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/12
*Illustrative chart

10. Published Sept 2013
Clinical Drug Investigation

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

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

14. 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

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

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

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

18. Phase 3: PRESS VI
Lipaglyn Vs Placebo: Adverse events

19. 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.

20. *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.

21. THANK
YOU