Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

AIMS: To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. METHODS: We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline. RESULTS: Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12‐week reductions in albuminuria compared with placebo: −33.2% [95% confidence interval (CI) −45.4, −18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: −23.5% (95% CI −37.6, −6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal‐related adverse events were observed in any group. CONCLUSIONS: Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin‐angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin‐induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long‐term renal and cardiovascular risk

Helicobacter pylori (H pylori) infection in Greece: the changing prevalence during a ten-year period and its antigenic profile

BACKGROUND: To evaluate changes in H pylori infection prevalence in Greece during a ten-year period, and to examine its antigenic profile. METHODS: Three groups of patients were studied. Group O-87: Banked serum samples of 200 consecutive adult outpatients, from the Hepato-Gastroenterology clinic of a teaching hospital at Athens, collected in 1987. Group O-97: Serum samples of 201 similarly selected outpatients from the same Unit, collected in 1997. Group BD-97: Serum samples of 120 consecutive blood donors from the same hospital, collected in 1997. H pylori IgG antibody seroprevalence was studied by a quantitative ELISA. Antigenic profile was studied by western-blot IgG assay, in 62 IgG positive patients of O-97 and BD-97. Results were analyzed by conventional statistics and multivariate regression analysis. RESULTS: The H pylori seroprevalence increased with age in the three tested groups. In O-97, seroprevalence did not differ from that, in BD-97. On the contrary, there was a significant decrease in seropositivity between O-87 and O-97 (59.5% vs 49.2%, p = 0.039). Multiple regression analysis showed that age over 35 years (OR:3.45, 95% CI:1.59–7.49, p = 0.002) and year of patients' selection – that is 1987 or 1997 – (OR:1.73, 95% CI:1.14–2.65 for 1987, p = 0.010), were independent risk factors of H pylori infection. The seroprevalence of CagA+ and VacA+ strains was 77.4% and 58.5%, respectively, and type I(CagA+/VacA+) strains were significantly more common than type II(CagA-/VacA-) strains (59.7% vs 22.6%, p < 0.001). CONCLUSIONS: During a ten-year period, we found a significant decrease of H pylori infection in Greece and our data support the birth cohort phenomenon as an explanation for the age-dependent increase of H pylori infection. The prevalence of CagA and/or VacA positive strains is relatively high, in a country with low incidence of gastric cancer

Dapagliflozin and cardiovascular outcomes in type 2 diabetes

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium– glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], <1.3; P<0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P=0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P=0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3% vs. 0.1%, P=0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P<0.001). CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARE–TIMI 58 ClinicalTrials.gov number, NCT01730534.