Sitagliptin and other ‘gliptins’ - why prescribe them?

Introduction In 2008, the Federal Drug Administration (FDA) required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase (DPP)-4 inhibitors (‘gliptins’). At present, there is contradictory evidence on whether the gliptins increase hospitalizations for heart failure. Areas covered This is an evaluation of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in high risk cardiovascular subjects with type 2 diabetes [1]. TECOS demonstrated non-inferiority for sitagliptin over placebo for the primary outcome, which was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. There was no difference in the rate of hospitalization for heart failure between sitagliptin and placebo. Expert Opinion Despite the results of TECOS, debate over the effects of sitagliptin on the rates of hospitalizations for heart failure continues with some recent studies suggesting increased rates. Recently, empagliflozin (an inhibitor of sodium-glucose cotransporter 2) has been shown to reduce cardiovascular outcomes in subjects with type 2 diabetes, including the rates of hospitalization for heart failure. In our opinion, these positive findings with empagliflozin suggest that it should be prescribed in preference to the gliptins, including sitagliptin, unless any positive cardiovascular outcomes are reported for the gliptins.

Characterization of the carbonic anhydrase gene family and other key osmoregulatory genes in Australian freshwater crayfish (genus Cherax)

Cherax quadricarinatus (Redclaw), C. destructor (Yabby) and C. cainii (Marron) are a group of economically important freshwater crayfish and have been developed for aquaculture production in many countries. As crayfish are farmed in a wide range of culture conditions, optimisation of water quality parameters, are crucial for their maximum growth performance. Previous reports have shown that fluctuations in water quality can negatively impact on growth of crayfish. Therefore, this project aims to identify and characterize the major genes that enable freshwater crayfish to persist in different water chemistries and evaluate their patterns of expression under different water parameters. Overall, this project found a number of candidate genes in all three species and determined that water chemistry had a strong influence on the expression of candidate genes. This information is important in the optimization of water quality parameters in freshwater crayfish aquaculture production.

Transcriptome analysis and characterisation of gill-expressed carbonic anhydrase and other key osmoregulatory genes in freshwater crayfish Cherax quadricarinatus

The pH and salinity balance mechanisms of crayfish are controlled by a set of transport-related genes. We identified a set of the genes from the gill transcriptome from a freshwater crayfish Cherax quadricarinatus using the Illumina NGS-sequencing technology. We identified and characterized carbonic anhydrase (CA) genes and some other key genes involved in systematic acid-base balance and osmotic/ionic regulation. We also examined expression patterns of some of these genes across different sublethal pH levels [1]. A total of 72,382,710 paired-end Illumina reads were assembled into 36,128 contigs with an average length of 800 bp. About 37% of the contigs received significant BLAST hits and 22% were assigned gene ontology terms. These data will assist in further physiological-genomic studies in crayfish.