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LIPAGLYN
(Saroglitazar)
for
DIABETIC DYSLIPIDEMIA
Dr. T. Vijay bhushanam
M.B.B.S, M.D
Objectives
• Diabetic dyslipidemia
– Components
– Complications
– Treatment
– Need for novel treatment
• LIPAGLYN (Sarogli...
Diabetic dyslipidemia
Components
1. High Tryglycerides
2. Low HDL-c
3. Postprandial lipemia
Diabetic dyslipidemia
Complications
Hyperglycemia:
– Macrovascular complications:
• CVD
– Microvascular complications:
• R...
Diabetic dyslipidemia
Treatment and Benefits
• Glycemic control
– Microvascular benefits: Well proven
– Macrovascular bene...
Diabetic dyslipidemia
What is needed in the management
• Treating both Hyperglycemia and dyslipidemia is the
comprehensive...
Diabetes. 2005 Aug;54(8):2460-70
Diabetic dyslipidemia
What is needed in the management
Dual PPAR-α/γ agonists
LIPAGLYN – Saroglitazar
World’s first approved dual PPAR-α/γ agonist
Spectrum of PPAR activity of various
agents : Each PPAR agonist is unique
Adapted from -
http://www.theheart.org/documents...
Published Sept 2013
Clinical Drug Investigation
Phase 3: PRESS V
Lipaglyn vs Pioglitazone in Diabetic
dyslipidemia
11
Phase 3: PRESS V
Lipaglyn Vs Pioglitazone: Safety assessment
13
Pai V et al. J Diabetes Sci Technol 16 Jan 2014
Critical Parameters Benefits
Weight Gain • There was no increase in the weight in Lipaglyn
group,
• However Pioglitazone h...
Phase 3: PRESS VI
Lipaglyn Vs Placebo in
Diabetic dyslipidemia on Atorvastatin
15
Phase 3: PRESS VI
Lipaglyn Vs Placebo: Results
Primary Efficacy end point: TG reduction
Effect on other lab parameters
Phase 3: PRESS VI
Lipaglyn Vs Placebo: Safety assessment
Phase 3: PRESS VI
Lipaglyn Vs Placebo: Adverse events
Summary
• Current standards of care for blood glucose, blood pressure
and LDL-C leaves behind a high level of residual vas...
*The above values are as per International Standards Regular monitoring of blood sugars at home with the help of a
glucome...
THANK
YOU
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SAROGLITAZAR (LIPAGLYN)

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Saroglitazar, Lipaglyn

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  • There is significant and independent association between atherogenic dyslipidaemia components and microvascular complications, specifically diabetic kidney disease.*
  • PPARα is found in the liver, kidney, heart, skeletal muscle and vasculature, is implicated in the uptake and oxidation of fatty acids and lipoprotein metabolism.PPARgamma is mainly expressed in adipose tissue with lower expression detected in a wide range of differing tissues like spleen, intestine, pancreas, colon, kidney, skeletal muscle and macrophages. PPARγ agonists have beneficial effects on glucose homeostasis by increasing insulin sensitivity and glucose disposal and prevent the loss of beta cell mass in the pancreas. Fibrates are PPARα agonist used for triglyceride lowering in clinics and PPAR gamma agonists, Rosiglitazone and Pioglitazone are proven to be efficacious as insulin sensitizing agents for the treatment of type 2 diabetes.
  • Saroglitazar is the world’s first approved dual PPAR-α/γ agonist for diabetic Dyslipidemia.The journey of Saroglitazar from concept to market started in 2001, and went through various phase 1, 2, 3 studies and finally received market authorization this year.5000-10000 compounds synthesized, 250 goes for animal testing, 5 for human trial, 1 becomes drug Cost of development of 1 NCE - ~1.3 Bn USD
  • Let us look at the spectrum of PPAR activity of various agents. At one end rosiglitazoine which is a pure PPAR gamma agonist whereas on the other extreme fenofibrate, a pure PPAR alpha agonist. Lipaglyn is a predominantly PPARα agonist with optimal  PPARγ agonistic activity
  • Phase I study already published in Sept 2013 issue of Clinical Drug Investigation
  • Hence Lipaglyn has not got deleterious effect on weight, has proven cardiovascular safety, and has no potential for DILI, Renal injury, muscle toxicity or hemodilution.
  • Coming to the results of primary endpoint of PRESS VISaroglitazar 4mg produced 139.5mg/dL or 46-47% decrease in TG levels as compared to 78mg/dL or 24.9% decrease seen in atorva plus placebo arm. Saroglitazar reduces glycemic parametersIt reduced the non HDL levels by 32.5% at 4 mg dose
  • No significant changes seen in LFT or RFT or Body weight
  • Safety analysis: Both doses of saroglitazar were well tolerated. There were similar numbers of adverse events (AEs) in the saroglitazar and placebo arms. Most of the AEs were not related to treatment and were mild to moderate in intensity. AEs reported by two or more subjects in the study are presented in Table 5.
  • Transcript of "SAROGLITAZAR (LIPAGLYN)"

    1. 1. LIPAGLYN (Saroglitazar) for DIABETIC DYSLIPIDEMIA Dr. T. Vijay bhushanam M.B.B.S, M.D
    2. 2. Objectives • Diabetic dyslipidemia – Components – Complications – Treatment – Need for novel treatment • LIPAGLYN (Saroglitazar) – Mechanism of action – Clinical trials. • Summary
    3. 3. Diabetic dyslipidemia Components 1. High Tryglycerides 2. Low HDL-c 3. Postprandial lipemia
    4. 4. Diabetic dyslipidemia Complications Hyperglycemia: – Macrovascular complications: • CVD – Microvascular complications: • Retinopathy, Nephropathy, Neuropathy Dyslipidemia: – Macrovascular complications • Hypertriglyceridemia in T2DM patients increases the CV risk by 3 times. – Microvascular complications • Hypertriglyceridemia in T2DM patients increases the risk of diabetic kidney disease by 2-folds.* * Sacks FM, Hermans MP, Fioretto P et al. Association between plasma triglycerides and HDL-cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes: A global case-control study in 13 countries. Circulation 2013 Dec 18.
    5. 5. Diabetic dyslipidemia Treatment and Benefits • Glycemic control – Microvascular benefits: Well proven – Macrovascular benefits : Proven • PPAR-γ agonists: – Microvascular benefits : Well proven – Macrovascular benefits : Reduce CV end points (Death, MI, stroke) significantly (by 16-18%) in DM patients * • PPAR-α agonists: – Microvascular benefits : Prevent progression of early-stage diabetic retinopathy** – Macrovascular benefits : Proven ** * PROactive study. JA Dormandy et al, Lancet 2005; 366: 1279–89. Lincoff et al. JAMA 2007;298:1180-1188 ** FIELD study. Lancet 2007;370:1687-97. ACCORD Eye Study Group. New Engl J Med 2010;363:233-44. Fenofibrate: a new treatment for diabetic retinopathy. Molecular mechanisms and future perspectives. Curr Med Chem 2013; 20:3258-66.
    6. 6. Diabetic dyslipidemia What is needed in the management • Treating both Hyperglycemia and dyslipidemia is the comprehensive management of Diabetic dyslipidemia • Statins are the first line drugs for diabetic dyslipidemia, but still a significant proportion of residual risk (≈75%) remains, requiring add on therapies • PPAR agonists (α and γ) have hypolipidemic and antihyperglycemic effects with proven macro- and micro-vascular benefits, but there are concerns for safety
    7. 7. Diabetes. 2005 Aug;54(8):2460-70 Diabetic dyslipidemia What is needed in the management Dual PPAR-α/γ agonists
    8. 8. LIPAGLYN – Saroglitazar World’s first approved dual PPAR-α/γ agonist
    9. 9. Spectrum of PPAR activity of various agents : Each PPAR agonist is unique Adapted from - http://www.theheart.org/documents/sitestructure/en/content/programs/12 *Illustrative chart
    10. 10. Published Sept 2013 Clinical Drug Investigation
    11. 11. Phase 3: PRESS V Lipaglyn vs Pioglitazone in Diabetic dyslipidemia 11
    12. 12. Phase 3: PRESS V Lipaglyn Vs Pioglitazone: Safety assessment 13 Pai V et al. J Diabetes Sci Technol 16 Jan 2014
    13. 13. Critical Parameters Benefits Weight Gain • There was no increase in the weight in Lipaglyn group, • However Pioglitazone has shown an average increase of 1.6 kg Cardiovascular safety  2D Echo and ECG Examinations  No change in cardiac function  No edema observed Safety and Tolerance Lipaglyn demonstrated no significant change in : • LFT : (No DILI) • RFT: (Creatinine / eGFR) • CPK • Hemoglobin Phase 3: PRESS V Lipaglyn Vs Pioglitazone: Advantages
    14. 14. Phase 3: PRESS VI Lipaglyn Vs Placebo in Diabetic dyslipidemia on Atorvastatin 15
    15. 15. Phase 3: PRESS VI Lipaglyn Vs Placebo: Results Primary Efficacy end point: TG reduction Effect on other lab parameters
    16. 16. Phase 3: PRESS VI Lipaglyn Vs Placebo: Safety assessment
    17. 17. Phase 3: PRESS VI Lipaglyn Vs Placebo: Adverse events
    18. 18. Summary • Current standards of care for blood glucose, blood pressure and LDL-C leaves behind a high level of residual vascular risk, including microvascular and macrovascular complications. • Statin therapy alone is not sufficient for all-at risk patients (AACE response to AHA/ACC 2013 cholesterol guidelines) • Targeting Diabetic dyslipidaemia (High TG, High Non- HDL, Low HDL) with non statin therapies is required along with statins. • LIPAGLYN is the best available option with Hypolipidemic and Antihyperglycemic effects (↓TG, ↓Non-HDL, ↓HbA1C) and insulin sensitizing actions.
    19. 19. *The above values are as per International Standards Regular monitoring of blood sugars at home with the help of a glucometer is recommended and also maintenance of a SMBG (Self Monitoring of Blood Glucose) chart, which should be showed to your Diabetologist during every visit.
    20. 20. THANK YOU
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