Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Biological and trophic consequences of genetic introgression between endemic and invasive Barbus fishes.

Genetic introgression with native species is recognized as a detrimental impact resulting from biological invasions involving taxonomically similar invaders. Whilst the underlying genetic mechanisms are increasingly understood, the ecological consequences of introgression are relatively less studied, despite their utility for increasing knowledge on how invasion impacts can manifest. Here, the ecological consequences of genetic introgression from an invasive congener were tested using the endemic barbel populations of central Italy, where the invader was the European barbel Barbus barbus. Four populations of native Barbus species (B. plebejus and B. tyberinus) were studied: two purebred and two completely introgressed with alien B. barbus. Across the four populations, differences in their biological traits (growth, body condition and population demographic structure) and trophic ecology (gut content analysis and stable isotope analysis) were tested. While all populations had similar body condition and were dominated by fish up to 2 years of age, the introgressed fish had substantially greater lengths at the same age, with maximum lengths 410-460 mm in hybrids versus 340-360 mm in native purebred barbel. The population characterized by the highest number of introgressed B. barbus alleles (81 %) had the largest trophic niche and a substantially lower trophic position than the other populations through its exploitation of a wider range of resources (e.g. small fishes and plants). These results attest that the genetic introgression of an invasive congener with native species can result in substantial ecological consequences, including the potential for cascading effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-021-02577-6