Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Improving the assessment and management of obesity in UK children and adolescents: the PROMISE research programme including a RCT

BackgroundFive linked studies were undertaken to inform identified evidence gaps in the childhood obesity pathway.Objectives(1) To scope the impact of the National Child Measurement Programme (NCMP) (study A). (2) To develop a brief evidence-based electronic assessment and management tool (study B). (3) To develop evidence-based algorithms for identifying the risk of obesity comorbidities (study B). (4) To conduct an efficacy trial of the Healthy Eating and Lifestyle Programme (HELP) (study C). (5) To improve the prescribing of anti-obesity drugs in UK adolescents (study D). (6) To investigate the safety, outcomes and predictors of outcome of adolescent bariatric surgery in the UK (study E).MethodsFive substudies – (1) a parental survey before and after feedback from the National Childhood Measurement Programme, (2) risk algorithm development and piloting of a new primary care management tool, (3) a randomised controlled trial of the Healthy Eating and Lifestyle Programme, (4) quantitative and qualitative studies of anti-obesity drug treatment in adolescents and (5) a prospective clinical audit and cost-effectiveness evaluation of adolescent bariatric surgery in one centre.ResultsStudy A – before the National Childhood Measurement Programme feedback, three-quarters of parents of overweight and obese children did not recognise their child to be overweight. Eighty-seven per cent of parents found the National Childhood Measurement Programme feedback to be helpful. Feedback had positive effects on parental knowledge, perceptions and intentions. Study B – risk estimation models for cardiovascular and psychosocial comorbidities of obesity require further development. An online consultation tool for primary care practitioners is acceptable and feasible. Study C – the Healthy Eating and Lifestyle Programme, when delivered in the community by graduate mental health workers, showed no significant effect on body mass index at 6 months (primary outcome) when compared with enhanced usual care. Study D – anti-obesity drugs appear efficacious in meta-analysis, and their use has expanded rapidly in the last decade. However, the majority of prescriptions are rapidly discontinued after 1–3 months of treatment. Few young people described positive experiences of anti-obesity drugs. Prescribing was rarely compliant with the National Institute for Health and Care Excellence guidance. Study E – bariatric surgery appears safe, effective and highly cost-effective in adolescents in the NHS.Future work and limitationsWork is needed to evaluate behaviour and body mass index change in the National Childhood Measurement Programme more accurately and improve primary care professionals’ understanding of the National Childhood Measurement Programme feedback, update and further evaluate the Computer-Assisted Treatment of CHildren (CATCH) tool, investigate delivery of weight management interventions to young people from deprived backgrounds and those with significant psychological distress and obtain longer-term data on anti-obesity drug use and bariatric surgery outcomes in adolescence.Trial registrationCurrent Controlled Trials ISRCTN99840111.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 8, No. 3. See the NIHR Journals Library website for further project information.</jats:sec

BRANDEBURGO (Alemania). Mapas generales (1811). 1:90000

Relieve representado por normalesIndica cultivo

BRANDEBURGO (Alemania). Mapas generales (1811). 1:90000

Relieve representado por normalesIndica cultivos y el curso del rio con flechaEn el margen superior derecho N