LIPAGLYN - The novel drug for treating Diabetic Dyslipidemia
combines lipid and glucose lowering effects in one single molecule.News Room
American Diabetic Association Annual Conference, New Orleans, LA, June 10-14, 2016
ADA 2016 – We had presented 1 Oral, 4 poster presentation including 2 Late Breaking and 2 abstract publication at 2016 American Diabetic Association Annual Conference, New Orleans, USA
# 73 ORAL - Efficacy of Dapagliflozin-Saroglitazar combination for treatment of NAFLD in young diabetics
Author
Prevalence of NAFLD and NASH are increasing worldwide and these are commonly associated with T2DM. Pharmacological treatment of NAFLD is still evolving. We recently showed Exenatide and Saroglitazar (a novel PPAR alpha/gamma agonist with anti-hyperlipidemic and insulin sensitizing property) combination as an effective regime for NAFLD in diabetic. With the aim to target pathophysiology of both hyperglycemia and hyperlipidemia for liver fat accumulation, we studied the effects of dapagliflozin in combination with Saroglitazar on hepatic fat content and other biochemical parameters with NAFLD.
56 patients (age 20-35 yrs) on dietary and metformin therapy received treatment with dapagliflozin (10 mg) and Saroglitazar (4mg) PO (n-28) [GROUP 1] or dapagliflozin alone 10mg (n-28) [Group 2] for 24 weeks. Age, BMI, diabetes duration and abnormal transaminases levels were comparable between the two groups. Hepatic Steatosis was measured by Transient Elastography (Fibroscan). Other parameters including weight, FPG, PPG, HbA1c, lipid profile, RFT, LFT were measured.
| Parameters | Group 1 (Dapagliflozin + Saroglitazar) | Group 2 (Dapagliflozin Only) | P Value (Changes between groups) | ||||
| Group 1 | Group 2 | ||||||
| Baseline | Week 24 | Change in Group 1 | Baseline | Week 24 | Change in Group 2 | ||
| HbA1c (%) | 8.2+-1.0 | 7.1+-0.4 | 1.2 | 7.9+-0.6 | 7.1+-0.4 | 0.87 | 0.8 (NS) |
| Triglyceride (mg/dl) | 399.2+-83 | 183.3+-47.4 | 215.9 | 373.9+-164.8 | 230.7+- 62.8 | 143.2 | 0.002 |
| Liver fat content (db/m) | 335.6+-36.6 | 204.8+-2w 6.1 | 130.7 | 324+-29 | 250.2+-30 | 38.3 | 0.001 |
| Reversibility of transaminitis (subgroup n/%) | n-18/64.2% | n-5/17.9% | 32.7 | n-17/60.7% | n-11/39.3% | 14.03 | 0.09 |
# 37 LB - One Year Post Marketing Surveillance Study of Saroglitazar in Patients with Diabetic Dyslipidemia
Author
Saroglitazar is the world’s first approved dual PPAR a/y agonist. It is currently approved in India for the treatment of hypertriglyceridemia in type 2 diabetes not controlled with statin. This was a post-marketing surveillance study conducted with the objective to evaluate the safety and efficacy of Saroglitazar 4mg once daily. Total 106 patients with diabetic dyslipidemia were included in this study.
The mean age of study population was 54.82 years and 66% participants were male. At baseline, all patients were on stable doses of metformin and 99% patients were on statin therapy. The mean baseline triglycerides (TG) and Non-HDL cholesterol were 252.69 mg/dl and 164.35 mg/dl respectively. All patients were prescribed Saroglitazar 4mg once daily without changing the doses of on-going statin therapy. At 12 months follow-up, the TG was reduced from 252.69 mg/dl to 161.55 mg/dl (p<0.0001) and non HDL-C level was reduced from 164.35 mg/dl to 107.02 mg/dl (p<0.0001). Mean HbA1c was also significantly reduced from 8.17% at baseline to 6.77% after 1 year Saroglitazar therapy in combination with other anti-diabetic medications (p<0.0001).
No major adverse event reported during 12 month follow-up. Saroglitazar treatment was found to be weight neutral. Saroglitazar is a potential add on therapeutic option for the treatment of hypertriglyceridemia in type 2 diabetes not controlled with statin alone.
| Follow-up* parameters | Baseline | 6-month follow- up* | 12-month follow- up* | P value |
| TG (mg/dL) | 252.69±58.32 | 192.54±35.84 | 161.55±34.27 | <0.0001 |
| LDL-C (mg/dL) | 165.737±49.69 | 135.20±37.81 | 110.45±29.62 | <0.0001 |
| VLDL-C (mg/dL) | 57.71±11.87 | 50.12±9.07 | 45.07±7.99 | <0.0001 |
| TC (mg/dL) | 223.82±33.93 | 181.45±27.01 | 152.39±24.11 | <0.0001 |
| non HDL-C (mg/dL) | 164.35±33.98 | 129.07±27.36 | 107.02±24.37 | <0.0001 |
# 40 LB - Efficacy and Safety of Saroglitazar in Indian Diabetics — Two Year Data
Author
Saroglitazar is a dual PPAR alpha / gamma agonist available in India for more than 2 years. Patients were evaluated for efficacy and safety of Saroglitazar (4 mg). A total of 108 patients were followed over 24 months with a mean duration of diabetes of 9.3 years. The demographic profile was mean age of 61 years, mean BMI 28 kg/m2 . 64.8 %patients were male and 45.36% were on Statin therapy and all patients were on metformin therapy. 71.28% patients also had a second agent for diabetes treatment at baseline.
The baseline Hb1c levels were 8.8 % and Triglycerides were 351 mg/dl. Two years of Saroglitazar lead to a significant absolute reduction of 0.7 % in glycosylated Hb in patients. There was a significant improvement in Fasting and Post-prandial plasma glucose. Addition of 4 mg Saroglitazar led to 41% reduction (P < 0.001) in Triglycerides, LDL-C (12%), Total cholesterol (16.3%) and non HDL-C (28%). Renal, hepatic, cardiac functions which were monitored every 3 months and no serious adverse events were seen. No edema or weight gain was also reported.
Saroglitazar is a novel treatment agent in Type2 DM with dyslipidemia . And has long term glycemic and lipid control with a two years safety profile.
# 1111 P - Anti-diabetic Efficacy of Saroglitazar and its Combinations with other Drugs in db/db Mice
Author
Saroglitazar is a novel dual PPARα/γ agonist that showed significant triglyceride-lowering and insulin-sensitizing effects in various preclinical models. In present study, we have compared the anti-diabetic activity of saroglitazar with other anti-diabetic drugs in db/db mice, a genetic model of T2DM. Saroglitazar, canagliflozin and sitagliptin were administered to 11-12 week old db/db mice at the dose of 1 mg/kg/day for 8 weeks. Saroglitazar and canagliflozin showed significant 44 and 24 % reduction in HbA1c and 63% and 36% reduction in glucose levels, respectively whereas sitagliptin did not showed any significant effect on blood glucose and HbA1c levels.
Saroglitazar also showed the significant reduction in serum triglycerides (53%) and nonesterified fatty acids (43%), which was not shown by canagliflozin as well as sitagliptin. The glucose AUC in OGTT study showed that saroglitazar and canagliflozin showed significant 66 and 39 % improvements in glucose tolerance whereas sitagliptin showed 27 % improvement.
In most T2DM patients, effective management of blood glucose requires combination therapy, hence saroglitazar was evaluated in combination with various anti-diabetic drugs like metformin, dipeptidyl peptidase IV inhibitors (sitagliptin or saxagliptin or vildagliptin), GLP-1 receptor agonist (exenatide or liraglutide) or insulin in db/db mice. Once-daily oral treatment of db/db mice with saroglitazar (0.1 mg/kg) along with other ant diabetic drugs for 14 days resulted in additive or synergistic anti-diabetic activity in terms of glucose lowering and improvement in glucose tolerance.
Overall, the results suggest that saroglitazar; an agent approved & available in India for treatment of diabetic dyslipidemia since 2013, showed better anti-diabetic activity than canagliflozin and sitagliptin in db/db mice model and also showed additive or synergistic antidiabetic activity with currently available anti-diabetic drug having diverse mechanism of action.
# 1133 P - Study of Saroglitazar in Treatment of Pre-diabetes with Dyslipidemia
Author
Saroglitazar, a dual PPAR α/γ agonist, is approved in India for the treatment of diabetic dyslipidemia and type 2 diabetes with hypertriglyceridemia not controlled with statin. This is an observational, single center study, conducted in patients with pre-diabetes and dyslipidemia to evaluate the safety and efficacy of Saroglitazar. Subjects with baseline HbA1c 5.7-6.4% and dyslipidemia as per NCEP criteria were enrolled in this study. Subjects with on-going medications affecting blood glucose or lipids were excluded from the study.
Total 40 patients (28 male participants) with mean age of 48.15 years were enrolled in the study. The mean baseline HbA1c and triglycerides were 6.3% and 348 mg/dL respectively. All subjects were given Saroglitazar 4mg once daily for 24 weeks. The change in lipid parameters, HbA1c, liver enzymes, and kidney functions were evaluated at 24 weeks by using paired t-test. At 24 weeks, there were significant improvements in HbA1c level and lipid parameters (table).
There was no adverse effect of Saroglitazar on liver enzymes or kidney function at week 24. One patient reported with an episode of diarrhea which was resolved with antimicrobials without interrupting study medication. This is the first data of Saroglitazar in patients with pre-diabetes and dyslipidemia.
| Laboratory parameters | Baseline (n=40) | 24 weeks follow-up n=40) | Absolute change from baseline | % change from baseline | P Value |
| Triglycerides (mg/dL) | 348.0± 86.98 | 216.4± 72.34 | -131.5± 48.64 | -38.7± 10.72 | <0.0001 |
| LDL-C (mg/dL) | 209.8 ± 47.67 | 177.9 ± 47.56 | -31.9 ± 14.225 | -15.7 ± 8.47 | <0.0001 |
| HDL-C (mg/dL) | 44.8 ± 5.71 | 49.0 ± 6.13 | 4.2 ± 2.39 | 9.6 ± 5.54 | <0.0001 |
| Non HDL-C (mg/dL) | 278.6 ± 42.38 | 224.1 ± 47.15 | -54.5 ± 25.11 | -19.9 ± 10.35 | <0.0001 |
| HbA1c (%) | 6.3 ± 0.16 | 5.5 ± 0.30 | -0.7 ± 0.25 | - | <0.0001 |
| Alanine aminotransferase (U/L) | 26.9 ± 6.16 | 24.6 ± 6.61 | -2.3 ± 6.12 | -6.7 ± 23.14 | 0.024 |
| Serum Creatinine (mg/dL) | 1.0 ± 0.17 | 1.0 ± 0.14 | 0.0 ± 0.18 | 6.1 ± 19.46 | 0.21 |
# 2182 PUB - Effect of Saroglitazar on Metabolic Parameters in Indian Patients with Diabetic Dyslipidemia - A 40 week, Retrospective Analysis
Author
Saroglitazar, a novel dual peroxisome proliferator-activated receptor (α/γ) agonist, is available in India for the treatment of diabetic dyslipidemia (DD) since July 2013. This study was a multicenter, retrospective analysis of patients with type 2 diabetes mellitus and dyslipidemia. All patients were prescribed Saroglitazar 4 mg once daily.
Objective of this study was to evaluate the efficacy and safety of Saroglitazar in Indian DD patients. Baseline patient (n=74) demographics were: age 52.36 ± 9.61 yr (mean ± SD), body weight 68 ± 10.46 kg (mean ± SD); male 46, female 28. At baseline, all patients were on anti-hyperglycemic medication and 65% patients were on statin therapy. Mean duration of follow-up was 40 weeks.
After 40 weeks of follow up, there were statistically significant changes in lipid and glycemic parameters (table). Liver enzyme, alanine aminotransferase (ALT) was significantly reduced from 43.19±24.24 U/L to 30.23±17.71 U/L (mean ± SD; p<0.0001). No serious adverse events were reported during entire study follow-up. Adverse effects reported were mild and transient. No significant change was observed in body weight and serum Creatinine level. These results are consistent with previous report with smaller number of patient and smaller duration of study.
| Parameters | Baseline | Follow-up | Mean change (40 weeks) | P-value |
| FPG (mg/dL) | 151.9 ± 57.58 | 120.51 ± 33.44 | -31.39 | 0.0001 |
| Triglycerides (mg/dL) | 343.27 ± 211.65 | 168.88 ± 152.45 | -193.58 | <0.0001 |
| HDLc (mg/dL) | 38.3 ± 10.59 | 38.21 ± 10.07 | -0.086 | 0.94 |
| LDLc (mg/dL) | 105.22 ± 41.98 | 90.74 ± 31.28 | -14.48 | 0.0039 |
| Non HDLc (mg/dL) | 150.18 ± | 50.37 111.69 ± 48.86 | -38.48 | <0.0001 |
# 2269 PUB - Effect of Saroglitazar on non HDL-C in Diabetic Dyslipidemia
Author
Non HDL-C is a useful predictor of adverse cardiovascular outcome in patients treated with statin and is a recommended lipid target especially when triglycerides are greater than 200 mg/dL.
Saroglitazar is a novel dual PPARα/γ agonist approved in India for the treatment of hypertriglyceridemia in type 2 diabetes not controlled by statins. This is a single centre, observational study conducted to evaluate the effect of Saroglitazar on non HDL-C at 1 year follow-up in patients with diabetic dyslipidemia.
Total 81 patients with type 2 diabetes and dyslipidemia were prescribed Saroglitazar 4mg once daily for 1 year to evaluate effect on non HDL-C. The mean age of these patients was 55.43 years with 71.6% male participants. At baseline, all were on one or more anti-diabetic medication and 81.48% were on statins (atorvastatin 5-10 mg/d or Rosuvastatin 5-10 mg/d). At 1 year follow-up, Saroglitazar treatment showed significant reduction in non HDL-C from 183.10±33.81 mg/dL at baseline to 129.09±20.70 mg/dL (p =0.0001). Other lipid parameters like triglycerides and HDL-C also improved significantly from 294.14±83.90 mg/dL and 41.35±4.63 mg/dL at baseline to 130.67±32.7 mg/dL and 45.04±5.43 mg/dL respectively at 1 year follow-up.
There were no reports on weight gain or any other adverse events. Saroglitazar in diabetic dyslipidemia has been found effective in reducing not only non HDL-C but also other lipid abnormalities.
Press Release: Zydus receives approval from USFDA to initiate Phase 2 clinical trials of Saroglitazar (LipaglynTM)in patients with Non-Alcoholic Steatohepatitis (NASH) of the liver in USA Zydus Group, a research-driven, global healthcare provider, today announced that USFDA has approved the company’s plan to initiate a Phase 2 clinical trial of Saroglitazar in patients with Non-Alcoholic Steatohepatitis (NASH) of the liver. This randomized, double-blind Phase 2 trial will evaluate Saroglitazar 1 mg, 2mg and 4 mg Vs. Placebo.
Press Release: Zydus gets USFDA nod for clinical trials of Saroglitazar Ahmedabad: Zydus Group has received an approval from US Food and Drug Administration (USFDA) for initiating a phase-2 clinical trial of Saroglitazar. its new drug for treating high fat levels in body due to diabetes, obesity, and sedentary habits in patients suffering from severe hypertriglyceridemia. The trial will be conducted across several medical sites in the US.
American Diabetic Association Annual Conference, Boston, MA, June 6 -9, 2015
ADA 2015 – We had presented 8 poster presentation including 1 Late Breaking trial at American Diabetic Association Annual Conference, Boston 126-LB. Saroglitazar in Diabetic Dyslipidemia: 1-Year Data S.R. Joshi: Consultant; Author; Zydus Group, Bayer Zydus Pharma,. Speaker's Bureau; Author; Sanofi, Abbott, USV, Franco Indian, Ranbaxy, PHFI, MSD, Novartis, J & J, Roche, Novo Nordisk, Marico, Emcure. S. Ghosh: Advisory Panel; Author; Zydus Group. P. Shah: None. A.D. Jaiswal: Employee; Author; Zydus Lifesciences Ltd. P. Patel: Employee; Author; Zydus Lifesciences Ltd. 712-P. To Assess the Effect of 4mg Saroglitazar on Patients of Diabetes Dyslipidemia with Nonalcoholic Fatty Liver Disease for 24 Weeks at Diabetes Care Centre, June 6, 2015 B.D. Saboo: None. A. Prajapati: None. S. Joshi: None. S. Bhandari: None. A.N. Shah: None. A. Jaiswal: None. D. Hasnani: None. 1957-P - Saroglitazar Shows Therapeutic Benefits in Mouse Model of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH), June 8, 2015
M.R. Jain: Employee; Author; Cadila Healthecare Limited. S.R. Giri: Employee; Author; Cadila Healthecare Limited. B. Bhoi: Employee; Author; Cadila Healthecare Limited. C. Trivedi: Employee; Author; Cadila Healthecare Limited. R. Ranvir: Employee; Author; Cadila Healthecare Limited. S. Kadam: Employee; Author; Cadila Healthecare Limited. P. Swain: Employee; Author; Cadila Healthecare Limited. P.R. Patel: Employee; Author; Cadila Healthecare Limited. NAFLD and NASH are common clinico-pathological conditions affecting millions of patients worldwide. Although numbers of therapeutic options have been explored for management of NAFLD/NASH, no pharmacological treatment is yet approved. Saroglitazar is a novel PPAR α/γ agonist that shows anti-hyperlipidemic, anti-hyperglycemic and insulin sensitizing effects. C57BL/6 mice fed with choline-deficient amino acid-defined, high-fat diet (CDAHFD) containing 60 kcal% fat,is known to develop a condition similar to human NASH. Following eight-weeks of CDAHFD feeding, animals were treated with saroglitazar (1 and 3 mg/kg/day) or fenofibrate (300 mg/kg/day) for 8 weeks and maintained on CDAHFD. Saroglitazar (1 and 3 mg/kg) showed dose-dependent and significant (p < 0.001) reduction in serum ALT (38 and 57 %), AST (33 and 56%) and MCP-1 (41 and 42%) levels when compared with untreated (CDAHFD-fed) disease control animals. Liver lipid accumulation was also significantly attenuated (60-70%, P < 0.001) by saroglitazar treatment.Fenofibrate (300 mg/kg) also showed reduction in serum ALT (44%), AST (51%)and MCP-1 (37%), however, the elevated liver lipids were not affected by fenofibrate treatment. The expression of pro-inflammatory genes such as MMP-9, TNF-α and pro-fibrotic marker genes such as α-SMA were also suppressed in saroglitazar-treated animals. Histological investigation of liver revealed reduction of steatosis, ballooning, inflammation and fibrosis in animals treated with saroglitazar. The NASH Score of saroglitazar (3mg/kg) group was 4.7 vs 17.8 for untreated control animals and 16.4 for fenofibrate-treated animals. The results indicate that saroglitazar appears to be a promising drug for the management of NAFLD/NASH. 704-P - Effect of Saroglitazar, a Dual PPAR-α/γ agonist, on Lipid and Glycemic Parameters in Indian Patients with Diabetic Dyslipidemia_A 27-Week, Retrospective Analysis, June 6, 2015 S. Chatterjee: None. A. Majumder: None. A.D. Jaiswal: Employee; Author; Zydus Lifesciences Ltd. Saroglitazar, a novel dual peroxisome proliferator-activated receptor (α/γ) agonist, is available in India for the treatment of diabetic dyslipidemia (DD) since Sept 2013. This is a multicenter, retrospective analysis of patients, having type 2 diabetes and dyslipidemia, who were prescribed saroglitazar 4 mg once daily. Objective of this study was to evaluate the safety and efficacy of saroglitazar in Indian patients with DD. Baseline patient (N=31) demographics were: age 54 ± 9.98 yr (mean ± SD), body weight 69.4±9.88 kg (mean ± SD). 58% patients were male. At baseline, all patients were on antidiabetic medication and 68% patients were on statin therapy. Mean duration of follow up was 27 weeks. After 27 weeks’ follow up, there were statistically significant improvements in lipid and glycemic parameters (Table). Liver enzyme, alanine aminotransferase (ALT) was significantly reduced from 52.08±26.74 U/L to 34.92±26.4 U/L (mean ± SD) after 27 weeks’ follow up (n=13). There was no significant change observed in serum creatinine value at follow up. No serious adverse events were reported during entire period of study follow up. Saroglitazar was not associated with edema or weight gain. In conclusion, saroglitazar is safe and effective for the treatment of type 2 diabetes with dyslipidemia.
India, June 4, 2016
NASH is the area of significant unmet medical need in the USA with an estimated 6.5 million adults in the United States and five major European countries having advanced NASH. NASH is a liver disease in which fat accumulates in the liver. Obesity, insulin resistance, diabetes and lipid disorders lead to NAFLD which progresses to a lethal NASH situation. The diagnosis of NASH is most commonly carried out using liver biopsy and this condition can progress to cirrhosis and liver failure. Liver transplantation is the only treatment for advanced cirrhosis with liver failure. NASH ranks as one of the major causes of cirrhosis in America, behind hepatitis C and alcoholic liver disease. Biotech Analysts estimate the worldwide market for NASH medicines to reach USD 35-40 billion by 2025.
Speaking on the development, Mr. Pankaj Patel, Chairman and Managing Director of Zydus Group said, “NASH is an area of unmet healthcare need as there are currently no drugs approved for the treatment of NASH. Saroglitazar has significant and differentiated effect on hepatic steatosis, while it shows all other beneficial effects on reducing inflammation and fibrosis in the liver in NASH models. With a Phase III trial in biopsy proven NASH patients on-going in India and a Phase II trial in NASH patients planned in USA, we are committed towards developing this drug for millions of patients suffering from NASH”.
Dr. Naga Chalasani, MD, FACG, David W. Crabb Professor & Director, Division of Gastroenterology and Hepatology, Indiana University School of Medicine will be the Principal investigator on this planned trial. This trial will be conducted across several medical sites in the USA., which will measure several parameters including the reduction in liver enzymes (serum ALT levels), liver stiffness (FibroScan®), liver fat content via MRI-PDFF, cytokeratin-18 (CK-18), enhanced liver fibrosis (ELF), aspartate aminotransferase-to-platelet ratio index (APRI), lipids, insulin resistance as well as glycemic control.
Zydus had earlier initiated a 52 week Phase III clinical trial of Lipaglyn™ in India to treat patients with biopsy proven NASH. Saroglitazar has demonstrated good efficacy in animal models of NASH, along with associated biomarkers. It has reduced hepatic steatosis, ballooning, inflammation and fibrosis in liver. The recently concluded phase 2 studies of Saroglitazar in patients with biopsy proven NASH has shown improvement in liver enzymes along with favourable effects on lipid and Glycemic indices.
For more details visit http://timesofindia.indiatimes.com/city/delhi/Zydus-gets-FDA-nod-for-phase-II-clinical-trial-of-Saroglitazar/articleshow/52587492.cms
For more details visit http://www.thehindubusinessline.com/companies/announcements/others/zydus-receives-approval-from-usfda-to-initiate-phase-2-clinical-trials-of-saroglitazar-in-patients-with-nonalcoholic-steatohepatitis-nash-of-the-liver-in-usa/article8690559.ece
For more details visit http://www.financialexpress.com/article/industry/companies/zydus-gets-fda-nod-for-phase-ii-clinical-trial-of-saroglitazar/273863/
Times News Network
Saroglitazar or Lipaglyn is the first indigenously developed molecule and is currently app-roved in India as a prescription medicine for the treatment of hypertriglyceridemia and diabetic dyslipidemia in patients with Type-2 diabetes not controlled by statins.
“Zydus is committed to develop Lipaglyn (Saroglitazar) for millions of patients living with severe hypertriglyceridemia and fatty liver diseases,” said Pankaj Patel, chairman and managing director of Zydus Group.
According to Zydus, more than four million American adults are living with severe hypertriglyceridemia. High triglyceride levels can lead to increased triglyceride accumulation in the pancreas which puts patients at very high risk of pancreatitis, a serious and potentially life-threatening ill-ness. In addition, excessive accumulation of triglycerides in the liver can cause serious conditions like Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH).
NASH is currently the third most common reason for liver transplants in the US. It is estimated that about 6.5 million adults in the US and the five major European countries have advanced NASH. Currently no drugs are approved by the USFDA for treating NASH. The peak market for medicines is estimated at $35 billion to $40 billion by 2025.
For more details visit http://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/zydus-gets-usfda-nod-for-clinical-trials-of-sarolitazar/articleshow/49829067.cms
June 7, 2015
Authors
Disclosures
Saroglitazar is the world's first commercially available Dual PPAR α and γ agonist which was launched in September 2013 in India. The objective of this post-marketing surveillance study was to evaluate the safety and efficacy of saroglitazar for 1 year follow up in clinical practice. It was a multicenter, phase 4 study conducted all over India. Total 236 patients with diabetic dyslipidemia who were prescribed saroglitazar 4mg daily were evaluated for lipid and glycemic parameters at baseline, 3 month, 6 month, 9 month and 12 month follow up. Baseline patient demographics were: age 52 ± 10 year (mean ± SD), average duration of diabetes 5.91 year, and BMI 28.8 ± 3.99 kg/m2 (mean ± SD). At baseline, 89% and 38.6% patients were reported to be on antidiabetic and statin therapy respectively. Metformin was the most commonly reported in 72% patients followed by sulfonylureas (66.9%), gliptins (16.1%), insulin (20.8%) and pioglitazone (4.7%). One year treatment with saroglitazar resulted into significant improvement in glycemic and lipid parameters (results are shown in Table). There were no serious adverse events reported. Saroglitazar was found to be safe, well tolerated and was not associated with edema or weight gain. This is the first data of one year safety and efficacy of saroglitazar in a real world setting which clearly demonstrated the dual action of glucose and lipid lowering.
Laboratory parameter Baseline 3 month follow
up6 month follow
up1 year follow
upAbsolute change at
1 yearP value% % change at 1 year HbA1C (%) 8.5±1.06
7.9±0.87
7.5±0.78
6.9±0.76
-1.6±1.12
<0.0001 -- Fasting Plasma Glucose (mg/dL) 179.4±54.67
144.1±40.29
132.6±37.81
115.5±28.90
-63.9±44.20
<0.0001
-32.7±15.20 Post-prandial Plasma Glucose (mg/dL) 252.6±64.17
192.0±38.81
168.8±31.34
146.5±22.11
-106.1±63.56
<0.0001
-38.7±16.24 Triglycerides (mg/dL) 316.0±139.02
222.1±70.63
194.9±66.36
153.9±50.06
-162.1±136.73
<0.0001
-47.3±16.91 LDL-C (mg/dL) 131.8±43.78
114.8±35.55
108.1±31.9
96.7±30.13
-35.1±34.2
<0.0001
-24.1±21.72 HDL-C (mg/dL) 42.5±8.74
43.6±7.18
45.0±8.20
44.8±9.11
2.3±12.09
0.0044
9.2±29.59 Non HDL-C (mg/dL) 194.0±48.48
160.6±37.75
147.3±35.92
127.0±35.04
-67.1±45.54
<0.0001
-33.4±16.49
BANSHI D. SABOO, AAROHI PRAJAPATI, SHASHANK JOSHI, SUDHIR BHANDARI, ASHA N. SHAH, ASHOK JAISWAL, DHRUVI HASNANI, Ahmedabad, India, Mumbai, India, Jaipur, India
Disclosures
Non Alcoholic Fatty Liver Disease (NAFLD), a component of metabolic syndrome, is increasing rapidly in India along with increasing prevalence of insulin resistance, type 2 diabetes mellitus (T2DM) and obesity. Insulin resistance is the key underlying pathological mechanism in the genesis of NAFLD. NAFLD accounts for significant morbidity and mortality and the therapeutic options are limited. Saroglitazar is approved in India for the treatment of diabetic dyslipidemia (DD) and hypertriglyceridemia with T2DM not controlled by statin therapy. Saroglitazar has demonstrated significant reduction in triglycerides (TG) along with favorable effect on glycemic indices in diabetic patients. A clinical review was conducted to assess the effect of saroglitazar 4 mg on NAFLD in DD patients for 24 weeks at Diabetes Care Centre. Abdominal ultrasound, which is used for screening of NAFLD in asymptomatic patients with an incidental elevation of liver enzymes, was used to evaluate the effect of saroglitazar on hepatomegaly. Total 31 patients of either gender having T2DM with BMI of 28.2 ± 1.13 kg/m2 (mean ± SD) were included. The main outcome measures at 24 week follow up were body weight, assessment of hepatomegaly through transabdominal USG, BMI, liver enzymes (ALT, AST), glycemic parameters, lipid parameters (TG) and adverse effects if observed. Of the total 31 patients, 30 had hepatomegaly at entry and decrease in hepatomegaly was seen in 22 patients at 24 week follow up. Significant reductions were also seen in ALT (from 64.06 ± 6.19 U/L to 28.68 ± 3.15 U/L [mean ± SD]; p < 0.01), AST (from 61.64 ± 3.54 U/L to 28.68 ± 5.68 U/L [mean ± SD]; p < 0.01), TG (from 259.25 ± 37.87 mg/dL to 151.48 ± 53.56 mg/dL [mean ± SD]; p < 0.01), and HBA1c (from 9.04 ± 1.26% to 8.2 ± 1.24% [mean ± SD]; p < 0.01) at 24 week follow up. Effect of saroglitazar 4mg on NAFLD was favorable with improvement in grade of NAFLD, liver enzymes, lipid and glycemic parameters in DD patients.
MUKUL R. JAIN, SURESH R. GIRI, BIBHUTI BHOI, CHITRANG TRIVEDI, RAMCHANDRA RANVIR, SHEKHAR KADAM, PRABODHA SWAIN, PANKAJ R. PATEL, Ahmedabad, India
Disclosures
SANJAY CHATTERJEE, ANIRBAN MAJUMDER, ASHOK D. JAISWAL, Kolkata, India, Ahmedabad, India
Disclosures
| Baseline values (mean ± SD) | Follow up after 27 weeks(mean ± SD) | Mean change after 27 weeks follow up | P value | |
| Total cholesterol (mg/dL) | 197.54 ± 52.6 | 152.66 ± 43.06 | -44.88 | <0.0001 |
| LDL-C (mg/dL) | 111.43 ± 46.9 | 87.64 ± 32.6 | -23.78 | 0.0087 |
| HDL-C (mg/dL) | 39.2 ± 10.7 | 41.76 ± 14.21 | +2.56 | NS |
| Triglycerides (mg/dL) | 335.54 ± 161.23 | 148.19 ± 70.44 | -187.35 | <0.0001 |
| Non HDL-C (mg/dL) | 161.36 ± 52.8 | 104.07 ± 34.04 | -57.29 | <0.0001 |
| HbA1C (%) | 8.07 ± 1.75 | 6.84 ± 1.12 | -1.23 | <0.0006 |
| FPG (mg/dL) | 157 ± 54.16 | 118.09 ± 42.73 | -38.94 | 0.0019 |
703-P - Saroglitazar Shows Beneficial Effects on Insulin Sensitivity, Dyslipidemia, and Blood Pressure in Zucker Fatty Rats, June 6, 2015
MUKUL R. JAIN, SURESH R. GIRI, BIBHUTI BHOI, CHITRANG TRIVEDI, AKSHYAYA RATH, PRABODHA SWAIN, PANKAJ PATEL, Ahmedabad, India
Disclosures
M.R. Jain: Employee; Author; Cadila Healthcare Limited. S.R. Giri: Employee; Author; Cadila Healthcare Limited. B. Bhoi: Employee; Author; Cadila Healthcare Limited. C. Trivedi: Employee; Author; Cadila Healthcare Limited. A. Rath: Employee; Author; Cadila Healthcare Limited. P. Swain: Employee; Author; Cadila Healthcare Limited. P. Patel: Employee; Author; Cadila Healthcare Limited.
Saroglitazar is a novel Dual PPARα/γ agonist that has shown significant lipid-lowering and insulin-sensitizing effects with good safety profile in various preclinical models. In present study, we have evaluated insulin sensitizing, lipid lowering and antihypertensive potential of saroglitazar in insulin resistant Zucker fatty rats. Zucker fa/fa showed significantly higher (P < 0.001) blood pressure, serum TG and insulin levels than the lean control rats. Oral once-daily treatment of Zucker fa/fa rat with Saroglitazar for 15 days caused a dose-dependent increase in Glucose Infusion Rate (54 % and 127 % increase at 1 and 10 mg/kg respectively) during hyperinsulinemic-euglycemic clamp condition, indicating significant improvement in insulin sensitivity. In a separate experiment, once daily treatment of Zucker fa/fa with Saroglitazar at 4 mg/kg dose for 14 days, showed a significant decrease (P < 0.001) in SBP (22mmHg), serum TG (81%), serum insulin (76%) and HOMA-IR (79%). These changes were accompanied by up-regulation of serum adiponectin levels & expression of PPAR-related target genes in adipocytes and liver. Pioglitazone (10 mg/kg), showed similar decrease in SBP (21 mmHg), serum insulin (72%) and HOMA-IR (80%), however, the TG-lowering effect of pioglitazone was less pronounced (48% reduction) as compared to Saroglitazar. On the other hand, Fenofibrate (100 mg/kg) showed decrease in serum TG (54%), which was similar to Pioglitazone but had no significant effect on SBP. Overall, the results suggest that Saroglitazar, a drug approved in India for treatment of diabetic dyslipidemia shows insulin sensitizing, lipid lowering and blood pressure lowering effects in an animal model of metabolic syndrome.
693-P - Lipid Lowering Effects of Saroglitazar in Preclinical Models: Potential Synergistic Interaction with Statins, June 6, 2015
SURESH R. GIRI, AKSHYAYA RATH, BIBHUTI BHOI, CHITRANG TRIVEDI, PANKAJ R. PATEL, MUKUL R. JAIN, Ahmedabad, India
Disclosures
S.R. Giri: Employee; Author; Cadila Healthecare Limited. A. Rath: Employee; Author; Cadila Healthecare Limited. B. Bhoi: Employee; Author; Cadila Healthecare Limited. C. Trivedi: Employee; Author; Cadila Healthecare Limited. P.R. Patel: Employee; Author; Cadila Healthecare Limited. M.R. Jain: Employee; Author; Cadila Healthecare Limited.
Saroglitazar is a novel Dual PPARα/γ agonist that showed significant triglyceride-lowering and insulin-sensitizing effects in various preclinical models. In present study, we have evaluated the lipid lowering activity of saroglitazar in hApoB100/hCETP double transgenic mice, a model that exhibits human-like serum LDL-C and HDL-C profile. The effect of saroglitazar in combination with statins was evaluated in high-fat, high-cholesterol (HF-HC) diet-fed golden Syrian hamsters. Once-daily oral treatment of hApoB100/hCETP double transgenic mice with saroglitazar for 14 days resulted in dose-dependent reductions in serum LDL-C. The ED50 for LDL-C lowering effect was found to be 0.11 mg/kg. Once-daily oral treatment with Saroglitazar (1 mg/kg) for 14 days caused 67% reduction in LDL-C, 50% reduction in total cholesterol (TC), 39% reduction in triglycerides (TG) and 61% reduction in LDL-C/HDL-C ratio as compared to vehicle treated controls.The HF-HC diet-fed hamsters treated with saroglitazar (1 mg/kg), atorvastatin (0.62 mg/kg) and rosuvastatin (0.62 mg/kg) once daily for seven days did not show any reduction in LDL-C when these agents were administered alone. However, co-administration of saroglitazar (1 mg/kg) with atorvastatin (0.62 mg/kg) or rosuvastatin (0.62 mg/kg) showed a significant and synergistic LDL-C lowering effect (42 and 48% reduction respectively). Similar synergistic effect was also observed in case of serum triglycerides (42 and 53% reduction) and LDL-C/HDL-C ratio (43 and 49% reduction). Overall, these results suggest that Sarogltiazar is an effective therapeutic option for treatment of dyslipidemia, particularly in combination with statins .
1187-P - Effect of Saroglitazar on Fatty Acid Metabolism in Zucker Fa/Fa Rats, June 7, 2015
MAHMOUD ELAZZOUNY, NATHAN R. QI, MELANIE L. SCHMITT, ELIZABETH LIMBACK, SURESH GIRI, MUKUL R. JAIN, CHARLES F. BURANT, Ann Arbor, MI, Ahmedabad, India
Disclosures
M. ElAzzouny: None. N.R. Qi: None. M.L. Schmitt: None. E. Limback: None. S. Giri: Employee; Author; Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India. M.R. Jain: Employee; Author; Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India. C.F. Burant: Consultant; Author; Zydus Research Centre, Cadila Healthcare Limited, Ahmedabad, India.
Saroglitazar is a novel Dual PPARα/g agonist recently approved in India for the treatment of diabetic hypertriglyceridemia. To understand the mechanisms of action of saroglitazar in vivo, we treated Zucker fa/fa (n=10-12 in each group) with vehicle, fenofibrate (F) (150 mg/kg) or saroglitazar (Saro) (0.4 or 4 mg/kg/day) for 14 days. On day 15, rats were gavaged with 5ml/kg of corn oil which contained [U-13C]Palmitic Acid (PA) (1 gm/5ml). Plasma was obtained hourly for 8 hours. Adiopose and skeletal muscle was collected at 8 hours. Only 4 mg/kg/day Saro increased body weight (p < 0.01) and reduced fasting insulin (p= < 0.01 vs. vehicle) as well as reducing plasma triglyceride (TG) at 0 and 2 hour post corn oil treatment (p < 0.01 and p < 0.001, respectively). LC-MS and GC-MS were used to assess the incorporation of 13C-lipids into plasma and tissue lipids (n=5 for tissue metabolomics studies). The major M+16 isotopomers of the major TG species, TG(52:3) and TG(52:4), rose in the first two h following gavage (likely reflecting chylomicron production) and declined over the next 4 hours with a secondary rise at 6-8 h. In contrast, F-treatment caused a greater increase in M+16 TG species; both low and high dose Saro significantly attenuated the appearance of M+16 TG. In all animals, Major M+16 phosphatidyl choline PC(34:1), carried primarily in HDL and VLDL, rose at similar rates, however the % labeling in the F-treated animals was significantly lower, suggesting a reduction in liver derived lipids by F. Low and high dose Saro significantly increased the accumulation of M+16 palmitate in adipose tissue (by 86% and 247%, respectively, p < 0.01). F, low and high dose Saro decreased Gastrocnemeous M+16 palmitate labeling, which could be due to induction of lipid oxidation by F and potentially Saro and reduced plasma levels of TG in Saro. In conclusion, Saro significantly reduces fasting and postprandial TG levels through enhanced clearance of TG into adipose tissue and works by a mechanism distinct from that of F, a ‘pure’ PPARα activator.
134-LB - Efficacy of Exenatide-Saroglitazar Combination in Treatment of NAFLD in Type 2 Diabetes, June 7, 2015
KIRAN PAL. SINGH, MOHINISH CHHABRA, AVINAINDER SINGH, JYOTIKA MANAN, SHAKUN DABRA, Ajitgarh, India
Disclosures
K.P. Singh: None. M. Chhabra: None. A. Singh: None. J. Manan: None. S. Dabra: None.
Non Alcoholic Fatty Liver Disease (NAFLD) is commonly associated with T2DM. Current treatment is aimed at lifestyle modifications only. Recently, we studied the efficacy of a novel Dual PPAR agonist - Saroglitazar in reversing the biochemical manifestations of MetS. Recent evidence also suggests a role of Incretin based therapies for the management of NAFLD in diabetics. We set out to combine these two approaches for the management of NAFLD in diabetics. We studied the effects of Exenatide in combination with Saroglitazar on hepatic fat content and other biochemical parameters in obese diabetics with NAFLD. 40 patients on dietary, Metformin and statin therapy received treatment with exenatide alone (10 mcg BD) (n=20) or exenatide and saroglitazar (4mg PO) (n=20) for 24 weeks. Age, BMI, diabetes duration and abnormal transaminase levels were comparable between the two groups. Hepatic steatosis was measured by Transient Elastography (Fibroscan).Other parameters including BMI, FPG, PPPG, HbA1c, lipid profile, RFT and LFT were measured.
| PARAMETERS | GROUP-1 BASELINE (EXENATIDE ONLY) | GROUP-1 WEEK 24 | CHANGE GROUP 1 | GROUP-2 BASELINE (EXENATIDE+SAROGLITAZAR) | GROUP-2 WEEK 24 | CHANGE GROUP 2 | p VALUE (changes between groups) |
| HbA1c (%) | 7.9 +/- 0.54 | 7.09 +/- 0.29 | - 0.81 | 8.1 +/- 1.01 | 6.94 +/- 0.40 | - 1.16 | 0.09 (NS) |
| HDL-C (mg/dL) | 35.8 +/- 9.8 | 38.1 +/- 8.9 | + 6.4 % | 31.6 +/- 10.5 | 38.4 +/- 10.3 | + 21.5 % | 0.003 |
| TRIGLYCERIDES (mg/dL) | 362.9 +/- 167.2 | 233.8 +/- 60.8 | - 35.6 % | 390.4 +/- 96.6 | 180.3 +/- 51.6 | - 53.8 % | 0.01 |
| LIVER FAT CONTENT (dB/m) | 319.3 +/- 31.4 | 248.3 +/- 30.5 | - 22.2 % | 330.7 +/- 36.1 | 202.8 +/- 28.3 | - 38.7 % | <0.001 |
We conclude that the Exenatide-Saroglitazar combination leads to significant reductions in Liver fat content and serum triglycerides. It also raises HDL-C significantly in these patients. This combination maybe effective at retarding the progression of hepatic steatosis and longitudinal studies are required to look at the long term effects of this combination.
New Indian Drug Saroglitazar Targets 'Diabetic Dyslipidemia', May 16, 2015
Nashville, Tennessee — A novel glucose- and lipid-lowering drug that is currently available only in India demonstrated efficacy and safety in a 9-month multicenter post-marketing study.
The findings were presented May 15, 2015 here at the American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress
At 9 months, triglycerides were reduced by 44% (from 298 mg/dL at baseline to 156 mg/dL) and non-HDL cholesterol dropped by 30% (199 mg/dL to 132 mg/dL), both significant (P < .0001). Total cholesterol and LDL cholesterol were both significantly reduced, by 23% and 18.5%, respectively (both P < .0001) and there was statistically significant improvement in HDL-C from a mean of 41 mg/dL at baseline to 44.5 mg/dL at 9-month follow-up.
Average HbA1c levels, recorded for 695 patients, dropped from 8.5% at baseline to 7.0% at 9 months, also highly significant (P < .0001). Fasting plasma glucose levels were reduced by 28% (from 172 mg/dL to 117 mg/dL), and postprandial glucose values dropped by 35% (244.5 mg/dL to 149 mg/dL), again significant (P < .0001).
Body weight didn't change over the 9 months (mean (73.9 kg at baseline vs 72.4 kg at 9-month follow-up), and there were no serious drug-related adverse events.
Triglycerides, The ignored twin of cholesterol in Lipids
Times of India, Mumbai Edition, Thursday, February 5, 2015
Mumbai: If cholesterol is the don of lipids (LDL-low density lipoprotein) then triglycerides (TG) is his major domo. TGs are the end products of digestion and breakdown of a fatty meal. When you think of fat being stored in your hips and belly you’re thinking of TGs. This leaves a special place for HDL (high density lipoprotein) cholesterol which is the good component.
Whilst the white and black races are flooded with a surge of LDL cholesterol, there is a majority amongst the Indians who carry the increased triglyceride gene. TGs often abound more than the traditionally treacherous LDL and this, either isolated or when associated with low HDL, forms a typically lethal lipid pattern. Indeed it is a dangerous precursor for making the blood thick and leads to the deposition of fats within arteries.
If desirable levels are < 140mg/dl, abnormal patterns amongst such Indians range from 200-500 and some patients even exceed this. Unfortunately high sugars are known to accompany high TGs, so the poor diabetic takes a double hit. This deranged lipid pattern being genetic, is seen to persist even in second and third generation Indians, whose families migrated half a century ago, proving that it is not the environment or habits that incite this elevation.. Like cholesterol, eating of fatty foods definitely enhances TGs but interestingly even the intake of starchy products (rice, potatoes etc) can add to TGs.
Statins are the wonder antilipid agents. However, whilst they lower the other cholesterol components, their action on TGs is not that potent and a lot of patients have a residual surfeit of TGs despite taking optimum doses of statins. Heretofore unsuccessful in the quest for a drug to reduce TGs, a lot has been tried and tested. Fenofibrate, nicotinic acid, omega 3 acids etc are often used but have not attained the desired goal. A new group of compounds– the glitazaars are now seen as the best in tackling this lipid fraction successfully.
Proudly in this “make in India” age, Saroglitazar, (saaro in Gujrati means good) the first of this group to be invented and manufactured in Ahmedabad and made available in 2013, has displayed great potency in reducing TGs. As if God sent, it also mildly reduces sugar and thus has been seen to be extremely useful in the diabetic. Medically it is mandatory to reduce cardiovascular mortality from lipids especially in the diabetic who has his hands (blood??) full of potential risks.
You can take an Indian out of India but not India out of Indian so, the TGs-riddled Indian gene is important to recognize and treat early. To ensure accurate determination of TGs, a minimum eight-hour fasting is required. Prudent dietary measures can also assist in curbing it. Unlike cholesterol, TG burnout with brisk exercise is possible and should be co-opted.
So next time you think of fats, get the full picture, for in the underworld of lipids, often the “Khamoshiyan” of the TGs speak louder than cholesterol.
(Dr Hemant Thacker is a consultant physician & cardio-metabolic specialist attached to south Mumbai hospitals. (Email:dochpt@gmail.com)
DNA, September 16, 2014
After India success, Cadila to take innovator drug to US
Mumbai: Cadila Healthcare will soon start filings for approval of its innovator drug Lipaglyn in advanced markets such as the US and Europe.
The drug has garnered a patients base of 50,000 in India within the first year of its launch.
Ganesh Nayak, chief operating officer and executive director, Cadila Healthcare, told dna, "We launched Lipaglyn in the country on September 16 last year and we have till date 50,000 satisfied patients using the product. We have around 3,000 diabetologists, cardiologists and physicians. For us, this forms a good database. Now, we can take this product to the world."
Lipaglyn, to be used to treat diabetic dyslipidemia and hypertriglyceridemia in Type II diabetes, is the first new chemical entity (NCE) discovered and developed indigenously by an Indian pharma company. This drug has a unique dual action of working on both glycemic control and the lipid controls.
Nayak said the three biggest markets globally are the US, Europe and Japan. "We will simultaneously start filing in these markets and the regulatory process will start within the next few months. Within the next three to five years we would bring in our lipaglyn at the global level in terms of sales and marketing. Japan will take a little more time since there are some technical requirements in that market. Also to market in these places, we might look at different modules of selling this product there," he added.
In another development, Zydus Wellness, a subsidiary of the Ahmedabad-based Cadila Healthcare, recently launched a corporate social responsibility (CSR) initiative called 'Donate your Calories'.
This campaign has been initiated by Zydus Wellness' leading brand SugarFree (a low-calorie sugar substitute). The aim is to promote healthy eating and to save sugar calories by converting to a healthier choice, and the calories saved will then be donated to underprivileged children.
"This is a part of our CSR initiatives. We have tied up with an NGO called Akshaya Patra which feeds 14-15 lakh school children everyday. From "donate your calories", whatever will be the amount of calories saved will be donated to this NGO in terms of monetary proceeds. Initially, the initiative will be for a three-month period, that is, from October to December, and depending on its success we will review it. Our target is to save 300 crore of calories within these first three months," Nayak said.
Zydus pioneers a breakthrough with LIPAGLYN, India’s first NCE to reach the market
India, September 16, 2013
LipaglynTM - India’s first NCE launched in the market
Three months after announcing its breakthrough in research, the Zydus Group has launched LipaglynTM, a novel drug targeted at bridging an unmet healthcare need for treating Diabetic Dyslipidemia and Hypertriglyceridemia in type 2 diabetes, not controlled by statins alone. LipaglynTM will be available across India and can be prescribed by cardiologists, diabetologists and general physicians. The therapy is priced at Rs. 25.90 per tablet.
The therapy is marketed by Zydus Discovery, a new division launched to exclusively market the original research products of the group’s research pipeline, the first being LipaglynTM . With a strength of 200 people, the division also has regional medical advisors to support the scientific promotion of discovery research products. The launch of LipaglynTM begins with a series of CMEs and scientific symposia to highlight the gaps in the current management of diabetes and the unmet healthcare need of Diabetic Dyslipidemia.
Diabetic Dyslipidemia is a condition where a person is diabetic and has elevated levels of the triglycerides, a decrease in the "good" high-density lipoprotein (HDL) cholesterol and may have elevated levels of the "bad" low-density lipoprotein (LDL) cholesterol and total cholesterol concentration in the blood. Optimal LDL cholesterol levels for adults with diabetes are less than 100 mg/dL, optimal HDL cholesterol levels are equal to or greater than 40 mg/dL, and desirable triglycerides levels are less than 150 mg/dL. LipaglynTM , is the first therapy to be approved for this condition.
Speaking on the occasion, Mr. Pankaj R. Patel, Chairman and Managing Director, Zydus Group said, “It’s a great milestone for Indian pharmaceutical research today as LipaglynTM completes its journey from the lab to the market. LipaglynTM has opened up a new path in the care and management of diabetes and its complications and I believe this is just the beginning of India’s contribution to the world of pharma research.”
Research has shown that diabetes is one of the major risk factors of CVD. Globally, 3 out every 4 patients suffering from diabetes also suffer from dyslipidemia. India has a population of nearly 65 million diabetics and 77 million pre-diabetics and of this, an estimated 55 million people currently suffer from diabetic dyslipidemia. In dyslipidemia patients with diabetes, CV risk is heightened by 3-4 times as compared to people without diabetes. Hence, addressing the problem of diabetes and dyslipidemia is crucial in tackling the health risk posed by CVD.
Discovered by the Zydus Research Centre, the dedicated NCE research arm of the Zydus group, LipaglynTM is a best-in-class innovation. A team of 400 research scientists at ZRC designed a unique cellular mechanism of action following an extensive structure-activity relationship study.
As a Dual PPAR agonist, LipaglynTM has a predominant affinity to PPAR alpha and moderate affinity to PPAR gamma. This two-pronged, dual action helps in a reduction of triglycerides and LDL (bad) cholesterol, and an increase in HDL (good) cholesterol and also showed a reduction in Fasting Plasma Glucose and glycosylated haemoglobin (HbA1c), thereby confirming its beneficial effects of both lipid and glycemic control in diabetic patients. LipaglynTM has a superior safety profile. With a non-renal route of elimination, LipaglynTM has no adverse events like edema, weight gain, myopathies or derangement of liver and/or kidney functions, thus making it safe and efficacious. LipaglynTM is recommended for once daily administration as a 4 mg tablet.
Zydus Discovery will offer a dedicated LipaglynTM support programme to patients and caregivers. The programme shall provide counselling and support through toll-free helpline numbers and online support through its website www.Lipaglyn.com.
India, September 16, 2013
Editor’s synopsis:
- • LipaglynTM is the first Glitazar to be approved in the world and is the first NCE discovered and developed indigenously by an Indian Pharma Company
- • The drug has been approved for launch in India by the Drug Controller General of India (DCGI)
- • Over 80% of all diabetic patients are estimated to be suffering from diabetic dyslipidemia. There are more than 350 million diabetics globally – so the people suffering from diabetic dyslipidemia could be around 300 million
- • With 20 discovery research programmes under various stages of clinical development, the group invests over 7% of its turnover in research
- • At group’s state-of-the-art research arm, the Zydus Research Centre, over 400 research scientists are engaged in NCE research alone
The Zydus Group announced a breakthrough in its research efforts with LipaglynTM (Saroglitazar), a novel drug targeted at bridging an unmet healthcare need for treating Diabetic Dyslipidemia or Hypertriglyceridemia in type 2 diabetes, not controlled by statins alone. The drug has been approved for launch in India by the Drug Controller General of India (DCGI). With a novel action that offers lipid and glucose lowering effects in one molecule, LipaglynTM is the first Glitazar to be approved anywhere in the world.
“LipaglynTM provides patients suffering from diabetic dyslipidemia the option of a once-daily oral therapy that has a beneficial effect on both lipid parameters as well as glycemic control,” said Mr. Pankaj R. Patel, Chairman and Managing Director, Zydus Group. "It has always been our dream to take a molecule right from the concept stage up to its launch. Today, we have realized this dream. It is an important breakthrough and I would like to dedicate this to all the Indian research scientists in the field of drug discovery,” Mr. Patel added.
Diabetic Dyslipidemia is a condition where a person is diabetic and has elevated levels of the total cholesterol, the "bad" low-density lipoprotein (LDL) cholesterol and the triglycerides and a decrease in the "good" high-density lipoprotein (HDL) cholesterol concentration in the blood. Optimal LDL cholesterol levels for adults with diabetes are less than 100 mg/dL, optimal HDL cholesterol levels are equal to or greater than 40 mg/dL, and desirable triglycerides levels are less than 150 mg/dL. LipaglynTM , a non-thiazolidinedione, is the first therapy to be approved for this condition.
World over, it is estimated that 30% of all deaths occur due to cardiovascular diseases (CVD). In India, one out of every five persons is at serious risk of developing CVD. Research has shown that diabetes is one of the major risk factors of CVD. India has a population of nearly 65 million diabetics and 77 million pre-diabetics. 85 - 97% of the diabetes patients suffer from dyslipidemia or lipid abnormalities. Hence, addressing the problem of diabetes and dyslipidemia is crucial in tackling the health risk posed by CVD.
Discovered by the Zydus Research Centre, the dedicated NCE research arm of the Zydus group, LipaglynTM is a best-in-class innovation, designed to have a unique cellular mechanism of action following an extensive structure-activity relationship study initiated in the year 2000. LipaglynTM has a predominant affinity to PPAR alpha isoform and moderate affinity to PPAR gamma isoform of PPAR nuclear receptor subfamily. The molecule has shown beneficial effects on lipids and glycemic control without side effects. This molecule underwent extensive pre-clinical characterisation and the IND was submitted in the year 2004.
As a part of the clinical development programme, extensive Phase-I, Phase-II and Phase-III clinical trials were conducted to evaluate the phamacokinetics, pharmacodynamics, efficacy and safety of LipaglynTM. The new drug application for LipaglynTM was based on a comprehensive clinical development programme spanning eight years.
Results from the first Phase III programme with Pioglitazone as a comparator drug in diabetes patients showed that the 4 mg dose of LipaglynTM led to a reduction of triglycerides and LDL (bad) cholesterol, and an increase in HDL (good) cholesterol and also showed a reduction in Fasting Plasma Glucose and glycosylated haemoglobin (HbA1c) thereby confirming its beneficial effects of both lipid and glycemic control in diabetic patients.
In the second Phase III study, LipaglynTM was studied in diabetic dyslipidemic patients insufficiently controlled with statin therapy. The results from this study confirmed that LipaglynTM had a pronounced beneficial effect on both the lipid and glycemic parameters in these subjects.
In both the studies, LipaglynTM was well tolerated and had a better safety profile than the comparators. Importantly LipaglynTM has a non-renal route of elimination, and did not show adverse events like edema, weight gain, myopathies or derangement of liver and/or kidney functions, thus making it safe and efficacious. LipaglynTM is recommended for once daily administration as 4 mg tablets.
Zydus will offer a dedicated LipaglynTM support programme to patients and caregivers. The programme shall provide important support and information regarding access, adherence, education and thereby help patients to start and appropriately manage their disease and therapy over time.
About Zydus Group
Zydus Group is an innovative, global pharmaceutical company that discovers, develops, manufactures and markets a broad range of healthcare therapies. From a turnover of Rs. 250 crore in 1995, the group posted revenues of over Rs. 6300 crore in FY2013. With 20 discovery research programmes under various stages of clinical development, the group invests over 7% of its turnover in research. At the group’s state-of-the-art research arm, the Zydus Research Centre, over 400 research scientists are engaged in NCE research alone. The group employs over 15,000 people worldwide and is dedicated to creating healthier communities globally. It aims to be a leading global healthcare provider with a robust product pipeline; achieve sales of over $3 billion by 2015 and be a research-based pharmaceutical company by 2020.
For further information, please contact:
| Sujatha Rajesh / Rashmi Nair | Narayan Bhatt |
| Zydus Group | Adfactors PR |
| Cell: 09974051180 / 09724313237 | Cell: 09979915777 |
| sujatha.rajesh@zyduscadila.com; rashminair@zyduscadila.com |
narayan.bhatt@adfactorspr.com; |