The Discovery and Development of Liraglutide and Semaglutide

We describe one such approach, albumin binding, and explain how it was applied in the development of the human GLP-1 analog liraglutide once daily and, subsequently, semaglutide once weekly. The pharmacology of these two long-acting GLP-1 analogs, in terms of improving glycemic control, reducing body weight and decreasing cardiovascular (CV) risk, is also reviewed, together with some novel biology. In addition, we describe the importance of accurate target (GLP-1 receptor) tissue expression analysis. Now an established class of agents, GLP-1-based therapies represent a significant advance in the treatment of T2D. All currently available GLP-1 receptor agonists (GLP-1RAs) are, however, injectable. Ongoing efforts to advance this class of agents include, therefore, attempts to develop an oral formulation. In the final section of this article, we describe an oral formulation of semaglutide that is currently in phase 3 clinical development for the treatment of T2D, as well as summarizing other therapeutic applications—beyond T2D—of liraglutide and semaglutide. Albumin Binding as a Concept for Creating Long-Acting GLP-1 Analogs Human serum albumin (HSA) is among the most stable and abundant of plasma proteins. It comprises three homologous domains assembled into a heart-shaped protein. Approximately 10–15 g is produced by the liver daily, which—owing to its long half-life of several weeks—results in an HSA plasma concentration of 35–50 g/L (~...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research

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Publication date: Available online 25 May 2019Source: Preventive Veterinary MedicineAuthor(s): Ricardo Lopes, Amanda Brinch Kruse, Liza Rosenbaum Nielsen, Telmo Pina Nunes, Lis AlbanAbstractIn modern livestock farming, there is an increasing understanding that antimicrobial (AM) consumption must be kept low – preferably without compromising animal welfare or productivity. This requires an understanding of the relationship between AM use, productivity, biosecurity, vaccination and herd demographics. To obtain this, we undertook an Additive Bayesian Network analysis using data from 2014-15, covering 157 Danish sow herd...
Source: Preventive Veterinary Medicine - Category: Veterinary Research Source Type: research
Publication date: Available online 25 May 2019Source: Journal of Physics and Chemistry of SolidsAuthor(s): D. Alburquenque, L. Troncoso, J.C. Denardin, J.F. Marco, J.L. GautierAbstractManganese nickel oxides with a spinel-related structure, NixMn3-xO4-δ (x = 0.5 or 0.75), were synthesized by an ultrasound-assisted sol-gel method. Inductively coupled plasma atomic optical emission spectroscopy and energy-dispersive X-ray spectroscopy analysis showed good agreement with the nominal oxide compositions. The Rietveld refinement of the X-ray data indicated that both Ni0.5Mn2.5O4-δ and Ni0.75Mn2.25O4-δ cryst...
Source: Journal of Physics and Chemistry of Solids - Category: Physics Source Type: research
In conclusion, the results suggested that SAB could attenuate HUVEC cells damage treated with HG or PA via Sirt1 and might be a potential therapy agent for the diabetic cardiopathy treatment. PMID: 31118974 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Authors: Shi L, Feng L, Zhang M, Li X, Yang Y, Zhang Y, Ni Q Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Many trials have shown that Abelmoschus manihot could further improve proteinuria and protect kidney function in patients with DN when added to a renin-angiotensin system (RAS) blocker. A systematic assessment of the efficacy and safety of A. manihot in DN is essential. Eight electronic databases were searched to identify eligible trials published from inception to December 2017. The Cochrane Risk of Bias Tool was used to evaluate the methodological quality of eligi...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
In conclusion, the compound has a protective effect against ALF in rats, and an underlying mechanism is involved in the TGF-β1/Smad signaling pathway. PMID: 31118972 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Conclusions: AD is a complex disease caused by multiple factors. Shen Zhi Ling oral liquid exhibited multiple and multitarget effects and great potential for treating AD. The continuous development of molecular biology and related disciplines will further elucidate the mechanism of Shen Zhi Ling oral liquid intervention in AD. PMID: 31118971 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Authors: Zhu J, Xing G, Shen T, Xu G, Peng Y, Rao J, Shi R Abstract Backgrounds: Prediabetes is a condition in which a person's blood glucose levels are higher than normal physiological levels but lower compared to patients with diabetes. Up to 70% of individuals with prediabetes will eventually develop diabetes. To date, there have been no pharmaceutical drugs to treat diabetes. It is believed that early diagnosis and nonpharmacological intervention for prediabetes are critical for effective prevention of diabetes. Most individuals with prediabetes remain undiagnosed even after being evaluated using the standard t...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Authors: Vigna L, Morelli F, Agnelli GM, Napolitano F, Ratto D, Occhinegro A, Di Iorio C, Savino E, Girometta C, Brandalise F, Rossi P Abstract Epidemiological data indicate that subjects affected by obesity have an increased risk of developing mood disorders. The relationship between obesity and mood disorders is bidirectional. We assessed whether a Hericium erinaceus treatment improved depression, anxiety, sleep, and binge eating disorders after 8 weeks of supplementation in subjects affected by overweight or obesity under a low calorie diet regimen. Looking for a possible clinical biomarker, we assessed the seru...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Conclusion: This review contains information on medicinal plants used to manage diabetes mellitus, including their pharmacological properties and mechanisms of action as well as models used to investigate them. It also provides gaps that can form the basis for further investigations and development into useful medications for effective treatment of diabetes mellitus. PMID: 31118963 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Authors: Zhou YX, Zhang RQ, Rahman K, Cao ZX, Zhang H, Peng C Abstract Geniposide is a well-known iridoid glycoside compound and is an essential component of a wide variety of traditional phytomedicines, for example, Gardenia jasminoides Elli (Zhizi in Chinese), Eucommia ulmoides Oliv. (Duzhong in Chinese), Rehmannia glutinosa Libosch. (Dihuang in Chinese), and Achyranthes bidentata Bl. (Niuxi in Chinese). It is also the main bioactive component of Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides Ellis. Increasing pharmacological evidence supports multiple medicinal properties of geniposide including...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
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