Once-Weekly Semaglutide in Adults with Overweight or Obesity Wilding, John P H; Batterham, Rachel L; Calanna, Salvatore ...
New England journal of medicine/The New England journal of medicine,
03/2021, Letnik:
384, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle ...intervention has not been confirmed.
In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.
The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval CI, -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants 86.4% vs. 182 31.5%), 10% or more (838 69.1% vs. 69 12.0%), and 15% or more (612 50.5% vs. 28 4.9%) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 4.5% vs. 5 0.8%).
In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
Nanoconjugations have been demonstrated to be a dominant strategy for drug delivery and biomedical applications. In this review, we intend to describe several strategies for drug formulation, ...especially to improve the bioavailability of poorly water-soluble molecules for future application in the therapy of numerous diseases. The context of current studies will give readers an overview of the conjugation strategies for fabricating nanoparticles, which have expanded from conjugated materials to the surface conjugation of nanovehicles. Moreover, nanoconjugates for theranostics are also discussed and highlighted. Overall, these state-of-the-art conjugation methods and these techniques and applications for nanoparticulate systems of poorly water-soluble drugs will inspire scientists to explore and discover more productive techniques and methodologies for drug development.
Targeted exosomal delivery systems for precision nanomedicine attract wide interest across areas of molecular cell biology, pharmaceutical sciences, and nanoengineering. Exosomes are naturally ...derived 50–150 nm nanovesicles that play important roles in cell‐to‐cell and/or cell‐to‐tissue communications and cross‐species communication. Exosomes are also a promising class of novel drug delivery vehicles owing to their ability to shield their payload from chemical and enzymatic degradations as well as to evade recognition by and subsequent removal by the immune system. Combined with a new class of affinity ligands known as aptamers or chemical antibodies, molecularly targeted exosomes are poised to become the next generation of smartly engineered nanovesicles for precision medicine. Here, recent advances in targeted exosomal delivery systems engineered by aptamer for future strategies to promote human health using this class of human‐derived nanovesicles are summarized.
Recent advances in research and development of aptamer‐guided exosomes as a new nanoengineering strategy to achieve targeted drug delivery using bio‐nanoparticles highlight a promising next generation of targeted drug delivery systems. Cross‐fertilization between areas of exosomes and aptamers in both preclinical translational studies predicts a bright future for aptamer‐guided exosomal delivery in precision nanomedicine.
Despite many available approaches for transdermal drug delivery, patient compliance and drug targeting at the desired concentration are still concerns for effective therapies. Precise and efficient ...film-forming systems provide great potential for controlling drug delivery through the skin with the combined advantages of films and hydrogels. The associated disadvantages of both systems (films and hydrogels) will be overcome in film-forming systems. Different strategies have been designed to control drug release through the skin, including changes to film-forming polymers, plasticizers, additives or even model drugs in formulations. In the current review, we aim to discuss the recent advances in film-forming systems to provide the principles and review the methods of these systems as applied to controlled drug release. Advances in the design of film-forming systems open a new generation of these systems.
Although zein is a natural protein derived from corn, it has attracted much interest in pharmaceutical and biomedical sciences. Recent remarkable investigations on the use of zein in controlled drug ...delivery have contributed both important knowledge and potential applications of various products, particularly in the delivery of poorly water-soluble drugs. Zein has also been approved by the Food and Drug Administration for oral delivery. Substantial research has been performed to demonstrate the roles and promise of materials containing zein for pharmaceutical applications. Significant efforts have focused on the biodegradable and hydrophobic properties of zein and on technology using zein as a nanocarrier specifically for nanomedicine. However, important issues concerning the use of zein in technical advances and in the development of poorly water-soluble drugs must be addressed in order to use zein in translational research. This review aims to focus on the classification of potential approaches for using zein in the controlled release of poorly water-soluble drugs and to discuss recommended techniques for creating high-quality products from zein.
To evaluate improvement in survival of lymphoma patients from 1990 to 2014, stratified by age, sex and race using Surveillance Epidemiology and End-Result Survey Program (SEER) data.
We identified ...113,788 incident lymphoma cases from nine SEER cancer registries were followed up for cause-specific mortality from lymphoma. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and their respective 95% confidence interval (CIs) for various time periods within groups stratified by race, age and sex.
Five-year survival for Hodgkin's lymphoma (HL) was 89% for patients 20-49 years of age. For this age group, compared to 1990-1994, survival significantly improved in 2000-2004 (HR = 0.65; 95% CI: 0.54-0.78), 2005-2009 (HR = 0.46, 95% CI: 0.38-0.57) and 2010-2014 (HR = 0.29, 95% CI: 0.20-0.41). Hodgkin's lymphoma patients aged 75-85 years had 5-year survival of 37% and in these patients, compared to 1990-1994, survival only improved from 2005 onward (HR = 0.67, 95% CI: 0.50-0.90). In patients with non-Hodgkin's Lymphoma (NHL), all age groups showed survival improvements between 1990-1994 period and 2010-2014 period. Improvements in HL and NHL survival were seen for all race categories and both genders.
Survival among US lymphoma patients has improved substantially between 1990-1994 period and 2010-2014 period, though disease-specific mortality was still higher in older age groups.
Display omitted
Although solid dispersions have been reported as an efficient drug delivery system, the design of specific dosage forms for pharmaceutical therapy is necessary to improve the ...solubility and bioavailability of poorly water-soluble drugs. Solid dispersions can be incorporated in general solid dosage forms such as powders, granules, capsules and tablets, but only to enhance solubility and the dissolution rate. However, further development of solid dispersions will be required in certain circumstances for further in vivo drug improvement of those solid dosage forms. In the current review, specific designs of solid dosage forms for controlled drug release will be reported. Moreover, methods and strategies for incorporating these solid dispersions into controlled drug release forms will also be discussed. Overall, the outlook of current studies will provide potential approaches for the further improvement of solid dispersions, especially for clinical developments in pharmaceutical therapy.
The improvement of mucoadhesive buccal formulations has attracted profound interest in recent years. Drug permeability and controlled drug release via this route of administration are still a concern ...for effective therapy, although various strategies have been proposed. Advanced developments in nanotechnology have been investigated with promising clinical applications. The incorporation of nanoparticles in dosage forms for buccal delivery not only ensures efficient delivery but also reduces side effects to biological systems. Many approaches have been suggested to load and deliver nanoparticles containing drugs to the buccal mucosa both in topical and systemic administrations. This paper describes recent advanced concepts to include nanoparticles in dosage forms with improving drug delivery or targeting. The classification and discussion of these technologies are aimed at providing an overview of current strategies for applying controlled drug delivery. All remarkable findings will encourage innovative nanoparticle-delivered dosage forms for buccal delivery in clinical applications.
Display omitted
Ternary solid dispersions have been demonstrated to be an effective strategy in the improvement of drug absorption and bioavailability.
The applications of the combination of hydrophilic polymers ...with the potential of hydrophobic polymer incorporation at moderate concentrations have been discussed in recent publications.
In this paper, the general review of this specific type of solid dispersion will be provided with comprehensive understanding of polymer blends of either hydrophilic or hydrophobic polymers. A detailed description of miscible polymers has been developed in recent studies. In addition to dissolution rate improvement, the role of second polymers in crystal growth inhibition and in maintaining the amorphous state will be mentioned.
We also present a summary of characterization techniques commonly used to evaluate solid dispersion and polymer miscibility.
Display omitted
The long history of discovery and recently encouraging studies of the anti-cancer effect of aspirin promise a closer step to widely used aspirin-based medication in cancer therapy. To ...resolve the poor water-solubility of aspirin and low encapsulation efficiency of exosomes for further developing a new delivery of aspirin as anti-cancer treatment, our nanoamorphous exosomal delivery platform was established. In this study, the anti-tumour effects of nanoamorphous aspirin-loaded exosomes with exosomes derived from breast and colorectal cancer cells, were comprehensively studied using both in vitro and in vivo models. These exosomes displayed enhanced cellular uptake via both clathrin-dependent and -independent endocytosis pathways, and significantly improved cytotoxicity of aspirin to breast and colorectal cancer cells, accompanied by the enhanced apoptosis and autophagy. Remarkably, this nanoamorphous exosomal platform endowed aspirin with the unprecedented cancer stem cell eradication capacity. Further animal study demonstrated that this developed exosomal system was able to efficiently deliver aspirin to in vivo tumours. The active targeting of these exosomes to tumour was further improved by conjugating an aptamer specifically targeting EpCAM protein. Hence, this nanoamorphous structured exosome system effectively transformed aspirin into a potential cancer stem cell killer with distinguished properties for clinical translation.
PDF
