1011-P: Therapeutic Potential of Novel Combination of a Long-Acting Glucagon Analog (HM15136) and Antidiabetic Drugs for the Treatment of Obesity

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1011-P
Author(s):  
YOUNG JIN PARK ◽  
JONG SUK LEE ◽  
JUNG KUK KIM ◽  
DAEJIN KIM ◽  
YOUNG HOON KIM ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Antidiabetic Drugs ◽  
Treatment Of Obesity ◽  
Long Acting

scholarly journals Pharmacotherapeutic strategy for COPD patients: focus on dual bronchodilators

2021 ◽  
pp. 38-44
Author(s):  
A. I. Sinopalnikov
Keyword(s):  
Therapeutic Potential ◽  
Evidence Base ◽  
Baseline Risk ◽  
Copd Patients ◽  
Muscarinic Receptor Antagonists ◽  
History Of ◽  
Inflammatory Profile ◽  
Long Acting ◽  
Systemic Antibiotics ◽  
Active Controls

For two decades, the GOLD Initiative has consistently identified the use of bronchodilators as a priority in the pharmacotherapeutic strategy for COPD. The authors of international and national clinical guidelines consider fixed combinations of long-acting beta2-agonists (LABAs) and long-acting muscarinic receptor antagonists (LAMAs) as “first-line” drugs in most patients with COPD. Numerous clinical studies have shown that fixed LABAs/LAMAs combinations provide optimal bronchodilation and play a paramount role in preventing exacerbations of COPD. Outperforming placebo and active controls, LABAs, LAMAs, inhaled glucocorticosteroids (ICS)/LABAs combination bronchodilators may differ in their therapeutic potential. The available evidence base currently does not allow to make an unambiguous choice in favor of one or another fixed LABAs/ LAMAs combination. With the appearance of “triple” combinations (ICS/LABAs/LAMAs) on the pharmaceutical market, the issue of their comparison with “dual” bronchodilators has become particularly acute. Currently available data suggest that the use of “triple” therapy is not considered as a starting treatment option for COPD and is appropriate only in a subgroup of patients with a higher baseline risk of exacerbations: in the presence of a history of exacerbations ≥ 1, which required prescription of systemic antibiotics and/or glucocorticosteroids, or necessitated hospitalization during the previous year. Thus, ICS-containing therapy is justified only in cases of recurrent exacerbations of moderate COPD or single episodes of severe exacerbations, despite the continued administration of LABAs/LAMAs, as well as in certain categories of patients whose inflammatory profile suggests a “response” to ICS.

Abstract 1382: AlbuBNP (Cardeva), a Novel Recombinant Human B-Type Natriuretic Peptide Serum Albumin Fusion Protein Has Prolonged Renal Enhancing Properties When Compared to Human BNP.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Horng H Chen ◽  
Fernando L Matrin ◽  
Alessandro Cataliotti ◽  
John A Schirger ◽  
John C Burnett
Keyword(s):  
Fusion Protein ◽  
Serum Albumin ◽  
Single Molecule ◽  
Therapeutic Potential ◽  
Renal Diseases ◽  
Elimination Half ◽  
Sustained Reduction ◽  
Anesthetized Dogs ◽  
Long Acting ◽  
Sustained Increase

BACKGROUND: AlbuBNP is a novel recombinant human BNP serum albumin fusion protein which possesses a significantly longer elimination half-life compared to BNP. To date, it remains unclear if this novel protein which represents a single molecule of BNP synthesized with the carrier protein albumin can enter the post glomerular/tubular system due to the fusion of BNP to albumin and mediate renal actions. We hypothesized that this fusion protein will have potent renal actions and possess prolonged renal hemodynamic enhancing and excretory properties based upon its unique structure as compared to native BNP. METHODS: We compared the cardiorenal and humoral actions of intravenous(IV) bolus of administration of AlbuBNP (Cardeva, CoGenesys, Rockville MD) (5 mg/kg, n=7) and Human BNP (Phoenix Pharmaceutical, Belmont CA) (25 μ g/Kg, n=5) in two groups of normal anesthetized dogs. * p<0.05 RESULTS: Single IV bolus of AlbuBNP resulted in a sustained increase in plasma cGMP (5±1 to 9±2 pmol/ml*) and urinary cGMP excretion (1136±113 to 2556±417 pmol/min*), markers of the biological activity of BNP, which remained elevated at the termination of the experiment at 270 minutes. In contrast, with human BNP, both plasma and urinary cGMP peaked at 30 minutes and returned to baseline by 150 minutes. In a similar fashion, there was a sustained increase in natriuresis (39±12 to 159±38 μEq/min*), diuresis (0.2±0.1 to 1.1±0.3 ml/min*), renal blood flow (220±22 to 301±33 ml/min*), and glomerular filtration rate (34±2 to 62±13 ml/min*) with AlbuBNP while with human BNP, these renal effects peaked at 30 minutes and returned to baseline by 150 minutes. Furthermore, there was a gradual and sustained suppression of plasma aldosterone (7.8±2 to 3.6±1 ng/dL*) with AlbuBNP. Likewise, there was a more sustained reduction of cardiac filling pressures with AlbuBNP as compared to human BNP. CONCLUSION: We report for the first time that this newly developed BNP/albumin fusion protein has a more prolonged and sustained renal enhancing properties compared to human BNP. Thus, AlbuBNP (Cardeva) represents a novel long-acting renal enhancing and aldosterone suppressing drug which has therapeutic potential for the management of cardiovascular and renal diseases that should be defined in further studies.

OXM-104, a potential candidate for the treatment of obesity, NASH and type 2 diabetes

2021 ◽  
Author(s):  
Ashref Kayed ◽  
Simone Melander ◽  
Kim Andreassen ◽  
Morten Karsdal ◽  
Kim Henriksen
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Agonist ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Potential Candidate ◽  
Alcoholic Fatty Liver ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
Long Acting

Abstract Obesity-related metabolic disorders, including non-alcoholic fatty liver disease and its more progressive form non-alcoholic steatohepatitis, are causing an increased health burden, especially due to the lack of approved treatment options. Using preclinical models of NASH, obesity, and type 2 diabetes, we investigated the effects of a long-acting glucagon-like peptide-1(GLP-1) and glucagon (GCG) receptor agonist OXM-104 head to head with once-daily GLP-1/GCG receptor agonist cotadutide and once-weekly GLP-1 receptor agonist semaglutide. OXM-104, cotadutide, and semaglutide elicited marked reductions in body weight and improved glucose control. In contrast, hepatoprotective effects, i.e., reductions in steatosis and fibrosis, as well as liver fibrosis biomarkers, were more prominent with OXM-104 and cotadutide than effects seen with semaglutide. This is demonstrated by improved NAFLD activity score (NAS) by OXM-104 and cotadutide which underlines the importance of the GCG receptor. Thus, these results underline the potential of OXM-104 as a promising therapeutic option for the resolution of NASH, but also as a therapeutic option for type 2 diabetes and obesity.

scholarly journals Studies on Analysis of Antioxidant and Enzyme Inhibitory Activity of Vitex negundo Linn.

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Ved Prakash ◽  
Shelly Rana ◽  
Anand Sagar
Keyword(s):  
Urease Activity ◽  
Therapeutic Potential ◽  
Radical Scavenging Activity ◽  
Scientific Evidence ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Vitex Negundo ◽  
Leaf Extracts ◽  
Treatment Of Obesity ◽  
Dpph Radical Scavenging

The current study was designed to investigate the leaf extracts of Vitex negundo Linn. for their antioxidant and enzyme inhibitory (α-amylae and urease) activity. The antioxidant capacity of the different extracts (methanol, acetone and aqueous) of this plant was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) and reducing power tests. The plant exhibited good DPPH radical scavenging activity and moderate reducing power potential Further, all the extracts of V. negundo were reported to possess good anti-alpha amylase and anti-urease activity of greater than 50% in all the solvents used at a concentration of 1 mg/mL. Thus the study provided scientific evidence to the traditional uses of this plant in the treatment of obesity, diabetes, ulcers, kidney stones etc. Therefore, the leaf extracts of this plant can be selected for further investigation to determine their therapeutic potential.

scholarly journals Elaiophylin reduces body weight and lowers glucose levels in obese mice by activating AMPK

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruoxuan Bao ◽  
Yongmei Meng ◽  
Haibo Zhang ◽  
Chen Yang ◽  
Wei Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Chronic Diseases ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Pharmacological Intervention ◽  
Obese Mouse ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Treatment Of Obesity

AbstractObesity is an epidemic affecting 13% of the global population and increasing the risk of many chronic diseases. However, only several drugs are licensed for pharmacological intervention for the treatment of obesity. As a master regulator of metabolism, the therapeutic potential of AMPK is widely recognized and aggressively pursued for the treatment of metabolic diseases. We found that elaiophylin (Ela) rapidly activates AMPK in a panel of cancer-cell lines, as well as primary hepatocytes and adipocytes. Meanwhile, Ela inhibits the mTORC1 complex, turning on catabolism and turning off anabolism together with AMPK. In vitro and in vivo studies showed that Ela does not activate AMPK directly, instead, it increases cellular AMP/ATP and ADP/ATP ratios, leading to AMPK phosphorylation in a LKB1-dependent manner. AMPK activation induced by Ela caused changes in diverse metabolic genes, thereby promoting glucose consumption and fatty acid oxidation. Importantly, Ela activates AMPK in mouse liver and adipose tissue. As a consequence, it reduces body weight and blood glucose levels and improves glucose and insulin tolerance in both ob/ob and high-fat diet-induced obese mouse models. Our study has identified a novel AMPK activator as a candidate drug for the treatment of obesity and its associated chronic diseases.

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