The SGLT2 inhibitor empagliflozin for the treatment of type 2 diabetes mellitus: A bench to bedside review

INTRODUCTION: The treatment of type 2 diabetes mellitus (T2DM) continues to pose challenges for clinicians and patients. The dramatic rise in T2DM prevalence, which has paralleled the rise in obesity, has strained the healthcare system and prompted the search for therapies that not only effectively treat hyperglycemia, but are also weight neutral or promote weight loss. In most clinical situations after diagnosis, patients are advised to adopt lifestyle changes and metformin is initiated to help control blood glucose levels. However, metformin may not be tolerated, or may not be sufficient for those with higher glucose levels at diagnosis. Even among those who have initial success with metformin, the majority eventually require one or more additional agents to achieve their treatment goals. Because T2DM is a progressive disease, the requirement for combination treatment escalates over time, driving the need for therapies with complementary mechanisms of action. METHODS AND RESULTS: Online public resources were searched using “empagliflozin”, identifying 32 articles in PubMed, and 12 abstracts presented at the 2013 American Diabetes Association meeting. Peer-reviewed articles and abstracts describing preclinical studies and clinical trials were retrieved, and relevant publications included in this review. Trials registered on clinicaltrials.gov were searched for ongoing empagliflozin studies. CONCLUSION: The sodium–glucose co-transporter 2 (SGLT2) inhibitors are of great interest since they provide a novel, insulin-independent mechanism of action. The SGLT2 inhibitor empagliflozin has demonstrated promising pharmacodynamic and pharmacokinetic properties. In clinical trials, empagliflozin has demonstrated a good efficacy and safety profile in a broad range of patients with T2DM, and appears to be an attractive adjunct therapeutic option for the treatment of T2DM. Ongoing trials, including patients with T2DM and comorbidities such as hypertension, are expected to provide important additional data, which will further define the role of empagliflozin in a growing movement toward individualized approaches to diabetes care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13300-014-0063-1) contains supplementary material, which is available to authorized users

Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP) levels >130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. β-blockers are playing an increasingly important role in the management of hypertension in high-risk patients. β-blockers are a heterogeneous class of agents, and this review presents the differences between β-blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by β-blockers are only effective if patients adhere to medication treatment long term. β-blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients

Highly electronegative metallic contacts to semiconductors using polymeric sulfur nitride

The Schottky barriers formed on n‐ZnS and n‐ZnSe by polymeric sulfur nitride have been compared to barriers formed by Au. Barrier energies as determined by photoresponse, current‐voltage, and capacitance‐voltage methods show that (SN)_x is approximately 1.0 eV higher than Au on n‐ZnS and 0.3–0.4 eV higher than Au on n‐ZnSe. We believe that this is the first report of any metallic contact more electronegative than Au

Electron tunneling time measured by photoluminescence excitation correlation spectroscopy

The tunneling time for electrons to escape from the lowest quasibound state in the quantum wells of GaAs/AlAs/GaAs/AlAs/GaAs double-barrier heterostructures with barriers between 16 and 62 Å has been measured at 80 K using photoluminescence excitation correlation spectroscopy. The decay time for samples with barrier thicknesses from 16 Å (≈12 ps) to 34 Å(≈800 ps) depends exponentially on barrier thickness, in good agreement with calculations of electron tunneling time derived from the energy width of the resonance. Electron and heavy hole carrier densities are observed to decay at the same rate, indicating a coupling between the two decay processes

Fractionation of soil and 15N nitrogen to separate the organic and clay interactions of immobilized N

Includes bibliographical references (pages 211-212).Labelled 15N was added to two soils in cylinders in the field, and allowed to equilibrate for two summers of crop growth. The labelled soils were fractionated to provide information on the effect of organic and inorganic colloids on the stabilization of immobilized, 15N. Organic materials removed by 0.5 N NaOH without pretreatment contained more 15N than those extracted by the same reagent following decalcification and removal of sesquioxides with dithionite and HCl. Both extracts had similar amino acid (contents) and similar degrees of hydrolability. A fractionation system using an initial 0.1 M NaOH–0.1 M Na4P2O7 extraction followed by sonication and peptization in H2O yielded a humic acid fraction and a sedimentation fraction (< 0.04 μm) which differed markedly in degree of hydrolyzability, 15N content and amino acid-N content. The N associated with inorganic colloids < 0.04 μm, and that remaining in solution after the removal of larger particles accounted for 50% of the amino acid-N in a clay soil, and 40% in a fine sandy loam soil. Removal of sesquioxides followed by a second 0.5 N NaOH extraction reduced the N content of the colloidal size fractions of both soils, indicating that amorphous iron and aluminum compounds on the surface of clays are probably the active agents in bonding organic N to inorganic colloids. It is suggested that the nonhydrolytic technique, based largely on dispersion of the inorganic–organic colloids and analyses of the sediment, could be used to interpret the fate of microbiologically immobilized N compounds in the soil. Materials removed by 0.1 M Na4P2O7 were associated with polyvalent cations in the soil. Materials such as cytoplasmic constituents, released from the biomass during ultrasonic vibration or as lytic products would be expected to be adsorbed to inorganic colloids. They should be concentrated in the < 0.04 μm-size fraction. Cell wall and other particulate debris with a faster setting velocity would be expected to appear in larger-sized sedimentation fractions

A review of UK media coverage of physical activity associated with the publication of special issues in a high-impact medical journal

Objectives: The media is a substantial vehicle for conveying public health messages to the public. This study examined the extent to which the publication of special issues in a high-impact medical journal in 2012 and 2016 generated media interest in physical activity and health in the UK and explored the main issues that were reported. Study design: This is a systematic narrative review of print media. Methods: Relevant print news articles were identified by searching Factiva and Google News. The timeframe of each search was 2 weeks, using the publication date of each special issue as the anchor point. Overall, 20 articles were included in the analysis for 2012 and 37 articles for 2016. Results: The news media coverage was encouraging for the profile of physical activity and health. In 2012 and 2016, common themes included the benefits of physical activity and the risks of being inactive, comparisons between mortality rates from physical inactivity and smoking and the recommended volume of physical activity to benefit health. Conclusions: The profile given to an issue through prestigious scientific publication is one of the levers for community attention and policy change. Efforts are needed to further use the media for improving policy, practice and public awareness, which are antecedents to population health change