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 <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >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 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<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

Searches for supersymmetry with the ATLAS detector using final states with two leptons and missing transverse momentum in root s=7 TeV proton-proton collisions

Results of three searches are presented for the production of supersymmetric particles decaying into final states with missing transverse momentum and exactly two isolated leptons, e or mu. The analysis uses a data sample collected during the first half of 2011 that corresponds to a total integrated luminosity of 1 fb(-1) of root s = 7 TeV proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider. Opposite-sign and same-sign dilepton events are separately studied, with no deviations from the Standard Model expectation observed. Additionally, in opposite-sign events, a search is made for an excess of same-flavour over different-flavour lepton pairs. Effective production cross sections in excess of 9.9 fb for opposite-sign events containing supersymmetric particles with missing transverse momentum greater than 250 GeV are excluded at 95% CL For same-sign events containing supersymmetric particles with missing transverse momentum greater than 100 GeV, effective production cross sections in excess of 14.8 fb are excluded at 95% CL The latter limit is interpreted in a simplified electroweak gaugino production model excluding chargino masses up to 200 GeV, under the assumption that slepton decay is dominant. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved