SAROGLITAZAR (LIPAGLYN)

Saroglitazar, Lipaglyn

1. LIPAGLYN (Saroglitazar) for DIABETIC DYSLIPIDEMIA Dr. T. Vijay bhushanam M.B.B.S, M.D

2. Objectives Diabetic dyslipidemia Components Complications Treatment Need for novel treatment LIPAGLYN (Saroglitazar) Mechanism of action Clinical trials. Summary

3. Diabetic dyslipidemia Components 1. High Tryglycerides 2. Low HDL-c 3. Postprandial lipemia

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. 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. 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. Diabetes. 2005 Aug;54(8):2460-70 Diabetic dyslipidemia What is needed in the management Dual PPAR- α / γ agonists

8. LIPAGLYN – Saroglitazar World’s first approved dual PPAR- α / γ agonist

9. Spectrum of PPAR activity of various agents : Each PPAR agonist is unique Adapted from - http://www.theheart.org/documents/sitestructure/en/content/programs/1228135/1228135.html *Illustrative chart

10. Published Sept 2013 Clinical Drug Investigation

11. Phase 3: PRESS V Lipaglyn vs Pioglitazone in Diabetic dyslipidemia 11

12. Phase 3: PRESS V Lipaglyn Vs Pioglitazone: Safety assessment 13 Pai V et al. J Diabetes Sci Technol 16 Jan 2014

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. Phase 3: PRESS VI Lipaglyn Vs Placebo in Diabetic dyslipidemia on Atorvastatin 15

15. Phase 3: PRESS VI Lipaglyn Vs Placebo: Results Primary Efficacy end point: TG reduction Effect on other lab parameters

16. Phase 3: PRESS VI Lipaglyn Vs Placebo: Safety assessment

17. 4_84 Phase 3: PRESS VI Lipaglyn Vs Placebo: Adverse events

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. *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.

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