A Prospective, Multicentre, Single Arm Clinical Study to Evaluate the Effect of Saroglitazar on Non High-Density Lipoprotein Cholesterol in Patients with Diabetic Dyslipidemia Inadequately Controlled with Diet, Exercise, and Statin-The GLIDDER Study

Abstract

Objective: Diabetic dyslipidemia is highly atherogenic as it is associated with high triglyceride (TG), high small dense low-density lipoprotein (sd-LDL) particles and low High-Density Lipoprotein Cholesterol (HDL-C). Saroglitazar, a dual peroxisome proliferator activated receptor agonist (predominant PPAR-α agonist and modest PPAR-γ agonist), is approved in India for the management of diabetic dyslipidemia. The GLIDDER study was done to evaluate the effects of Saroglitazar 4 mg on non HDL-C as the primary endpoint and sd-LDL particles as a secondary endpoint in diabetic patients with dyslipidemia. Methods: This study was a 24 weeks, prospective, multicentre, single arm study conducted in 104 patients with diabetic dyslipidemia (TG ≥ 200 mg/dL) inadequately controlled with diet, exercise, and statins. It was conducted from April 2015 to November 2017 at three Indian centres. All the selected patients were given Saroglitazar 4 mg once daily before breakfast for 24 weeks. Efficacy evaluations of non HDL-C (calculated as Total Cholesterol (TC) minus HDL-C) (primary endpoint) and other lipid parameters (sd-LDL particles, TC, TG, HDL-C) and glycemic parameters (glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG)) were conducted after 24 weeks and compared to the baseline levels. Results: Total 104 patients (22% female) with mean age of 59.1 ± 11.4 years were enrolled in this study. In the perprotocol population, there was a significant reduction in non HDL-C (from 142.3 ± 59.3 mg/dL (baseline) to 109.9 ± 45.5 mg/dL (week-24); p<0.0001) and sd-LDL (from 32.5 ± 11.3 mg/dL (baseline) to 25.9 ± 11.8 mg/dL (week-24); p<0.0001). There was a significant reduction in TG, TC, HbA1c, and FPG with a significant increase in HDL-C at week-24 from baseline levels (p<0.05). Conclusion: Saroglitazar effectively reduces non HDL-C and sd-LDL particles in patients with diabetic dyslipidemia.

New dual peroxisome proliferator activated receptor agonist—Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence

“…Kaul et al [21] was the first study to examine the effects of Saroglitazar on non-HDL-C as the primary endpoint and sd-LDL-C as a secondary endpoint in 104 patients with diabetic dyslipidemia. The authors observed significant decrease in non-HDL-C (baseline: 142.…”

“…Chatterjee et al [30] conducted a 58 weeks observation study of Saroglitazar in 158 patients with diabetic dyslipidemia (baseline TG ≥ 150 mg/dL). The authors found significant [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]: Group 1 (12 weeks): Shetty et al [13], Thacker et al [14], Joshi et al [15], Bhattacharyya et al [16]; Group 2 (24 weeks): Saboo et al [17], Joshi et al [18], Chhaya et al [19], Mohit et al [20], Kaul et al [21], Goyal et al [22]; Group 3 (27 weeks): Chatterjee et al [23]; Group 4 (36 weeks): Joshi et al [24]; Group 5 (40 weeks): Chatterjee et al [25]; Group 6 (52 weeks): Joshi et al [26], Aneja et al [27], Maheshwari et al [28], Chatterjee et al [29]; Group 7 (58 weeks): Chatterjee et al [30]. Mean non-HDL-C calculation: data not available for Thacker et al [14], Saboo et al [17], Joshi et al [18], Chhaya et al [19], Mohit et al [20], Goyal et al [22] reduction in TG (baseline: 319.9 ± 178.8 mg/dL to week-58: 174.0 ± 113.6 mg/dL...…”

“…In Phase-3 clinical trials, most frequently reported AEs (≥ 2% of patients) with Saroglitazar 4 mg use were asthenia, gastritis, dizziness, tremors in the PRESS V study and were gastritis and pain in the PRESS VI study [11,12]. In real world clinical studies, Kaul et al [21] reported hypoglycemia after first dosing to be Saroglitazar related AE.…”

“…In all included studies, Saroglitazar favourably modulates lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Saroglitazar 4 mg effectively reduced lipid parameters-TG, TC, LDL-C and non-HDL-C, glycemic parameter-HbA1c, and effectively increased lipid parameter-HDL-C in patients with diabetic dyslipidemia [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Saroglitazar has a potential to address the residual cardiovascular risk associated with high non-HDL-C, high TG, and low HDL-C in patients with diabetic dyslipidemia [7,8].…”

“…Chhaya et al [19] reported knee joint pain in 2 patients. Kaul et al [21] reported occasional chest discomfort/chest pain in 2 patients, burning sole in 1 patient, hypoglycemia after first dosing in 1 patient, and occasional suffocation in 1 patient. Kaul et al [21] found hypoglycemia after first dosing to be Saroglitazar related AE.…”