Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8):a double-blind, phase 3b, randomised controlled trial

Background: Existing guidelines for management of type 2 diabetes recommend a patient-centred approach to guide the choice of pharmacological agents. Although glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors are increasingly used as second-line agents, direct comparisons between these treatments are insufficient. In the SUSTAIN 8 trial, we compared the efficacy and safety of semaglutide (a GLP-1 receptor agonist) with canagliflozin (an SGLT2 inhibitor) in patients with type 2 diabetes.Methods: This was a double-blind, parallel-group, phase 3b, randomised controlled trial done at 111 centres in 11 countries. Eligible patients were at least 18 years old and had uncontrolled type 2 diabetes (HbA1c 7·0–10·5% [53–91 mmol/mol]) on stable daily metformin therapy. Patients were randomly assigned (1:1) by use of an interactive web response system to subcutaneous semaglutide 1·0 mg once weekly or oral canagliflozin 300 mg once daily. The primary endpoint was change from baseline in HbA1c, and the confirmatory secondary endpoint was change from baseline in bodyweight, both at week 52. The primary analysis population included all randomly assigned patients, using on-treatment data collected before initiation of rescue medication. The safety analysis was done on a population that included all patients exposed to at least one dose of trial product. The trial was powered for HbA1c and bodyweight superiority under reasonable assumptions. This trial is registered with ClinicalTrials.gov, NCT03136484.Findings: Between March 15, 2017, and Nov 16, 2018, 788 patients were randomly assigned to semaglutide 1·0 mg (394 patients) or canagliflozin 300 mg (394 patients). 739 patients completed the trial (367 in the semaglutide group and 372 in the canagliflozin group). From overall baseline mean, patients receiving semaglutide had significantly greater reductions in HbA1c and bodyweight than those receiving canagliflozin (HbA1c estimated treatment difference [ETD] −0·49 percentage points, 95% CI −0·65 to −0·33; −5·34 mmol/mol, 95% CI −7·10 to −3·57; p&lt;0·0001; and bodyweight ETD −1·06 kg, 95% CI −1·76 to −0·36; p=0·0029). Gastrointestinal disorders, most commonly nausea, were the most frequently reported adverse events with semaglutide, occurring in 184 (47%) of 392 patients; whereas infections and infestations (defined using the Medical Dictionary for Regulatory Activities, version 21.0), most commonly urinary tract infections, occurred more frequently with canagliflozin, in 136 (35%) of 394 patients. Premature treatment discontinuation because of adverse events occurred in 38 (10%) of 392 patients with semaglutide and in 20 (5%) of 394 patients with canagliflozin. One fatal adverse event confirmed unlikely to be caused by treatment occurred in the semaglutide group.Interpretation: Once-weekly semaglutide 1·0 mg was superior to daily canagliflozin 300 mg in reducing HbA1c and bodyweight in patients with type 2 diabetes uncontrolled on metformin therapy. These outcomes might guide treatment intensification choices.</p

A Novel HLA-A*0201 Restricted Peptide Derived from Cathepsin G Is an Effective Immunotherapeutic Target in Acute Myeloid Leukemia

Immunotherapy targeting aberrantly expressed leukemia associated antigens (LAA) has shown promise in the management of acute myeloid leukemia (AML). However, because of the heterogeneity and clonal evolution that is a feature of myeloid leukemia, targeting single peptide epitopes has had limited success, highlighting the need for novel antigen discovery. In this study, we characterize the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel target for AML immunotherapy

Technological advancements in the development of photochemical remediation for polychlorinated biphenyl contaminated soils

Bibliography: p. 255-288Some pages are in colour

Hydrodynamics and mass transfer in different zones of a three-phase fluidized bed

Bibliography: p. 82-87

Shipping sentiment and the dry bulk shipping freight market: new evidence from newspaper coverage

In this paper, a shipping sentiment index in the dry bulk market is constructed using computational text analysis from shipping news archives. Our news corpus consists of 11,296 dry bulk news headlines from two major shipping news websites from January 2014 to November 2020. The constructed monthly index does track closely with major dry bulk freight indices. Then, we investigate how the freight market responds, if at all, to sentiment shock and whether news sentiment helps predict freight rates. Specifically, impulse response analyses using vector autoregression (VAR) models are employed to examine the effect of sentiment shocks on freight indices. The predictive power of the constructed shipping sentiment index for future dry bulk freight rates is further investigated using a least absolute shrinkage and selection operation (LASSO) regression. To examine potential asymmetric relationship between dry bulk freight rates and news sentiment, copula models are then utilized. Results show that the constructed news sentiment index is a significant predictor for the future freight rates, especially in the Capesize market. The effect of sentiment shocks is relatively transitory and varies across different dry bulk sub-segments. Last but not least, the impact of news sentiment on the dry bulk freight rates is asymmetric and tends to be higher when the sentiment is extremely positive, and such tail dependence is more obvious for the larger Capesize segment. This study provides significant implications and decision support for shipping players