose of this study is to examine the epidemiology and prevalence of diabetes in the total population and cardiovascular comorbidities in the adult population of 25 First Nations communities in NW Ontario. Methods: This retrospective diabetes prevalence study used primary care electronic medical record data for a 3-year period, 1 August 2014--31 July 2017. Diabetes prevalence was calculated for both the total and the adult (18+) populations and comorbid hypertension and dyslipidaemia were identified in adults. Results: The age-adjusted diabetes prevalence for the total population was 15.1% versus a Canadian prevalence of 8.8%. The age-adjusted adult prevalence was 14.1%, double Canada's average of 7.1%. The average age of adults with diabetes was 52 years (±14.9); 57% were female. Comorbid hypertension (58%) and dyslipidaemia (73%) were common. Metformin was the most commonly used medication (58%), followed by insulin/analogues (23%) and sulphonylureas (13%). Conclusion: The diabetes prevalence in the First Nations population of NW Ontario is double Canada's norm. Addressing it will require addressing relevant social determinants of health, including poverty and food security. [ABSTRACT FROM AUTHOR]

Aims: Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin‐to‐creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit. Materials and Methods: SONAR is a randomized, double‐blind, placebo‐controlled trial with approximately 3500 participants who have stage 2–4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin‐angiotensin system inhibitor. Results: After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non‐responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end‐stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05). Conclusion: SONAR aims to determine whether atrasentan added to guideline‐recommended therapies safely reduces the risk of CKD progression and delays the onset of end‐stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial “surrogate” response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

The article offers information on the theories of doctors related to the need of appropriate blood pressure targets for patients suffering from hypertension and diabetes. It discusses the possibility of adverse cardiovascular events for patients suffering from both hypertension and diabetes which also increases the possibility of stroke and myocardial infarction.

Background: The rising prevalence of type 2 diabetes underlines the importance of secondary strategies for the prevention of target organ damage. While access to diabetes education centers and diabetes intensification management has been shown to improve blood glucose control, these services are not available to all that require them, particularly in rural and northern areas. The provision of these services through the Home Care team is an advance that can overcome these barriers. Transfer of blood glucose data electronically from the home to the health care provider may improve diabetes management. Methods and design: The study population will consist of patients with type 2 diabetes with uncontrolled A1c levels living on reserve in the Battlefords region of Saskatchewan, Canada. This pilot study will take place over three phases. In the first phase over three months the impact of the introduction of the Bluetooth enabled glucose monitor will be assessed. In the second phase over three months, the development of guidelines based treatment algorithms for diabetes intensification will be completed. In the third phase lasting 18 months, study subjects will have diabetes intensification according to the algorithms developed. Discussion: The first phase will determine if the use of the Bluetooth enabled blood glucose devices which can transmit results electronically will lead to changes in A1c levels. It will also determine the feasibility of recruiting subjects to use this technology. The rest of the Diabetes Risk Evaluation and Management Tele-monitoring (DreamTel) study will determine if the delivery of a diabetes intensification management program by the Home Care team supported by the Bluetooth enabled glucose meters leads to improvements in diabetes management. Trial Registration: Protocol NCT00325624 [ABSTRACT FROM AUTHOR]

Objectives: For patients with type 2 diabetes, newer antihyperglycaemic agents (AHA), including the dipeptidyl peptidase IV inhibitors (DPP4i), glucagon‐like peptide‐1 receptor agonists (GLP1RA) and sodium glucose co‐transporter 2 inhibitors (SGLT2i) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin. However, it is not clear how AHA compare to placebo on risk of any hypoglycaemia. This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo. Design: A systematic review and meta‐analysis was conducted of randomized, placebo‐controlled trials ≥12 weeks in duration. MEDLINE, Embase and the Cochrane Library were searched up to April 16, 2019. Studies allowing use of other diabetes medications were excluded. Mantel‐Haenszel risk ratio with 95% confidence intervals were used to pool estimates based on class of AHA and number of concomitant therapies used. Patients: Eligible studies enrolled patients with type 2 diabetes ≥18 years of age. Results: 144 studies met our inclusion criteria. Any hypoglycaemia was not increased with AHA when used as monotherapy (DPP4i (RR 1.12; 95% CI 0.81‐1.56), GLP1RA (1.77; 0.91‐3.46), SGLT2i (1.34; 0.83‐2.15)), or as add‐on to metformin (DPP4i (0.95; 0.67‐1.35), GLP1RA (1.24; 0.80‐1.91), SGLT2i (1.29; 0.91‐1.83)) or as triple therapy (1.13; 0.67‐1.91). However, metformin monotherapy (1.73; 1.02‐2.94) and dual therapy initiation (3.56; 1.79‐7.10) was associated with an increased risk of any hypoglycaemia. Severe hypoglycaemia was rare not increased for any comparisons. Conclusions: Metformin and the simultaneous initiation of dual therapy, but not AHA used alone or as single add‐on combination therapy, was associated with an increased risk of any hypoglycaemia relative to placebo. [ABSTRACT FROM AUTHOR]

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1·73 m2 of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days) or end-stage kidney disease (eGFR <15 mL/min per 1·73 m2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532.Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4-2·9). 79 (6·0%) of 1325 patients in the atrasentan group and 105 (7·9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0·65 [95% CI 0·49-0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%) of 1325 patients in the atrasentan group and 34 (2·6%) of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85-2·07]; p=0·208). 58 (4·4%) patients in the atrasentan group and 52 (3·9%) in the placebo group died (HR 1·09 [95% CI 0·75-1·59]; p=0·65).Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease.Funding: AbbVie. [ABSTRACT FROM AUTHOR]