The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have ...not been described.
To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control.
Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020; follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin.
Patients were randomized in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks. Tirzepatide was initiated at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved.
The primary end point was mean change from baseline in glycated hemoglobin A1c (HbA1c) at week 40. The 5 key secondary end points included mean change in body weight and percentage of patients achieving prespecified HbA1c levels.
Among 475 randomized participants (211 44% women; mean SD age, 60.6 9.9 years; mean SD HbA1c, 8.31% 0.85%), 451 (94.9%) completed the trial. Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group. At week 40, mean HbA1c change from baseline was -2.40% with 10-mg tirzepatide and -2.34% with 15-mg tirzepatide vs -0.86% with placebo (10 mg: difference vs placebo, -1.53% 97.5% CI, -1.80% to -1.27%; 15 mg: difference vs placebo, -1.47% 97.5% CI, -1.75% to -1.20%; P < .001 for both). Mean HbA1c change from baseline was -2.11% with 5-mg tirzepatide (difference vs placebo, -1.24% 95% CI, -1.48% to -1.01%; P < .001). Mean body weight change from baseline was -5.4 kg with 5-mg tirzepatide, -7.5 kg with 10-mg tirzepatide, -8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo (5 mg: difference, -7.1 kg 95% CI, -8.7 to -5.4; 10 mg: difference, -9.1 kg 95% CI, -10.7 to -7.5; 15 mg: difference, -10.5 kg 95% CI, -12.1 to -8.8; P < .001 for all). Higher percentages of patients treated with tirzepatide vs those treated with placebo had HbA1c less than 7% (85%-90% vs 34%; P < .001 for all). The most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%).
Among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine, the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks.
ClinicalTrials.gov Identifier: NCT04039503.
This paper reviews the data available in the bibliography relative to most important economical factors in an offshore wind farm, including the acquisition/installation of wind turbines and ...foundations, electrical infrastructure, design and project management, and operation/maintenance. These data are necessary to carry out any profitability analysis, or optimization procedure. In order to establish a common reference, prices have been translated into a unique currency and taken to the present year. Taking into account these considerations, the paper presents an estimation of the different costs as a function of the farm size. Finally, the main cost drivers affecting the capital and operating expenditures are presented and discussed.
•This is the first paper in a journal summarizing the costs in offshore wind farms.•A table with different inter-array cables, including electrical characteristics, is also included for the first time in a paper with an overall review of costs.•The big disparity in prices is discussed, and when possible, a relationship between the corresponding cost and the wind farm capacity is provided.•In the presented paper, the sources are exactly identified, including pages where data were found and the price in the original currency.
Carbon capture and storage (CCS) is an essential technology to mitigate global CO2 emissions from power and industry sectors. Despite the increasing recognition of its importance to achieve the ...net-zero target, current CCS deployment is far behind targeted ambitions. A key reason is that CCS is often perceived as too expensive. The costs of CCS have however traditionally been looked at from the industrial plant perspective, which does not necessarily reflect the end user’s one. This paper addresses the incomplete view by investigating the impact of implementing CCS in industrial facilities on the overall costs and CO2 emissions of end-user products and services. As an example, we examine the extent to which an increase in costs of raw materials (cement and steel) due to CCS impacts the costs of building a bridge. Results show that although CCS significantly increases cement and steel costs, the subsequent increment in the overall bridge construction cost remains marginal (∼1%). This 1% cost increase, however, enables a deep reduction in CO2 emissions (∼51%) associated with the bridge construction. Although more research is needed in this area, this work is the first step to a better understanding of the real cost and benefits of CCS.
Since de Gennes coined in 1992 the term Janus particle (JP), there has been a continued effort to develop this field. The purpose of this review is to present the most relevant theoretical and ...experimental results obtained so far on the surface activity of amphiphilic JPs at fluid interfaces. The surface activity of JPs at fluid–fluid interfaces can be experimentally determined using two different methods: the classical Langmuir balance or the pendant drop tensiometry. The second method requires much less amount of sample than the first one, but it has also some experimental limitations. In all cases collected here the JPs exhibited a higher surface or interfacial activity than the corresponding homogeneous particles. This reveals the significant advantage of JPs for the stabilization of emulsions and foams.
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•Janus particles exhibit surface activity at fluid–fluid interfaces.•Physical properties of Janus particle-laden interfaces are studied.•Shape and wettability of Janus particles affect their arrangement at fluid–fluid interfaces.•Surface activity of Janus particles is explored using pendant drop tensiometry.
Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist under development for the treatment of type 2 diabetes. The aim of this ...substudy was to characterise the changes in liver fat content (LFC), volume of visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT) in response to tirzepatide or insulin degludec in a subpopulation of the SURPASS-3 study.
This substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial was done at 45 medical research centres and hospitals across eight countries (Argentina, Austria, Greece, Hungary, Italy, Romania, Spain, and the USA). Eligible participants were adults with type 2 diabetes, a baseline HbA
7·0-10·5% (53-91 mmol/mol), a BMI of at least 25 kg/m
, stable weight, were insulin-naive, and on treatment with metformin alone or in combination with a SGLT2 inhibitor for at least 3 months before screening. In addition to the main study inclusion criteria, substudy participants had a fatty liver index of at least 60. Participants had an MRI scan and were randomised (1:1:1:1) in the main study to subcutaneous injection once per week of tirzepatide 5 mg, 10 mg, or 15 mg, or subcutaneous injection once per day of titrated insulin degludec, using an interactive web-response system, and were stratified by country, HbA
, and concomitant oral anti-hyperglycaemic medication. The primary efficacy endpoint was the change from baseline in LFC (as measured by MRI-proton density fat fraction MRI-PDFF) at week 52 using pooled data from the tirzepatide 10 mg and 15 mg groups versus insulin degludec. Analyses were assessed in the enrolled MRI population, which consisted of participants in the modified intention-to-treat population of the main study who also had a valid MRI at either baseline or after baseline. This is a substudy of the trial registered with ClinicalTrials.gov, number NCT03882970, and is complete.
From April 1, 2019, to Nov 15, 2019, 502 participants were assessed for eligibility to participate in this substudy, 296 (59%) of whom were included in the enrolled MRI population and randomly assigned to treatment (tirzepatide 5 mg, n=71; tirzepatide 10 mg, n=79; tirzepatide 15 mg, n=72; and insulin degludec, n=74). Baseline demographics and clinical characteristics were similar across all treatment groups. From an overall mean baseline LFC of 15·71% (SD 8·93), the absolute reduction in LFC at week 52 was significantly greater for the pooled tirzepatide 10 mg and 15 mg groups (-8·09%, SE 0·57) versus the insulin degludec group (-3·38%, 0·83). The estimated treatment difference versus insulin degludec was -4·71% (95% CI -6·72 to -2·70; p<0·0001). The reduction in LFC was significantly correlated (p≤0·0006) with baseline LFC (ρ=-0·71), reductions in VAT (ρ=0·29), reductions in ASAT (ρ=0·33), and reductions in body weight (ρ=0·34) in the tirzepatide groups.
Tirzepatide showed a significant reduction in LFC and VAT and ASAT volumes compared with insulin degludec in this subpopulation of patients with type 2 diabetes in the SURPASS-3 study. These data provide additional evidence on the metabolic effects of this novel dual GIP and GLP-1 receptor agonist.
Eli Lilly and Company.
The increasing environmental pollution with particular reference to emerging contaminants, toxic heavy elements, and other hazardous agents is a serious concern worldwide. Considering this global ...issue, there is an urgent need to design and develop strategic measuring techniques with higher efficacy and precision to detect a broader spectrum of numerous contaminants. The development of precise instruments can further help in real-time and in-process monitoring of the generation and release of environmental pollutants from different industrial sectors. Moreover, real-time monitoring can also reduce the excessive consumption of several harsh chemicals and reagents with an added advantage of on-site determination of contaminant composition prior to discharge into the environment. With key scientific advances, electrochemical biosensors have gained considerable attention to solve this problem. Electrochemical biosensors can be an excellent fit as an analytical tool for monitoring programs to implement legislation. Herein, we reviewed the current trends in the use of electrochemical biosensors as novel tools to detect various contaminant types including toxic heavy elements. A particular emphasis was given to screen-printed electrodes, nanowire sensors, and paper-based biosensors and their role in the pollution detection processes. Towards the end, the work is wrapped up with concluding remarks and future perspectives. In summary, electrochemical biosensors and related areas such as bioelectronics, and (bio)-nanotechnology seem to be growing areas that will have a marked influence on the development of new bio-sensing strategies in future studies.
In recent years, ever-increasing scientific knowledge and modern high-tech advancements in micro- and nano-scales fabrication technologies have impacted significantly on various scientific fields. A ...micro-level approach so-called "microfluidic technology" has rapidly evolved as a powerful tool for numerous applications with special reference to bioengineering and biomedical engineering research. Therefore, a transformative effect has been felt, for instance, in biological sample handling, analyte sensing cell-based assay, tissue engineering, molecular diagnostics, and drug screening, etc. Besides such huge multi-functional potentialities, microfluidic technology also offers the opportunity to mimic different organs to address the complexity of animal-based testing models effectively. The combination of fluid physics along with three-dimensional (3-D) cell compartmentalization has sustained popularity as organ-on-a-chip. In this context, simple humanoid model systems which are important for a wide range of research fields rely on the development of a microfluidic system. The basic idea is to provide an artificial testing subject that resembles the human body in every aspect. For instance, drug testing in the pharma industry is crucial to assure proper function. Development of microfluidic-based technology bridges the gap between in vitro and in vivo models offering new approaches to research in medicine, biology, and pharmacology, among others. This is also because microfluidic-based 3-D niche has enormous potential to accommodate cells/tissues to create a physiologically relevant environment, thus, bridge/fill in the gap between extensively studied animal models and human-based clinical trials. This review highlights principles, fabrication techniques, and recent progress of organs-on-chip research. Herein, we also point out some opportunities for microfluidic technology in the future research which is still infancy to accurately design, address and mimic the in vivo niche.
•Bio-based materials including PHAs, alginate, and chitin are reviewed.•Biotechnological advancements from a biomaterials perspective are discussed.•Tissue engineering and regenerative medicine ...potential are reviewed.
Recently, a wider spectrum of bio-based materials and materials-based novel constructs and systems has been engineered with high interests. The key objective is to help for an enhanced/better quality of life in a secure way by avoiding/limiting various adverse effects of some in practice traditional therapies. In this context, different methodological approaches including in vitro, in vivo, and ex vivo techniques have been exploited, so far. Among them, bio-based therapeutic constructs are of supreme interests for an enhanced and efficient delivery in the current biomedical sector of the modern world. The development of new types of novel, effective and highly reliable materials-based novel constructs for multipurpose applications is essential and a core demand to tackle many human health related diseases. Bio-based materials possess several complementary functionalities, e.g. unique chemical structure, bioactivity, non-toxicity, biocompatibility, biodegradability, recyclability, etc. that position them well in the modern world's materials sector. In this context, the utilization of biomaterials provides extensive opportunities for experimentation in the field of interdisciplinary and multidisciplinary scientific research. With an aim to address the global dependence on petroleum-based polymers, researchers have been redirecting their interests to the engineering of biological materials for targeted applications in different industries including cosmetics, pharmaceuticals, and other biotechnological or biomedical applications. Herein, we reviewed biotechnological advancements at large and tissue engineering from a biomaterials perspective in particular and envision directions of future developments.
Let A be a complete normed complex algebra, let π:A→A be a nonzero contractive linear projection, and consider π(A) as a complete normed complex algebra under the product (x,y)→π(xy). We prove the ...following results.-If A is unital and associative (respectively, alternative) and satisfies the von Neumann inequality, and if π satisfies the weak conditional expectation property(WCE)π(π(a)π(b))=π(π(a)b)=π(aπ(b)) for alla,b∈A, then π(A) is unital and associative (respectively, alternative) and satisfies the von Neumann inequality.-If A is an Arazy algebra, and if π satisfies the weak Jordan conditional expectation (namely the symmetrization of (WCE)), then π(A) is an Arazy algebra. (We note that, in the possibly non power-associative setting, Arazy algebras are the adequate substitutes of complete normed unital power-associative complex algebras satisfying the von Neumann inequality.)-If the closed multiplication algebra of A satisfies the von Neumann inequality, and if π is an elementary operator, then the closed multiplication algebra of π(A) satisfies the von Neumann inequality.
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