Vol 11, No 5 (2022)
Research paper
Published online: 2022-09-30

open access

Page views 7177
Article views/downloads 969
Get Citation

Connect on Social Media

Connect on Social Media

Long Term Safety and Efficacy of Saroglitazar in Indian Patients with Diabetic Dyslipidemia and Very High Triglyceride Levels: Real World Evidence

Arjun Baidya1
Clin Diabetol 2022;11(5):316-320.

Abstract

Objective: Diabetes and diabetic dyslipidemia with high triglycerides (TGs) are commonly associated. Saroglitazar is the first dual PPAR α/γ agonist approved in India for the management of diabetic dyslipidemia. The objective of this observational study was to assess the long-term safety and efficacy of saroglitazar in patients with diabetic dyslipidemia with very high triglycerides (> 500 mg/dL). Materials and methods: This was a single-center, retrospective observational study which was conducted among 150 patients with type 2 diabetes who had diabetic dyslipidemia with hypertriglyceridemia (> 500 mg/dL at baseline). All patients were on saroglitazar 4 mg once daily and all had complete follow-up data. At baseline, all patients were on stable doses of antidiabetic and statin therapy. Results: Significant reduction of TG and LDL-cholesterol was observed from baseline to 12th week: from 669.93 ± 81.22 to 268.72 ± 82.32 mg/dL and from 167.68 ± 10.881 to 118.88 ± 12.16 mg/dL (p < 0.0001 and < 0.001), respectively. The mean HbA1c was reduced from 8.02 ± 0.3 to 7.71 ± 0.5% (< 0.001). This reduction in lipid and glycemic parameters continued till 52th week. At 52 weeks mean TG, LDL-cholesterol and HbA1c were reduced to 221.51 ± 61.81 mg/dL, 118.88 ± 12.16 mg/dL and 7.12 ± 0.2 % (p <0.001 for all). No major adverse event was reported during the study period. Creatine phosphokinase (CPK), liver enzymes and creatinine did not alter significantly. Conclusions: Long term use of saroglitazar leads to significant improvement in both glycemic and lipid parameters in patients with diabetic dyslipidemia with very high triglycerides (>500 mg/dl) and initially not controlled by statins alone. Therefore, to fulfil the unmet need, long-term use of saroglitazar could be an effective, well tolerated and safe option.

RESEARCH PAPER

ISSN 2450–7458
e-ISSN 2450–8187

Long Term Safety and Efficacy of Saroglitazar in Indian Patients with Diabetic Dyslipidemia and Very High Triglyceride Levels: Real World Evidence

Arjun Baidya
Department of Endocrinology and Metabolism, Nil Ratan Sircar Medical College, Kolkata, India

Address for correspondence:

Dr. Arjun Baidya

Associate Professor

Department of Endocrinology and Metabolism

Nil Ratan Sircar Medical College

138 AJC Bose Road, Kolkata 700014, India

e-mail: arjun.baidya@gmail.com

Clinical Diabetology 2022, 11; 5: 316–320

DOI: 10.5603/DK.a2022.0039

Received: 28.04.2021 Accepted: 28.09.2021

ABSTRACT

Objective: Diabetes and diabetic dyslipidemia with high triglycerides (TGs) are commonly associated. Saroglitazar is the first dual PPAR α/γ agonist approved in India for the management of diabetic dyslipidemia. The objective of this observational study was to assess the long-term safety and efficacy of saroglitazar in patients with diabetic dyslipidemia with very high triglycerides (> 500 mg/dL).

Materials and methods: This was a single-center, retrospective observational study which was conducted among 150 patients with type 2 diabetes who had diabetic dyslipidemia with hypertriglyceridemia (> 500 mg/dL at baseline). All patients were on saroglitazar 4 mg once daily and all had complete follow-up data. At baseline, all patients were on stable doses of antidiabetic and statin therapy.

Results: Significant reduction of TG and LDL-cholesterol was observed from baseline to 12th week: from 669.93 ± 81.22 to 268.72 ± 82.32 mg/dL and from 167.68 ± 10.881 to 118.88 ± 12.16 mg/dL (p < 0.0001 and < 0.001), respectively. The mean HbA1c was reduced from 8.02 ± 0.3 to 7.71 ± 0.5% (< 0.001). This reduction in lipid and glycemic parameters continued till 52th week. At 52 weeks mean TG, LDL-cholesterol and HbA1c were reduced to 221.51 ± 61.81 mg/dL, 118.88 ± 12.16 mg/dL and 7.12 ± 0.2 % (p <0.001 for all). No major adverse event was reported during the study period. Creatine phosphokinase (CPK), liver enzymes and creatinine did not alter significantly.

Conclusions: Long term use of saroglitazar leads to significant improvement in both glycemic and lipid parameters in patients with diabetic dyslipidemia with very high triglycerides (>500 mg/dl) and initially not controlled by statins alone. Therefore, to fulfil the unmet need, long-term use of saroglitazar could be an effective, well tolerated and safe option. (Clin Diabetol 2022, 11; 5: 316–320)

Keywords: saroglitazar, high triglyceride, type 2 diabetes, dyslipidemia

Introduction

Dyslipidemia is one of the major concerns for people with diabetes and 75% of patients with diabetes have associated dyslipidemia [1]. The burden of cardiovascular diseases (CVDs) is greatly influenced by diabetic dyslipidemia (DD) and considered as one of the major contributing risk factors [2]. Another name of diabetic dyslipidemia is atherogenic dyslipidemia, which is a triad of high triglycerides (TG) and small dense low-density lipoprotein cholesterol (sd-LDL-C), and low high-density lipoprotein cholesterol (HDL-C) [3]. Worldwide, the most common cause of mortality is CVDs and the magnitude of this burden is growing rapidly [4]. As per INTERHEART study, among the 9 easily measured risk factors that account for over 90% of the risk of acute myocardial infarction (AMI), which include dyslipidemia, diabetes, hypertension, obesity, diet, smoking, alcohol consumption, physical activity and psychosocial factors, the strongest risk predictor of AMI is dyslipidemia [5]. Hypertriglyceridemia is one of the major risk factors of pancreatitis and it accounts for 1 to 4% of all cases of acute pancreatitis. When the triglyceride level is more than 500 mg/dL it can cause pancreatitis, but it becomes clinically significant when triglyceride levels are >1000 mg/dL [6–8]. When metabolic syndrome is treated and various components of dyslipidemia, especially triglycerides, are lowered, the rate of coronary events is reduced. High doses of omega-3 fatty acids and fibrates are drugs of choice for the initiation of pharmacological treatment after lifestyle modification. When hypertriglyceridemia is accompanied by elevated low-density lipoprotein levels, 3-hydroxy-3 methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are preferred. In patients with hypertriglyceridemia who have low HDL levels, extended release niacin can be considered.

The function of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), which is mainly expressed in skeletal muscle, heart and liver, is to regulate fatty acid oxidation and ketone body synthesis. On the other hand, PPAR-gamma promotes triglyceride storage and differentiation of preadipocytes into adipocytes [9] and is present in lower intestine and adipose tissue. The only approved dual PPAR a/g agonist for the treatment of diabetic dyslipidemia in India is saroglitazar. It has a positive effect on insulin sensitivity as well as a reducing effect on elevated TG. Addition of saroglitazar to statin led to a significant reduction in non-HDL cholesterol (−32.5%) and TG (−46.7%) in multiple randomized clinical trials [10, 11]. In patients with diabetic dyslipidemia, treatment with saroglitazar effectively reduces small-dense low-density lipoprotein (sd-LDL), non-high- -density lipoprotein cholesterol (non-HDL-C) particles and triglycerides along with blood glucose level [12]. The present observational study was done to evaluate the long-term safety and efficacy of saroglitazar in Indian DD patients in real-world scenario.

Materials and methods

The present study is a single-center, retrospective observational study which was conducted among type 2 diabetes patients who were also diagnosed with diabetic dyslipidemia along with hypertriglyceridemia. The inclusion criteria of the study were patients with type 2 diabetes aged >18 years and having high triglycerides (> 500 mg/dL) and on antidiabetic drugs and statins. The exclusion criteria for the present study were type 1 diabetes mellitus, moderate or severe liver and kidney disease, patients receiving fenofibrate and pioglitazone within previous 3 months, documented heart failure (NYHA class III or IV) and having any type of malignancy. As the lipid parameters of the participants were not controlled with statin alone, saroglitazar 4 mg was added as add-on therapy as per the approved indication by DCGI (Drugs Controller General of India). Pre-designed questionnaires were used to collect data of patients who visited the clinic from January 2014 to November 2018 and had been prescribed saroglitazar.

Initially, 164 patients with documented hypolipidemic and antidiabetic medication history and who were prescribed saroglitazar 4 mg tablet once daily before breakfast at baseline were selected for this study. Finally, data of 150 patients were selected after excluding 4 patients who did not have proper antidiabetic medication history and 10 patients who didn’t continue saroglitazar beyond 3 months. For each patient the analysis was done for three visits including at baseline, 3 months and 12 months. Glycemic parameters for the analysis were fasting plasma glucose, post-prandial plasma glucose and glycated hemoglobin (HbA1c); and lipid parameters were low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C). Pathological test reports of NABL (National Accreditation Board for Testing and Calibration Laboratories), accredited laboratories preferred by patients, were considered for the analysis. The LDL-C values and non-HDL-C were measured by direct method.

To compare the demographic and baseline disease characteristics descriptive statistics was used. For continuous variables data were presented as mean ± SD, median, percentiles or range and for categorical variables percentage was calculated. For homogeneity testing data from all the patients were compared at baseline using ANOVA test for continuous variables and Chi-square test or Fisher’s exact test for categorical variable. For statistical analysis, SAS 9.3 were used and 0.05 was set as significance level for all statistical tests.

Results

One hundred fifty patients who received saroglitazar 4 mg once daily and continued for 12 months were included in the analysis. The mean age of the patients was 57.6 (± 8.1) years and 61.3% of the patients were male. Average duration of diabetes was 7.8 (± 2.4) years. The patients had a mean weight of 71.3 (± 10.35) kg and a mean body mass index of 26.8 (± 3.89) kg/m2. A history of smoking and alcoholism were present in 14.6% and 2.6% patients, respectively (Tab. 1). In this study, all the of patients were on statin therapy at baseline, with atorvastatin being the most commonly used statin (59.4%) (Tab. 1). All patients were advised to continue on-going statin therapy and saroglitazar 4 mg once daily was prescribed as 2nd line lipid-lowering agent. Of the 150 patients, 5.3% was on single antidiabetic therapy, 31.3% was on dual antidiabetic therapy and 63.3% was on more than two antidiabetic drugs (Tab. 1). In the study population, the most commonly reported antidiabetic drug at baseline was metformin in 96.6% of the patients, followed by sulfonylureas in 60.6%, dipeptidyl peptidase-4 (DPP4) inhibitors in 54.3%, alpha glucosidase inhibitors in 15.3%, insulin in 12.0%, sodium-glucose cotransporter-2 (SGLT2) inhibitor in 8.6%, hydroxychloroquine in 7.3%, glucagon-like peptide 1 (GLP1) agonist in 1.3% (Tab. 1).

Table 1. Demographic Parameters and Pattern of Glucose Lowering Drugs and Statin Therapy at Baseline (n = 150)

Parameter

Baseline value

Age [years]

57.6 ± 8.1

Male (%)

92 (61.3%)

Weight [kg]

71.3 ± 10.35

BMI

26.8 ± 3.89

Duration of diabetes [years]

7.8 ± 2.4

Smokers (%)

22 (14.6%)

Alcoholic (%)

4 (2.6%)

Single antidiabetic drug

8 (5.3%)

Dual antidiabetic therapy

47 (31.3%)

More than two antidiabetic drugs

95 (63.3%)

Atorvastatin

89 (59.4%)

Rosuvastatin

61 (40.7%)

Metformin

145 (96.6%)

Sulfonylurea

91 (60.6%)

DPP4 inhibitor

68 (45.3%)

SGLT2 inhibitor

13 (8.6%)

Alpha glucosidase inhibitors

23 (15.3%)

Insulin

18 (12%)

Hydroxychloroquine

11 (7.3%)

GLP1 agonist

2 (1.3%)

BMI — body mass index; DPP4 — dipeptidyl peptidase-4; GLP1 — glucagon-like peptide-1; SGLT2 — sodium-glucose cotransporter-2

Saroglitazar in addition to oral antidiabetic medication and statin therapy showed significant improvement in all lipid and glycemic parameters at 12-week follow up and that improvement continued till 52 weeks. The mean TG was 669.93 ± 81.22 mg/dL vs. 221.51 ± 61.81 mg/dL at baseline and 52-week follow-up, a significant reduction of 66.9% from baseline. A statistically significant change in all other lipid parameters was also noted (Fig. 1). A mean reduction of 38.47% in LDL-C levels, 52.62% in non-HDL-C levels, 44.84% in total cholesterol levels and mean increase of 4.72% in HDL-C levels was noted. Analysis of glycemic parameters revealed a statistically significant 11.22% reduction (0.9% point absolute reduction) in HbA1c from baseline value of 8.02% to 7.12% at 12-month follow-up. A significant reduction in fasting and post-prandial plasma glucose level of 25.47 and 108.44 mg/dL respectively from a mean baseline of 160.52 and 269.62 mg/dL, respectively (Tab. 2). Saroglitazar administration did not lead to weight gain. No serious adverse events were reported by the patients (Tab. 3).

LDL-C — low-density lipoprotein cholesterol; non-HDL-C — non high-density lipoprotein cholesterol; TG — triglycerides
Table 3. Total Number of Adverse Events (AE) at the End of the Study

Type of AE

Visit 1 (12th week)

Visit 2 (52nd week)

Overall

15 (10%)

18 (12%)

Asthenia

2 (1%)

1 (0%)

Muscle pain

11 (7%)

8 (5%)

Dizziness

0

1 (0%)

Gastrointestinal

12 (8%)

9 (6%)

Hypoglycemia

2 (1%)

9 (6%)

Weight gain

1 (0%)

2 (1%)

Table 2. Changes in Lipid Parameters and HbA1c Level

Parameter

Baseline (week 0)

12th week

P

52nd week

P

Triglycerides [mg/dL]

669.93 ± 81.22

268.72 ± 82.32

0.0001

221.51 ± 61.81

0.001

Total cholesterol [mg/dL]

310.2 ± 33.04

240.7 ± 23.41

0.001

171.1 ± 21.82

0.001

Non-HDL-C [mg/dL]

270.8 ± 34.08

198.6 ± 28.02

0.001

128.3 ± 27.69

0.001

LDL-C [mg/dL]

167.68 ± 10.881

118.88 ± 12.16

0.001

103.17 ± 5.51

0.001

HDL-C [mg/dL]

40.42 ± 5.87

41.16 ± 6.13

0.059

42.33 ± 5.79

0.02

HbA1c [%]

8.02 ± 0.3

7.71 ± 0.5

0.001

7.12 ± 0.2

0.001

FPG [mg/dL]

160.52 ± 7.23

132.47 ± 5.81

0.001

119.62 ± 4.11

0.001

PPG [mg/dL]

269.62 ± 24.39

174.16 ± 16.31

0.001

161.18 ± 16.91

0.001

SGOT [U/L]

42.15 ± 3.18

41.14 ± 3.5

0.21

40.11 ± 3.4

0.31

SGPT [U/L]

37.34 ± 4.5

37.34 ± 4.5

0.23

36.32 ± 4.7

0.21

Serum creatinine [mg/dL]

0.7 ± 0.24

0.7 ± 0.22

0.53

0.7 ± 0.19

0.51

CPK [U/L]

76.3 ± 19.4

71.8 ± 24.2

0.62

65.3 ± 18.1

0.51

Discussion

The present study highlights the added benefit of saroglitazar when combined with statin and clearly points out that this combination has significant and marked advantage in improving all the lipid parameters. A statistically significant reduction in total cholesterol of 44.84 %, triglycerides of 66.9%, non-HDL-C of 52.62% and LDL-C of 38.47% was observed at the end of 52 weeks. When added to existing baseline antidiabetic medications, a statistical significant improvement in glycemic parameters was also observed, including 0.9% absolute reduction in HbA1c and improvement in both fasting and post prandial plasma glucose. In this study no serious adverse event which required medical attention were observed. There were no weight gain or edema and not any alteration in liver enzymes or serum creatinine were observed at the end of the study.

An associated low HDL-C and a higher triglycerides were observed in Indians as compared to Caucasians [13, 14]. Among major risk factors of cardiovascular disease (CVD), higher triglycerides were always considered as a strong one and recent advances has clearly mentioned that increase in CVD diseases were directly associated with higher TG levels. In a recent observational study of 34 years with more than 75,000 subjects from general population, it was observed that lower TG level was associated with lower CV risk. The group with TG < 90 mg/dL had 60% lower risk (statistically significant) of ischemic heart diseases than those with TG 360 mg/dL [15]. Another meta-analysis published in 2014 revealed that non-fasting TG of 600 mg/dL versus 72 mg/dL was associated with hazard ratio of 5.1 (95% CI 3.5−7.2) for myocardial infarction, 3.2 (2.5−4.1) for ischemic heart disease, 3.2 (2.2−4.7) for ischemic stroke, and 2.2 (1.8−2.7) for all-cause mortality [16]. Thus, higher TG level is found to be associated with increased cardiovascular risk. Although a few patients can develop pancreatitis with triglyceride levels > 500 mg/dL, the risk for pancreatitis is clinically significant when triglyceride levels are > 1000 mg/dL [6−8].

For the management of dyslipidemia, as per the 2020 American Diabetic Association guidelines, statin is recommended as primary therapy [17]. Even after statin therapy residual cardiovascular risk remains one of the major concern and it is postulated that atherogenic diabetic dyslipidemia is a major factor. A novel molecule, saroglitazar, is a dual PPAR α/γ agonist, approved for the management of DD in India.

In a recently conducted 24-week study with saroglitazar, researchers observed a significant decrease in non-HDL-C, sd-LDL-C, HbA1c from baseline: 142.3 ± 59.3 mg/dL to 109.9 ± 45.5 mg/dL; 32.5 ± 11.3 mg/dL to 25.9 ± 11.8 mg/dL and 8.1 ± 1.7 (%) to 6.9 ± 0.7 (%) and a significant increase in HDL-C from baseline: 37.3 ± ± 18.4 mg/dL to 43.4 ± 15.6 mg/dL [18]. In another large observational study of saroglitazar in 2804 patients with diabetic dyslipidemia, researchers observed a significant decrease in TG from 312.3 ± 122.7 mg/dL to 188.7 ± 61.4 mg/dL; non-HDL-C from 201.8 ± ± 64.1 mg/dL to149.4 ± 41.0 mg/ dL; HbA1c from 8.3 ± ± 1.3 (%) to 7.4 ± 0.9 (%); and significant increase in HDL-C from 38.8 ± 8.7 mg/dL to 41.0 ± 7.1 mg/dL after 12 weeks [12].

In a post marketing surveillance study of saroglitazar in 18 patients with type 2 diabetes with severe hypertriglyceridemia (baseline TG ≥ 1000 mg/dL), authors has observed a significant decrease in TG (baseline: 1265.9 ± 394.3 mg/dL to week-12: 402.0 ± 221.8 mg/dL), non-HDL-C (baseline: 320.8 ± 172.8 mg/dL to week-12: 176.4 ± 62.9 mg/dL), and HbA1c [baseline: 8.9 ± 1.7 (%) to week-12: 7.8 ± 0.9 (%)] [19]. In a 58-week observational study of saroglitazar in 158 patients with diabetic dyslipidemia (baseline TG ≥ 150 mg/dL), authors found significant reduction in TG (baseline: 319.9 ± 178.8 mg/dL to week-58: 174.0 ± 113.6 mg/dL), non-HDL-C (baseline: 140.1 ± 55.4 mg/dL to week-58: 104.5 ± 49.7 mg/dL), and HbA1c [baseline: 7.9 ± 1.5 (%) to week-58: 7.3 ± 1.4 (%)] [20].

Limitations

This is a retrospective observational study, so medication compliance cannot be ascertained. The specific assigned laboratory was not used to conduct the pathological test. The sample size was small.

Conclusions

A significant improvement was observed in both glycemic and lipid parameters in patients with diabetic dyslipidemia having very high triglycerides (> 500 mg/dL) who were treated with saroglitazar ٤ mg once daily for ٥٢ weeks. Saroglitazar was well tolerated and no serious adverse event was reported throughout the study period. Randomized, controlled clinical trials with longer duration of follow up in this group of patients are needed.

Funding

No funding or sponsorship was received for this study or the publication of this article.

Conflict of interest

None declared.

References

  1. Selby JV, Peng T, Karter AJ, et al. High rates of co-occurrence of hypertension, elevated low-density lipoprotein cholesterol, and diabetes mellitus in a large managed care population. Am J Manag Care. 2004; 10(2): 163–170, indexed in Pubmed: 15005509.
  2. Mooradian AD, Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009; 5(3): 150–159, doi: 10.1038/ncpendmet1066, indexed in Pubmed: 19229235.
  3. Musunuru K. Atherogenic dyslipidemia: cardiovascular risk and dietary intervention. Lipids. 2010; 45(10): 907–914, doi: 10.1007/s11745-010-3408-1, indexed in Pubmed: 20524075.
  4. World Health Organization. (2011). Global status report on noncommunicable diseases 2010. World Health Organization. https://apps.who.int/iris/handle/10665/44579 (27.04.2021).
  5. Yusuf S, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. The Lancet. 2004; 364(9438): 937–952, doi: 10.1016/s0140-6736(04)17018-9.
  6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the third report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA. 2001; 285(19): 2486–2497, doi: 10.1001/jama.285.19.2486, indexed in Pubmed: 11368702.
  7. Athyros VG, Giouleme OI, Nikolaidis NL, et al. Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. J Clin Gastroenterol. 2002; 34(4): 472–475, doi: 10.1097/00004836-200204000-00020, indexed in Pubmed: 11907366.
  8. DiMagno EP, Chari S. Acute ancreatitis. In: Feldman M, Friedman LS, Sleisenger LH. ed. Sleisenger & Fordtran’s gastrointestinal and liver disease. W B Saunders, St. Louis (MO) 2002: 913–942.
  9. Chatterjee S, Majumder A, Ray S. Observational study of effects of Saroglitazar on glycaemic and lipid parameters on Indian patients with type 2 diabetes. Sci Rep. 2015; 5: 7706, doi: 10.1038/srep07706, indexed in Pubmed: 25573251.
  10. Jani RH, Pai V, Jha P, et al. A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI). Diabetes Technol Ther. 2014; 16(2): 63–71, doi: 10.1089/dia.2013.0253, indexed in Pubmed: 24138536.
  11. Pai V, Paneerselvam A, Mukhopadhyay S, et al. A Multicenter, Prospective, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Saroglitazar 2 and 4 mg Compared to Pioglitazone 45 mg in Diabetic Dyslipidemia (PRESS V). J Diabetes Sci Technol. 2014; 8(1): 132–141, doi: 10.1177/1932296813518680, indexed in Pubmed: 24876549.
  12. Kaul U, Arambam P, Kachru R, et al. A Prospective, Multicentre, Single Arm Clinical Study to Evaluate the Effect of saroglitazar on NonHigh-Density Lipoprotein Cholesterol in Patients with Diabetic Dyslipidemia Inadequately Controlled with Diet, Exercise, and Statin-The GLIDDER Study. J Diabetes Metab. 2019; 10: 2(819): 1–8, doi: 10:819. doi: 10.35248/215.
  13. Joshi SR, Anjana RM, Deepa M, et al. ICMR-INDIAB Collaborative Study Group. Prevalence of dyslipidemia in urban and rural India: the ICMR-INDIAB study. PLoS One. 2014; 9(5): e96808, doi: 10.1371/journal.pone.0096808, indexed in Pubmed: 24817067.
  14. 20th Annual Convention of the American Association of Physicians of Indian Origin Clinical Implications: Dyslipidemia in the Asian Indian Population June 29, 2002. https://southasianheartcenter.org/docs/AAPImonograph.pdf (27.04.2021).
  15. Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG, et al. Loss-offunction mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014; 371(1): 32–41, doi: 10.1056/NEJMoa1308027, indexed in Pubmed: 24941082.
  16. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014; 384(9943): 626–635, doi: 10.1016/S0140-6736(14)61177-6, indexed in Pubmed: 25131982.
  17. American Diabetes Association. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2020. Diabetes Care. 2019; 43(Supplement_1): S111–S134, doi: 10.2337/dc20-s010, indexed in Pubmed: 31862753.
  18. Shetty SR, Kumar S, Mathur RP, et al. Observational study to evaluate the safety and efficacy of saroglitazar in Indian diabetic dyslipidemia patients. Indian Heart J. 2015; 67(1): 23–26, doi: 10.1016/j.ihj.2015.02.007, indexed in Pubmed: 25820046.
  19. Joshi S, Vadgama J, Mody P, et al. Abstract #1224 Saroglitazar in the Treatment of Severe Hypertriglyceridemia in Patients with Type 2 Diabetes. Endocrine Practice. 2018; 24(supp. 1): 318, doi: 10.1016/S1530-891X(20)47516-0.
  20. Chatterjee S. Obser vational Study of Saroglitazar on Metabolic Parameters in Indian Patients with Diabetic Dyslipidaemia — A Fifty Eight Weeks of Clinical Experience. Diabetes & Obesity International Journal. 2018; 3(2), doi: 10.23880/doij-16000180.