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

Abstract

Background: Saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India.

Methods: In this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study.

Results: In 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies.

Conclusion: Saroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

Keywords: Alanine aminotransferase; Diabetic dyslipidemia; Dual PPAR agonist; Glycosylated hemoglobin; Non-alcoholic fatty liver disease; Saroglitazar; Triglyceride.

Fig. 1

Study selection flowchart

Fig. 2

Mean change from baseline in triglyceride (a) and non-HDL-C (b). Non-HDL-C: Non-high-density lipoprotein cholesterol. Studies included [–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]

Fig. 3

Mean change from baseline in total cholesterol (a), HDL-C (b), and LDL-C (c). HDL-C: High-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol. Studies included [–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 total cholesterol calculation: data not available for Joshi et al. [15], Saboo et al. [17], Joshi et al. [18], Goyal et al. [22], Joshi et al. [24]. Mean HDL-C calculation: data not available for Joshi et al. [15], Saboo et al. [17], Joshi et al. [18], Chhaya et al. [19], Goyal et al. [22], Maheshwari et al. [28], Chatterjee et al. [29]. Mean LDL-C calculation: data not available for Joshi et al. [15], Saboo et al. [17], Joshi et al. [18], Goyal et al. [22], Aneja et al. [27]

Fig. 4

Mean change from baseline in HbA1c (a), ALT (b), and body weight (c). HbA1c: Glycosylated hemoglobin; ALT: alanine aminotransferase. Studies included [–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 ALT calculation: data available for Thacker et al. [14], Saboo et al. [17], Joshi et al. [18], Goyal et al. [22], Chatterjee et al. [23]; Chatterjee et al. [25]; Chatterjee et al. [30]. Mean body weight calculation: data available for Shetty et al. [13], Bhattacharyya et al. [16], Chhaya et al. [19], Mohit et al. [20], Kaul et al. [21], Chatterjee et al. [23], Joshi et al. [24], Chatterjee et al. [25], Chatterjee et al. [29], Chatterjee et al. [30]