saroglitazar and Diabetes-Mellitus--Type-2

Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD.. A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates.. Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids.. Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).

Topics: Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR-gamma Agonists; Triglycerides

Non-alcoholic fatty liver disease (NAFLD) affects one-third of the population worldwide, of which a substantial number of patients suffer from non-alcoholic steatohepatitis (NASH). NASH is a severe condition characterized by steatosis and concomitant liver inflammation and fibrosis, for which no drug is yet available. NAFLD is also generally conceived as the hepatic manifestation of the metabolic syndrome. Consequently, well-established drugs that are indicated for the treatment of type 2 diabetes and hyperlipidemia are thought to exert effects that alleviate the pathological features of NASH. One class of these drugs targets peroxisome proliferator-activated receptors (PPARs), which are nuclear receptors that play a regulatory role in lipid metabolism and inflammation. Therefore, PPARs are now also being investigated as potential anti-NASH druggable targets. In this paper, we review the mechanisms of action and physiological functions of PPARs and discuss the position of the different PPAR agonists in the therapeutic landscape of NASH. We particularly focus on the PPAR agonists currently under evaluation in clinical phase II and III trials. Preclinical strategies and how refinement and optimization may improve PPAR-targeted anti-NASH drug testing are also discussed. Finally, potential caveats related to PPAR agonism in anti-NASH therapy are stipulated.

Topics: Chalcones; Diabetes Mellitus, Type 2; Drug Development; Fatty Liver; Humans; Hypoglycemic Agents; Inflammation; Liver; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Phenylpropionates; Pioglitazone; Propionates; Pyrroles

Diabetes mellitus and concomitant dyslipidemia, being referred to as 'diabetic dyslipidemia', are the foremost detrimental factors documented to play a pivotal role in cardiovascular illness. Diabetic dyslipidemia is associated with insulin resistance, high plasma triglyceride levels, low HDL-cholesterol concentration and elevated small dense LDL-cholesterol particles. Maintaining an optimal glucose and lipid levels in patients afflicted with diabetic dyslipidemia could be a major task that might require a well-planned diet-management system and regular physical activity, or otherwise an intake of combined antidiabetic and antihyperlipidemic medications. Synchronized treatment which efficiently controls insulin resistance-associated diabetes mellitus and co-existing dyslipidemia could indeed be a fascinating therapeutic option in the management of diabetic dyslipidemia. Peroxisome proliferator-activated receptors α/γ (PPARα/γ) dual agonists are such kind of drugs which possess therapeutic potentials to treat diabetic dyslipidemia. Nevertheless, PPARα/γ dual agonists like muraglitazar, naveglitazar, tesaglitazar, ragaglitazar and aleglitazar have been reported to have undesirable adverse effects, and their developments have been halted at various stages. On the other hand, a recently introduced PPARα/γ dual agonist, saroglitazar is an emerging therapeutic agent of glitazar class approved in India for the management of diabetic dyslipidemia, and its treatment has been reported to be generally safe and well tolerated.. Some additional and new compounds, at initial and preclinical stages, have been recently reported to possess PPARα/γ dual agonistic potentials with considerable therapeutic efficacy and reduced adverse profile. This review sheds light on the current status of various PPARα/γ dual agonists for the management of diabetic dyslipidemia.

Topics: Diabetes Mellitus, Type 2; Disease Management; Dyslipidemias; Humans; Insulin Resistance; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles

Saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India.. In this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study.. In 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies.. Saroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Hypolipidemic Agents; India; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Signal Transduction; Time Factors; Treatment Outcome

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. Saroglitazar , a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters.. This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events.. Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.

Topics: Animals; Atherosclerosis; Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dyslipidemias; Glycated Hemoglobin; Humans; Lipids; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Risk Factors

Lowering postprandial lipemia may mitigate cardiovascular risk in patients with diabetic dyslipidemia. This study was aimed to investigate whether saroglitazar suppresses postprandial lipemia in patients with diabetes and dyslipidemia.. This was a 12-week, prospective, multicenter, randomized, double-blinded, placebo-controlled study of saroglitazar in patients with diabetes and dyslipidemia. Thirty patients were randomized (1:1) to receive saroglitazar 4 mg or placebo orally once daily with metformin for 12 weeks. The primary endpoint was change in plasma triglyceride (TG) area under the curve (AUC) on a standardized 8-h fat tolerance test.. Thirty participants were randomized for interventions and eventually data of 19 participants qualified for per protocol analyses. Mean (SD) age in saroglitazar was 53.1 (8.8) years and 54.9 (7.7) years in placebo group. After 12 weeks, saroglitazar significantly lowered postprandial TG-AUC by - 458.3 (144.0) (- 25.7%, 95% CI - 765.1 to - 151.4) versus an increase of + 10.9 (157.9) (+ 0.5%, 95% CI - 325.6 to 347.3) mg/dL h in placebo group (P < 0.05). Saroglitazar lowered postprandial TG incremental AUC versus placebo: - 329.4 (89.9) (- 59%) versus + 80.4 (99.4) (+ 10%) mg/dL h (P < 0.05). HbA1c (%) decreased by - 0.36 (0.42) in the saroglitazar group as compared to an increase of + 1.26 (0.46) (P < 0.05) with placebo.. The saroglitazar treatment significantly improved postprandial TGs in people with diabetic dyslipidemia.. Clinical Trial Registry of India; trial Registration No.: CTRI/2015/06/005845 and Date of registration: June 02, 2015.

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hyperlipidemias; Hypoglycemic Agents; India; Male; Metformin; Middle Aged; Phenylpropionates; Placebos; Postprandial Period; PPAR alpha; PPAR gamma; Pyrroles; Triglycerides

The potential for PPAR agonists to positively affect risk of cardiovascular disease in patients with type 2 diabetes (T2DM) is of persistent attention. The PRESS XII study primarily aimed to evaluate the efficacy and safety of saroglitazar (2 mg and 4 mg) as compared to pioglitazone 30 mg on glycemic control in patients with type 2 diabetes mellitus.. In this randomized double-blind study, patients with T2DM [glycosylated hemoglobin (HbA1c) ≥ 7.5%] were enrolled from 39 sites in India. Patients received once-daily doses of either saroglitazar or pioglitazone (1:1:1 allocation ratio) for a total of 24 weeks. Patients were continued in a double blind extension period for an additional 32 weeks. Efficacy evaluations of glycemic parameters [HbA1c (Primary endpoint at week 24), FPG and PPG] and other lipid parameters (TG, LDL-C, VLDL-C, HDL-C, TC, Non HDL-C, Apo A1 and Apo B) were conducted at week 12, 24 and 56 and compared to the baseline levels. The efficacy analyses were performed by using paired t-test and ANCOVA model.. A total of 1155 patients were enrolled in this study. The baseline characteristics were similar between the three treatment groups. The within group mean (± SD) change in HbA1c (%) from baseline of the saroglitazar (2 mg and 4 mg) and pioglitazone treatment groups at week 24 were: - 1.38 ± 1.99 for saroglitazar 2 mg; - 1.47 ± 1.92 for saroglitazar 4 mg and - 1.41 ± 1.86 for pioglitazone, respectively. Statistically significant reduction from baseline in HbA1c was observed in each treatment group at week 24 with p-value < 0.016. There was a significant reduction in TG, LDL-C, VLDL-C, TC and Non HDL-C with a significant increase in HDL-C from baseline levels (< 0.016). Most of the AE's were 'mild' to 'moderate' in severity and were resolved by the completion of the study.. Saroglitazar effectively improved glycemic control and lipid parameters over 56 weeks in patients of T2DM receiving background metformin therapy and has a promising potential to reduce the cardiovascular risk in T2DM patients. Trial registration CTRI/2015/09/006203, dated 22/09/2015.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Dyslipidemias; Glycated Hemoglobin; Humans; Hypoglycemic Agents; India; Lipids; Phenylpropionates; Pioglitazone; Prospective Studies; Pyrroles; Time Factors; Treatment Outcome

Saroglitazar is a dual PPAR-α/γ agonist approved for the treatment of diabetic dyslipidemia. In addition to reduction in atherogenic lipids, it may also contribute to improvement in insulin sensitivity through PPAR-α/γ agonism, which remains unexplored. We conducted a randomized, double-blind, placebo-controlled trial in treatment-naive T2DM individuals with serum triglyceride >150 mg/dL. Participants were randomized to receive either saroglitazar 4 mg or placebo (1:1) daily for 4 months (n = 30). Insulin sensitivity (SI

Topics: Adult; Diabetes Mellitus, Type 2; Double-Blind Method; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypertriglyceridemia; Insulin Resistance; Lipids; Male; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles

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.. This was a 16-week prospective, multicenter, randomized, double-blind, placebo controlled, three-arm Phase III study in subjects with hypertriglyceridemia (>200 and <500 mg/dL) with T2DM not controlled with atorvastatin 10 mg. The study consisted of a run-in period of 4 weeks of life-style modification followed by 12 weeks of treatment with saroglitazar (2-mg or 4-mg) or placebo tablets. The primary end point was the change in plasma triglyceride level compared with baseline and the placebo arm at the end of Week 12. The secondary exploratory end points were change in lipid profile and fasting plasma glucose at Week 12. In total, 302 subjects were randomized to receive one of the treatments, saroglitazar 2 mg (n=101) or saroglitazar 4 mg (n=99), or matching placebo (n=102). Patients who received study medication and had undergone at least one post baseline efficacy evaluation were included in the efficacy analysis.. At Week 12, saroglitazar 2-mg and 4-mg tablets significantly reduced mean plasma triglyceride levels by -45.5±3.03% and -46.7±3.02% (mean±SE), respectively, and the difference was significant (P<0.001) compared with placebo. Saroglitazar 2 mg demonstrated significant decrease in levels of non-HDL-C, very LDL-C, total cholesterol, and fasting plasma glucose. Additionally, saroglitazar 4 mg also significantly reduced LDL-C and apolipoprotein B levels. Saroglitazar was found to be safe and well tolerated by patients.. Saroglitazar appeared to be an effective and safe therapeutic option for improving hypertriglyceridemia in patients with T2DM.

Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Atorvastatin; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Fasting; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Male; Middle Aged; Patient Safety; Phenylpropionates; Prospective Studies; Pyrroles; Risk Reduction Behavior; Treatment Failure; Treatment Outcome; Triglycerides

To date, there is no satisfactory and effective therapy available to cure type 2 diabetes mellitus (T2DM). This present work is focused on plant extracts and the effect of saroglitazar and TET genes on oxidative stress and inflammation in vitro adipocytes. Aqueous extracts of

Topics: Adipocytes; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Down-Regulation; Gene Expression; Glucose; Hypoglycemic Agents; Inflammation; Lipoproteins, LDL; Momordica charantia; Phenylpropionates; Plant Extracts; Pyrroles; Tamarindus

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor-type transcription factors that consist of three subtypes (α, γ, and β/δ) with distinct functions and PPAR dual/pan agonists are expected to be the next generation of drugs for metabolic diseases. Saroglitazar is the first clinically approved PPARα/γ dual agonist for treatment of diabetic dyslipidemia and is currently in clinical trials to treat non-alcoholic fatty liver disease (NAFLD); however, the structural information of its interaction with PPARα/γ remains unknown. We recently revealed the high-resolution co-crystal structure of saroglitazar and the PPARα-ligand binding domain (LBD) through X-ray crystallography, and in this study, we report the structure of saroglitazar and the PPARγ-LBD. Saroglitazar was located at the center of "Y"-shaped PPARγ-ligand-binding pocket (LBP), just as it was in the respective region of PPARα-LBP. Its carboxylic acid was attached to four amino acids (Ser289/His323/His449/Thr473), which contributes to the stabilization of Activating Function-2 helix 12, and its phenylpyrrole moiety was rotated 121.8 degrees in PPARγ-LBD from that in PPARα-LBD to interact with Phe264. PPARδ-LBD has the consensus four amino acids (Thr253/His287/His413/Tyr437) towards the carboxylic acids of its ligands, but it seems to lack sufficient space to accept saroglitazar because of the steric hindrance between the Trp228 or Arg248 residue of PPARδ-LBD and its methylthiophenyl moiety. Accordingly, in a coactivator recruitment assay, saroglitazar activated PPARα-LBD and PPARγ-LBD but not PPARδ-LBD, whereas glycine substitution of either Trp228, Arg248, or both of PPARδ-LBD conferred saroglitazar concentration-dependent activation. Our findings may be valuable in the molecular design of PPARα/γ dual or PPARα/γ/δ pan agonists.

Topics: Binding Sites; Crystallography, X-Ray; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hypolipidemic Agents; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Protein Domains; Pyrroles; Recombinant Proteins

Saroglitazar, a dual peroxisome proliferator activated receptor α/γ agonist, approved for diabetic dyslipidemia (DD), is potential therapeutic option for non-alcoholic fatty liver disease (NAFLD). This prospective, observational, real-world study aimed to determine efficacy and safety of Saroglitazar in patients with NAFLD and DD. We included patients with DD and NAFLD who received Saroglitazar 4 mg once daily for 24 weeks. Blood investigations, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) (FibroScan) were compared at baseline and 24 weeks. Of 163 patients screened, 107 were included, and 101 completed 24 weeks treatment (mean age 50.4 ± 12.3 years, 78.5% males, mean body mass index 28.8 ± 4.2). After 24 weeks, alanine transaminase (ALT) reduced significantly from 94 (47-122) to 39 (31-49) (p < 0.0001) and aspartate aminotransferase (AST) (U/L) from 89 (43-114) to 37 (30-47) (p < 0.0001) and LSM (kPa) from 8.4 (7.1-9.3) to 7.5 (6.4-8.4) (p = 0.0261). CAP, glycated hemoglobin and lipid parameters also improved significantly. On linear regression, there was significant association between percent change in ALT and AST with TG reduction after treatment (p = 0.024 and 0.037 respectively).We conclude that Saroglitazar leads to significant improvement in transaminases, LSM, and CAP in NAFLD patients with DD.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Humans; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Prospective Studies; Pyrroles; Regression Analysis

The 76th American Diabetes Association (ADA) Scientific Sessions took place in New Orleans, Louisiana, USA. The meeting brought together scientists and professionals from a wide range of disciplines in the field of diabetes and provided a platform for networking, allowing experts and researchers to share ideas and learn about the significant advances in diabetes research, treatment and care. Over the course of the 5 days, participants received exclusive access to more than 2,500 original research presentations.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Phenylpropionates; Pyrroles

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. FFA-induced overexpression of TxNIP gene was mediated through the activation of its bona-fide trans activator, ChREBP. Further, Palmitate-induced impairment in AMPK-SIRT-1 pathway resulted in overexpression of ChREBP. While Fenofibrate, abrogated PA-induced TxNIP expression and ROS generation in skeletal muscle cells, Saroglitazar, a dual PPARα/γ-agonist, not only inhibited PA-induced TXNIP expression but also led to greater improvement in glucose uptake. Taken together, TxNIP appears to be an important factor in FFA-induced ROS generation and IR in skeletal muscle cells, which can be modulated for the management of this complex disorder.

Topics: AMP-Activated Protein Kinases; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biological Transport, Active; Carrier Proteins; Cell Line; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Fenofibrate; Glucose; Glucose Transporter Type 4; Insulin Resistance; Mice; Muscle Fibers, Skeletal; Nuclear Proteins; Palmitic Acid; Phenylpropionates; Pyrroles; Reactive Oxygen Species; Sirtuin 1; Thioredoxins; Transcription Factors

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. After a mean follow-up period of 14 weeks in 34 patients, treatment with Saroglitazar, in a dose of 4 mg daily, resulted in significant improvement in both glycaemic and lipid parameters. There were significant mean reductions of fasting plasma glucose (36.71 mg/dl; p = 0.0007), post-prandial plasma glucose (66.29 mg/dl; p = 0.0005), glycosylated haemoglobin (1.13%; p < 0.0001), total cholesterol (48.16 mg/dl; p < 0.0001), low- density lipoprotein cholesterol (24.04 mg/dl; p = 0.0048), triglyceride (192.78 mg/dl; p = 0.0001), non-high density lipoprotein cholesterol (48.72 mg/dl; p < 0.0001) and the ratio of triglyceride and high density lipoprotein cholesterol (5.30; p = 0.0006). There was no significant change in body weight, blood pressure, high-density lipoprotein cholesterol and serum creatinine.

Topics: Adult; Aged; Blood Glucose; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; India; Male; Middle Aged; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Treatment Outcome; Triglycerides

Topics: Berberine; Diabetes Mellitus, Type 2; Drug Approval; Drug Industry; Dyslipidemias; Humans; Hydroxychloroquine; Hypoglycemic Agents; India; Marketing; Phenylpropionates; Pyrroles

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. It also provides the option of a once-daily oral therapy. Saroglitazar regulates the lipid parameters as well as glycemic control. The present article describes Saroglitazar with its chemical synthesis and patent status with its summary of clinical studies.

Topics: Administration, Oral; Adult; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hypoglycemic Agents; India; Lipid Metabolism; Middle Aged; Phenylpropionates; Pyrroles; Young Adult