Saroglitazar 58 Weeks Study

AUCTORES Journal of Diabetes and Islet Biology
Globalize Your research Sanjay Chatterjee, J Diabetes and Islet Biology
Open Access Mini Review
Real Time Clinical Safety and Effectiveness of Long Term Use of Saroglitazar in
Indian Patients with Diabetic Dyslipidemia Having Abnormal Metabolic
Parameters
Sanjay Chatterjee 1*, Majumder A 2, Ray S 1 and Bhattacharjee K 3.
1
Apollo Gleneagles Hospital, Kolkata, India.
2
KPC Medical College, Kolkata, India.
3
PhD Scholar, JJT University, India.
*Corresponding Author : Sanjay Chatterjee, MD Consultant Diabetologist, Apollo Gleneagles Hospital, Kolkata, India.
Email: Sanjay_doc@yahoo.co.in
Received date: December 07, 2018;Accepted date : December 21, 2018; Published date: December 27, 2018.
Citation : Sanjay Chatterjee, Real Time Clinical Safety and Effectiveness of Long Term Use of Saroglitazar in Indian Patients with Diabetic Dyslipidemia
Having Abnormal Metabolic Parameters. J Diabetes and Islet Biology. Doi: http://dx.doi.org/ 10.31579/ jdib.18/003.
Copyright : © 2018 Sanjay Chatterjee. This is an open-access article distributed under the terms of The Creative Commons Attribution License,
whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Question: Indian patients with type 2 diabetes (T2DM) usually suffer At end of 58 weeks, metabolic parameters like TG, TC, LDL-C, FPG,
from multiple metabolic abnormalities, such as overweight, obesity, PPPG, HbA1c, non HDL-C were reduced significantly from baseline
high triglycerides (TG), low HDL-C, increased blood pressure, along (Table). Significant drop in non HDL-C may have beneficial impact on
with insulin resistance. In India, Saroglitazar is being used in the residual CV risk, while a reduction of both triglyceride and TG/HDL ratio
management of diabetic dyslipidemia since 2013. Randomized makes a shift of the small dense LDL particles to more buoyant and larger
controlled clinical trials of Saroglitazar (PRESS V & PRESS VI LDL particles which are less atherogenic.
studies) 1, 2 have established safety and efficacy of Saroglitazar in Regarding safety analysis, Saroglitazar was to be found safe without
T2DM patients with dyslipidemia. But the question is “What is the having any major/serious adverse events during 58 weeks of therapy.
real time clinical safety and effectiveness of Saroglitazar in Diabetic Liver enzymes ALT and AST were both reduced from baseline, the ALT
dyslipidemia, if it is used for more than a year? reduction at 58 weeks was found to be statistically significant (P<0.001).
Review scope: This article reviews the observational study and Serum creatinine level was not adversely affected during this
retrospective analysis of 58 weeks safety and effectiveness data of observational study. The change in body weight at 58 wees follow-up was
Saroglitazar in Indian patients having diabetic dyslipidemia [3]. found to be statistically significant (increased from 70.61 kg at baseline to
71.69 kg at 58 weeks; p=0.002) in this retrospective analysis.
Objective of this review: Phase III randomized controlled clinical
trials of Saroglitazar have evaluated the safety and efficacy of this Parameters Baseline At Follow-Mean Differe P value
drug for 12-24 weeks follow-up [1, 2]. Previously published post- values up change nce (%)
marketing studies evaluating the clinical safety and effectiveness of FPG (mg/dL) 160.5 134.7 -25.8 -16.0 <0.001
Saroglitazar in diabetic dyslipidemia had a shorter duration of follow- PPPG (mg/dL) 235..4 191.6 - 43.9 -18.6 <0.001
up (less than 1 year) [4-6]. We conducted a retrospective analysis of HbA1c (%) 7.91 7.25 - 0.65 - <0.001
safety and effectiveness data of Saroglitazar 4 mg once daily in Indian Cholesterol (mg/dL) 181.02 148.4 - 32.6 -18.0 <0.001
patients with T2DM, having metabolic abnormalities (like high TG Triglycerides (mg/dL) 319.9 174.0 - 145.8 -45.6 <0.001
and low HDL). This analysis included the data from the patients with HDL-C (mg/dL) 38.3 38.6 0.2 0.5 0.69
a mean follow-up duration of 58 weeks [3]. The main objective of this LDL-C (mg/dL) 102.0 90.5 - 11.5 -11.0 0.016
retrospective analysis was to evaluate long-term safety and Non HDL-C (mg/dL) 140.1 104.5 - 35.6 -25.4 <0.001
effectiveness of Saroglitazar in diabetic dyslipidemia. TG/HDL-C (mg/dL) 7.4 4.2 -3.2 -43.2 <0.001
Methods: We identified 158 patients having type 2 diabetes and Table.1: Metabolic Parameters: % Changes from baseline at 58 weeks
dyslipidemia (TG >150 mg/dl) who had been prescribed Saroglitazar 4 follow-up
mg once daily as per the prescribing information and the follow-up HDL-C: High density lipid cholesterol, LDL-C: Low density lipid
results were available for 58 weeks duration. Data of only those cholesterol, TG: Triglyceride, FPG: Fasting plasma glucose, PPPG: Post-
patients were considered for final evaluation having both baseline and prandial plasma glucose, HbA1c: glycated hemoglobin
follow-up values of fasting plasma glucose (FPG), post-prandial
plasma glucose (PPPG), glycated hemoglobin (HbA1c) and lipid Conclusion:
profile. Descriptive data analytics has been carried out in the present High TG is considerably associated with diabetes mellitus and it is of
study and were analyzed by appropriate statistical tests. A p value of utmost importance to reduce TG when it is more than >200 mg/dl. The
<0.05 was considered as statistically significant. results of this analysis showed that 58 weeks use of Saroglitazar
significantly improves the metabolic abnormalities (lipids and glycemic
Results: A total of 158 patients’ data was analyzed in this
parameters) in Indian diabetic patients with good safety and tolerability
observational study with variable co-morbidities and all were T2DM
profile.
patients, with high TG (TG>150 mg/dl). A total of 53.16% patients
were overweight/ obese and 58.86% patients were hypertensive. After Commentary
58 weeks, the mean blood pressure was significantly reduced, both Various recently published large observational and epidemiological
systolic (-4 mmhg, P= 0.004) and diastolic (-2 mmhg, P=0.001). studies have strongly established the positive association of High TG
(>150 mg/dl) with elevated CV risk [7-9].
Auctores Publishing – Volume1-003 www.auctoresonline.org Page - 01
J Diabetes and Islet Biology
The results from 22 year follow-up of the Bezafibrate Infarction References

Prevention (BIP) study and registry showed that in patients with
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by 68% [7]. The results from Strong Heart Study established that in to Evaluate the Safety and Efficacy of Saroglitazar 2 and 4 mg
American Indian patients with high TG (>150 mg/dL), Diabetes and Compared to Pioglitazone 45 mg in Diabetic Dyslipidemia (PRESS
low HDL had 54% increased risk of CHD and 2.13 times higher risk V). J Diabetes Sci Technol 8(1): 132-141.
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values [8]. So management of high TG is important and as per multicenter, prospective, randomized, double-blind study to evaluate
guidelines recommendations, statins are first line therapy while non- the safety and efficacy of Saroglitazar 2 and 4 mg compared with
statin TG lowering therapies (Saroglitazar, Fibrates, Niacin, Omega-3 placebo in type 2 diabetes mellitus patients having
fatty acid) may be considered as add on therapy only in those high risk hypertriglyceridemia not controlled with atorvastatin therapy (PRESS
patients who do not achieve their lipid targets (TG and non HDL-C) in VI). Diabetes Technol Ther 16(2): 63-71.
spite of optimal statin therapy. 3. Chatterjee S (2018) Observational Study of Saroglitazar on Metabolic
Parameters in Indian Patients with Diabetic Dyslipidaemia – A Fifty
Studies have also established that even mild to moderate elevation of
Eight Weeks of Clinical Experience. Diabetes Obes Int J, 3(2):
TG levels are associated with significant increase in the risk of acute 000180.
pancreatitis [10]. The latest consensus statement by American 4. Shetty SR, Kumar S, Mathur RP, Sharma KH, Jaiswal AD (2015)
Association of Clinical Endocrinologists and American College of
Observational study to evaluate the safety and efficacy of saroglitazar
Endocrinology (AACE/ACE) advocates reducing triglyceride levels
in Indian diabetic dyslipidemia patients. Indian heart journal 67(1):
when severely elevated (>500 mg/dL) to prevent pancreatitis [11].
23-26.
Saroglitazar is a dual PPAR α and γ agonist approved in India for the 5. Chatterjee S, Majumder A, Ray S (2015) Observational Study of
treatment of hypertriglyceridemia in patients with T2DM uncontrolled Effects of Saroglitazar on Glycaemic and Lipid Parameters on Indian
with statin therapy. In two phase 3 trials, Saroglitazar 4 mg once daily Patients with Type 2 Diabetes. Sci Rep 5: 7706.
showed significant decrease in triglyceride levels (-45 to 46.7%), non 6. Chatterjee S, Majumder A, Ray S (2016) Effect of Saroglitazar on
HDL-C (-32.5%) and HbA1c (-0.3%) with better safety and Metabolic Parameters in Indian Patients with Diabetic Dyslipidemia:
tolerability profile over the period of 12-24 weeks follow-up[1, 2]. In A 40-Week, Retrospective Analysis. Diabetes 65: A541-A556.
one Indian post-marketing, observational study, at 3 months follow- 7. Klempfner R, Erez A, Sagit BZ, Goldenberg I, Fisman E et al (2016)
up, Saroglitazar 4 mg led to significant reduction in TG (-35.8%), Elevated Triglyceride Level Is Independently Associated With
LDL-C (-16.4%), total cholesterol (-19%), non HDL-C (-23.4%) and Increased All-Cause Mortality in Patients With Established Coronary
significant 0.9% absolute reduction in HbA1c (As an add on to anti- Heart Disease Twenty-Two–Year Follow-Up of the Bezafibrate
diabetic medications) with no serious adverse events reported [4]. Infarction Prevention Study and Registry. Circ Cardiovasc Qual
A part of Chatterjee S et al 2018 study of 158 patients with follow-up Outcomes 9(2): 100-108.
of 58 weeks is a continuation of earlier published data with follow-up 8. Lee JS, Chang PY, Zhang Y, Kizer JR, Best LG et al (2017)
data of only 34 patients for a period of 14 weeks [3, 5]. In 58 weeks Triglyceride and HDL-C Dyslipidemia and Risks of Coronary Heart
follow-up study, it was observed that Saroglitazar 4 mg significantly Disease and Ischemic Stroke by Glycemic Dysregulations Status. The
improves various metabolic parameters (lipid and glycemic Strong Heart Study. Diabetes Care 40(4): 529-537.
parameters) along with favorable effects on serum ALT level and no 9. Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-
significant change in serum creatinine level. These 58 weeks follow- Hansen A (2014) Loss-of-function mutations in APOC3 and risk of
up results are in consistent with previous 14 weeks and 40 weeks ischemic vascular disease. N Engl J Med;371:32-41.
observational data analysis [5, 6]. Unlike previous observations (of no 10. Pedersen SB, Langsted A, Nordestgaard BG (2016) Non fasting
weight gain associated with Saroglitazar), in this study with much Mild-to-Moderate Hypertriglyceridemia and Risk of Acute
longer duration, the weight-gain has reached a level of statistical Pancreatitis. JAMA Intern Med 176(12): 1834-1842.
significance. However, it should be noted that many patients were on 11. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT
sulfonylureas and/or insulin, which are known to cause weight gain; et al (2017) Consensus Statement by the American Association of
hence the weight-gain cannot be solely attributable to Saroglitazar Clinical Endocrinologists and American College of Endocrinology on
alone. the Comprehensive Type 2 Diabetes Management Algorithm - 2017
Unique strength of this study is long duration of therapy of 58 weeks Executive Summary. Endocr Pract 23(2): 207-238.
but lack of vigilance of control group and small sample size (158
patients) are limitations of it. Larger and more comprehensive
randomized controlled clinical trials are required to establish and
further validate these findings.
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AUCTORES Journal of Diabetes and Islet Biology

Globalize Your research Sanjay Chatterjee, J Diabetes and Islet Biology

Open Access Mini Review

The results from 22 year follow-up of the Bezafibrate Infarction References

Auctores Publishing – Volume1-003 www.auctoresonline.org Page - 02

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