Table 2. Clinical studies on saroglitazar.
NAFLD, Non-alcoholic fatty liver disease; NASH, Non-alcoholic steatohepatitis; ALT, Alanine transaminase; AST, aspartate transaminase; TG, Triglycerides; TC, Total cholesterol; HDL, High-density lipoprotein; LDL, Low-density lipoprotein; LSM, Liver stiffness measurement; SWE, Sheer wave elastography, NA, Not available, BMI, Body mass index, DM, diabetes mellitus, MRI-PDFF, Magnetic resonance imaging proton density fat fraction; CAP, Controlled attenuation parameter; ALP, Alkaline phosphatase; VLDL, Very low-density lipoprotein, Hba1c: Glycosylated hemoglobin; HOMA-IR, Homeostatic model assessment for insulin resistance
| Authors, Year | Design | Arms | Population | Number of Patients | Follow-up | Key Demographics | Biochemical Changes | Safety |
| Padole et al. 2021 (India) [20] | Prospective | Single arm | NAFLD (No specifications) | 91 | 12 weeks | Mean age=45 (18–66), 81% males, BMI 29.3 (23.6–42.2), ALT:48 (13–164), LSM:6.7 (3.6–13.1) 308 (249–400) | Outcomes divided into those with/without weight loss (5%). Weight Loss Group: Decrease in ALT, AST, CAP, and LSM (P<0.05) for all no weightloss group: Significant decrease in ALT, AST but not in LSM or CAP | NA |
| Jaiswal et al. 2021 (India) [21] | Retrospective | Single arm | Non-diabetic NAFLD | 45 | 24 weeks | Mean age=46±8.20, 55% males, ALT 85.52±17.12, LSM:8.11±2.18, CAP365.84±56.22 | Does not account for weight loss decrease in ALT, AST, CAP, and LSM (P<0.05) for all | NA |
| Roy et al. 2021 (India) [22] | Retrospective | Single arm | NAFLD with DM and dyslipidemia | 10 | 36 weeks | Mean age=59.3 years, 70% males, BMI 25.21± 3.07, HbA1c 7.8±0.343, TG 298.2±35.75, ALT 64.7±15.56, SWE 1.837±0.0691 | Significant decrease in all parameters (p<0.05 for all) | NA |
| Rajesh et al. 2021 (India) [23] | Prospective | Single | NAFLD with DM | 85 | 12 weeks | Mean age 56.81 ±4.06 BMI 25.94 ±2.20 HBA1c 10.29 ±0.64 Triglycerides 359.89 ±5.46 HDL 49.20 ±3.08 SGPT 49.62 ±.31 LSM 9.68 ±0.30 | Significant decrease in FBS, HBA1c, TC, TG, and SGPT, Mean decrease in LSM 3.61±3.98 | No ADR |
| Goyal et al. 2020 (India) [24] | Prospective | Single | NAFLD with DD | 107 | 24 weeks | Mean age 50.4 ± 12.3 BMI 28.8 ± 4.2 HBA1c 7.2 ± 0.65 TC 209.8 ± 62.4 Triglycerides 326.4 ± 98.5 HDL 38.2 ± 8.1 SGPT 94 (47–122) LSM 8.4 (7.1–9.3) CAP 335 (281–392) | Significant decrease in FBS, HBA1c, TC, TG, SGPT, SGOT, CAP, and LSM | Minor adverse events reported were fatigue in 2.8% (n=3), nausea in 1.9% (n=2), and dyspepsia 1.9% (n=2) |
| Siddiqui et al. 2020 (Multicentric, USA) [7] | Prospective | Double-blind placebo-controlled | Biopsy-proven NASH with NAS>4 | 16 paients Saro 2 mg:n=6 Saro 4 mg:n=7 Placebo n=3 | 24 weeks | Mean age 52±14; 85% of males rest not provided | Change in NAS was not statistically different with 4 mg (-1.9±1.57, p=0.60) when compared with saroglitazar 2 mg group (-1.5±0.84, p=0.77) and placebo (-1.3±0.58). Significant improvement in ballooning from 1.2±0.41 to 0.3±0.52 at week 24 with saroglitazar 2 mg and from 1.3±0.49 to 0.4±0.53 with saroglitazar 4 mg. Significant reductions in TG, TC, sd-LDL-C, and LDL-C | N=2 Not related to drug |
| Gawrieh et al. 2021 (Multicentric, USA) [6] | Prospective | Double-blind randomized | NAFLD established either by imaging (ultrasound, CT, or MRI) or liver biopsy showing NASH or simple steatosis and ALT ≥ 50 U/L | Saroglitazar 1 mg, n=26 group, saroglitazar 2 mg, n=25 group, saroglitazar 4 mg, n=27 group, and placebo n=28 | 16 weeks | The mean % ↓ ALT at week 16 was -45.8% (5.7) with saroglitazar 4 mg versus 3.4% with placebo. Significant ↓ in LFC [4.1%), HOMA-IR (-1.3), TG (-5.3 mg/dL) (p<0.05 for all). A mean weight gain of 1.5 kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (p>0.05). | Diarrhea n=3 cough n=3 Abdominal pain n=2 Bronchitis n=2 | |
| Mitra et al. 2020 (India) [25] | Prospective | Single | T2DM and NAFLD documented by ultrasonography of the abdomen | N=30 | 24 weeks | 11 patients had fibrosis F3 grade (9.5-12.4 kPa), and 19 patients had a fibrosis F4 grade (≥12.5 kPa) | At the six-month changes were noted as (HbA1c) ↓ (8.14 ± 0.52% to 7.74 ± 0.53%) TG ↓ (179.4 ± 38.33 mg/dL to 112.33 ± 26.82 mg/dL) LSM↓ (13.933 ± 2.87 kPa to 8.503 ± 1.86 kPa ) P<0.05 for all | None |
| Chaudhuri et al. 2023 (India) [26] | Prospective | Single | Patients with NAFLD with elevated ALT levels along with liver stiffness value ≥6 kPa and/or liver steatosis CAP >290 dB/m | N=63 | 2-point follow-up analysis at 24 and 52 weeks | Mean age=49.1(±11.09), Mean BMI 27.2(±4,1), 46% DM, 27% dyslipedemic, mean LSM 8.5±3.9, mean CAP 320(±46) 11 patients had compensated cirrhosis | Significant ↓in LSM baseline: 11.03±7.19 kPa 24-week (9.29±6.39 kPa), 52-week 8.59±6.35 kPa. Significant ↓ in CAP, ALT, AST, HbA1c, LDL, TC, and TG levels | Pruritis in 1 Increase stool frequency in 1 |
| Siddiqui et al. 2023 (Multicentric) [27] | Prospective | Pooled data analysis from multicentric phase II/III trials (USA, India, and Mexico) | Histologically proven NASH NAFLD or confirmed on the basis of imaging (ultrasound, computed tomography scan, or magnetic resonance imaging) | N=221 Saroglitazar 130 Placebo 91 | 16-24 weeks | Mean age=47.9±10.6 years, 56.1% females, mean BMI 30.9 ±5.3kg/m2 (36), 2% hypertensive, 32.6% DM, 21.7% on statins | Significant improvement in lipid parameters TC (–17 mg/dL, 95% CI, –24 to 9), TG (–45 mg/dL, 95% CI, –60 to 31), LDL (–8 mg/dL, 95% CI, –15 to –1), VLDL-C(–8 mg/dL, –14 to –3), and c sdLDL-C (–10 mg/dL, –17 to –2) | NA |
| Siddiqui et al. 2023 (USA) [28] | Prospective | Phase 2, single-arm study | Post liver transplant NAFLD NAFLD defined as CAP ≥264 dB/m. Primary endpoint: Liver fat reduction on MRI-PDFF | N=15 | 24 weeks | Mean age=58±12 years, mean BMI 37.4±7.4 kg/m2, DM: 26%, dyslipedemia 26%, hypertension 93% | Significant ↓ in MRI-PDFF (10.3±10.5% at baseline to 8.1±7.6%). A relative 30% reduction from the baseline MRI-PDFF value was noted in 47% of patients. Reduction ALP emerged as a predictor of PDFF response | Fluctuations in eGFR in two patients, one splanchnic vein thrombosis not related to drug |
| Hajare et al. 2019 (India) [29] | Prospective | Single arm | NAFLD and dyslipidemia with or without type 2 diabetes mellitus | N=52 | 52 weeks | Mean age=45.88±11.66 years, 71.15% males, 28.8% DM, 17.3% hypertensive, mean BMI 27.84±5.97 kg/m2 | Significant ↓ALT (p<0.001), AST, (p<0.001), TG (p<0.001), LSM ↓12.33±9.99 to 9.62±4.53 9, p=0.01) | NA |