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Jun Zhang, Xue-Jiao Wang, Xin Liu, Yi Huan, Miao-Miao Yang, Zhu-Fang Shen, Wen-Qing Jia, Zhi Jing, Shu-Qing Wang, Wei-Ren Xu, Xian-Chao Cheng, Run-Ling Wang
Peroxisome proliferators-activated receptors (PPARα, γ and δ) are potentially effective targets for Type 2 diabetes mellitus therapy. The severe effects of known glitazones and the successfully approved agents (saroglitazar and lobeglitazone) motivated us to study novelly potent PPARs drugs with improved safety profile. In this work, we received 15 carboxylic acids based on the combination principle to integrate the polar head of bezafibrate with the hydrophobic tail of pioglitazone. Another 12 tetrazoles based on the bioisosterism principle were obtained accordingly...
March 28, 2017: Oncotarget
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
Bipin Kumar Sethi, V Sri Nagesh, Jayant Kelwade, Ayesha Vaseem
No abstract text is available yet for this article.
December 2015: Journal of the Association of Physicians of India
Yaron Rotman, Arun J Sanyal
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress...
January 2017: Gut
Ashok Ghoghari, Ranjeet Dash, Chandrakant Bhatt, Kanchan Singh, Anil Jha, Harilal Patel, Rahul Gupta, Kevinkumar Kansagra, Nuggehally R Srinivas
A sensitive LC-MS/MS method was developed and validated for quantitation of saroglitazar using turboion spray interface with positive ion mode. A liquid-liquid extraction, with a mixture of dichloromethane and diethyl ether, was employed for the extraction of saroglitazar and glimepiride (IS) from human plasma. The chromatographic separation was achieved using an ACE-5, C18 (4.6 × 100 mm) column with a gradient mobile phase comprising acetonitrile and ammonium acetate buffer with trifluoracetic acid in purified water...
December 2016: Biomedical Chromatography: BMC
Arijit Ghosh, Pranab Kumar Sahana, Chanchal Das, Ananya Mandal, Nilanjan Sengupta
INTRODUCTION: Diabetic dyslipidaemia poses a therapeutic challenge. New therapies have emerged in this patient subgroup to enhance outcome and improve compliance. AIM: The aim of this study was to compare the effectiveness and safety of add on therapy of saroglitazar and fenofibrate with metformin in Indian patients with diabetic dyslipidaemia. MATERIALS AND METHODS: Adults patients with diabetic dyslipidaemia fulfilling the inclusion criteria were randomized in two groups...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
Alka Deshpande, Harsh Toshniwal, Shashank Joshi, Rajendrakumar H Jani
OBJECTIVE: This study was designed to explore the efficacy and safety of saroglitazar 4 mg on hypertriglyceridemia in patients with HIV associated lipodystrophy. METHODS: During this 12-week prospective, multi-centric, open-label, single arm exploratory study, 50 patients were enrolled to receive saroglitazar 4 mg orally once daily in the morning before breakfast. The primary efficacy endpoint was the percent change in triglyceride (TG) levels from baseline to Week 6 and Week 12...
2016: PloS One
Mukul R Jain, Suresh R Giri, Chitrang Trivedi, Bibhuti Bhoi, Akshyaya Rath, Geeta Vanage, Purvi Vyas, Ramchandra Ranvir, Pankaj R Patel
Saroglitazar is a novel nonthiazolidinediones (TZD) and nonfibric acid derivative designed to act as dual regulator of lipids and glucose metabolism by activating peroxisome proliferator-activated receptors (PPAR). These studies evaluate the efficacy and safety profile of Saroglitazar in preclinical in vitro and in vivo models. The EC50 values of Saroglitazar assessed in HepG2 cells using PPAR transactivation assay for hPPARα and hPPARγ were 0.65 pmol/L and 3 nmol/L, respectively. In db/db mice, 12-day treatment with Saroglitazar (0...
June 2015: Pharmacology Research & Perspectives
Aravind Sosale, Banshi Saboo, Bhavana Sosale
Diabetes mellitus (DM) is one of the most dreaded metabolic disorders in the world today. It is the leading cause of morbidity and mortality, and plays a cardinal role in quality of life and health economics. DM is associated with a high prevalence of microvascular and macrovascular complications. DM is a very important cardiovascular (CV) risk factor. Cardiovascular disease (CVD) has been implicated as the prime cause of mortality and morbidity in patients with DM. Hence, treatment of DM goes beyond glycemic control, and demands a multidisciplinary approach that comprehensively targets risk factors inherent in CV events...
2015: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Sadanand R Shetty, Soumitra Kumar, R P Mathur, Kamal H Sharma, Ashok D Jaiswal
UNLABELLED: Saroglitazar is a dual PPAR α/γ agonist approved in India for the management of diabetic dyslipidemia. AIMS: The objective of this study was to evaluate the safety and efficacy of saroglitazar 4 mg once daily in clinical practice. METHODS: This was an observational, multicenter, single-arm study. Patients with type 2 diabetes (with on-going antidiabetic medication), age above 18 years, and triglycerides ≥200 mg/dL were included...
January 2015: Indian Heart Journal
Sivasubramanian Ramakrishnan
No abstract text is available yet for this article.
January 2015: Indian Heart Journal
Shashank R Joshi
INTRODUCTION: Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects...
March 2015: Expert Opinion on Pharmacotherapy
Sanjay Chatterjee, Anirban Majumder, Subir Ray
Cardiovascular risk reduction is an important issue in the management of patients with Type 2 diabetes mellitus. Peroxisome proliferator activated receptor (PPAR) agonists favourably influence glycaemic and lipid parameters in patients with Type 2 diabetes and a dual PPAR agonist is expected to have favourable effect on both parameters. In this study we have analyzed the effect of Saroglitazar, a novel dual PPAR alpha &gamma agonist, on glycaemic and lipid parameters in Indian patients with Type 2 diabetes...
2015: Scientific Reports
Srinivasa P Munigoti, C V Harinarayan
A triad of high triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated small dense low-density lipoprotein particles occurring in a patient with type 2 diabetes is referred to atherogenic diabetic dyslipidemia (ADD). Despite statin therapy, a significant residual risk remains potentially attributable to increased triglyceride concentration and low HDL cholesterol, a characteristic hallmark of ADD. Current therapeutic options in reducing this residual risk include nicotinic acid, omega 3 fatty acids, and selective peroxisome proliferator-activated receptor-alpha (PPAR) agonists (fibrates)...
May 2014: Indian Journal of Endocrinology and Metabolism
Vikas Pai, A Paneerselvam, Satinath Mukhopadhyay, Anil Bhansali, Dinesh Kamath, V Shankar, Dhiraj Gambhire, Rajendrakumar H Jani, Shashank Joshi, Pankaj Patel
Dual PPARα/γ can improve both metabolic effects and minimized the side effects caused by either PPARα or PPARγ agonist. The PRESS V study was aimed to evaluate the safety, tolerability, and efficacy of saroglitazar 2 mg and 4 mg capsules (Lipaglyn™; Zydus Code: ZYH1) as compared to high dose pioglitazone in patients with diabetic dyslipidemia. In this 26-week double-blind, parallel arm, phase 3 study patients with hypertriglyceridemia with type 2 diabetes mellitus (BMI > 23 kg/m(2); hypertriglyceridemia: TG > 200 to 400 mg/dL; glycosylated hemoglobin [HbA1c] >7 to 9%) were enrolled from 14 sites in India...
January 2014: Journal of Diabetes Science and Technology
Rajendrakumar H Jani, Vikas Pai, Pramod Jha, Gunjan Jariwala, Satinath Mukhopadhyay, Anil Bhansali, Shashank Joshi
BACKGROUND: Dyslipidemia due to diabetes is characterized by hypertriglyceridemia and reduced levels of high-density lipoprotein cholesterol (HDL-C) and elevated or normal levels of low-density lipoprotein cholesterol (LDL-C) in type 2 diabetes mellitus (T2DM). The objectives of this Phase III study were to evaluate the safety, tolerability, and efficacy of saroglitazar (ZYH1) 2-mg and 4-mg tablets (Lipaglyn™; Zydus Cadila, Ahmedabad, India) compared with placebo in patients with diabetic dyslipidemia who are not controlled with atorvastatin 10 mg therapy...
February 2014: Diabetes Technology & Therapeutics
Rajendra H Jani, Kevinkumar Kansagra, Mukul R Jain, Harilal Patel
BACKGROUND AND OBJECTIVES: Dyslipidaemia is a major cardiovascular risk factor associated with type 2 diabetes mellitus. Saroglitazar (ZYH1) is a novel peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPARα and moderate PPARγ activity. It has been developed for the treatment of dyslipidaemia and has favourable effects on glycaemic parameters in type 2 diabetes mellitus. The objective of this phase 1 study was to evaluate the pharmacokinetics, safety and tolerability of saroglitazar in healthy human subjects...
November 2013: Clinical Drug Investigation
Ritesh Agrawal
The new chemical entity (NCE) has been knocked as novel antidiabetic agent, e.g. Saroglitazar. Saroglitazar is a drug for the treatment of Type II diabetes. Saroglitazar is marketed under the trade name Lipaglyn, developed by the Zydus Cadila. Lipaglyn is the first indigenously developed NCE by any Indian pharmaceutical company, ever. Lipaglyn has been approved for the treatment of Type II diabetes by the Drug Controller General of India in June 2013. Lipaglyn is indicated for the patients suffering from diabetes dyslipidemia...
February 2014: Current Drug Targets
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