Saroglitazar Cuts Blood Sugar More Than Dapagliflozin in Fatty Liver Study

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes saw meaningful improvements in liver fat, blood sugar control, and liver enzymes with both saroglitazar and dapagliflozin over 25 weeks of treatment, according to a prospective multicenter cohort study conducted at four diabetes specialty centers in Lucknow, Uttar Pradesh, India. The study, published in Health Science Reports, directly compared the two drugs in a real-world clinical setting where physicians chose which medication each patient received based on their individual needs.

The research team enrolled 54 adults aged 18 to 70 years, splitting them evenly between the two treatment arms with 27 patients in each group. All participants had MASLD or nonalcoholic fatty liver disease confirmed by vibration-controlled transient elastography, commonly known as FibroScan. Eligibility required either severe hepatic steatosis, defined as a controlled attenuation parameter (CAP) of at least 292 dB/m, or liver fibrosis of at least stage F2, indicated by a liver stiffness measurement (LSM) of 8.0 kPa or higher. Every participant also had type 2 diabetes and was receiving routine clinical care for glycemic management alongside the study medication.

Patients received either saroglitazar 4 mg or dapagliflozin 10 mg once daily for 25 weeks. The allocation was non-randomized, meaning physicians assigned treatments at their discretion rather than by chance. This design choice reflects real-world prescribing patterns but introduces potential selection bias, as clinicians may preferentially choose one drug over the other based on a patient’s specific metabolic profile. The study was prospectively registered with the Clinical Trials Registry of India and followed ethical guidelines including the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice standards.

The primary endpoint was the change from baseline in liver steatosis and fibrosis scores as measured by FibroScan after 25 weeks. Secondary endpoints included changes in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid parameters such as triglycerides and high-density lipoprotein cholesterol, and glycemic parameters including fasting plasma glucose, glycated hemoglobin (HbA1c), and the incidence of treatment-emergent adverse events.

Both drugs produced significant within-group reductions in CAP, indicating decreased hepatic steatosis. The dapagliflozin group saw CAP fall from a baseline of 310.22 ± 26.09 dB/m to 287.04 ± 39.89 dB/m, a mean change of −23.19 dB/m (p = 0.001). The saroglitazar group experienced a larger numerical drop from 314.70 ± 23.11 dB/m to 278.67 ± 38.55 dB/m, a mean change of −36.04 dB/m (p < 0.0001). However, the between-group difference in CAP reduction did not reach statistical significance (p = 0.44), meaning the study cannot conclude that either agent is superior for reducing hepatic fat.

Liver stiffness measurements declined in both groups but did not achieve statistical significance within either arm. The dapagliflozin group showed a mean LSM change of −0.46 kPa (p = 0.114), while the saroglitazar group showed −0.96 kPa (p = 0.384). The between-group difference at Week 25 was also non-significant (p = 0.80). The authors note that substantial fibrosis regression typically requires at least 52 weeks of therapy in most pharmacologic trials, making the 25-week duration potentially too brief to capture meaningful antifibrotic effects.

Glycemic control improved significantly in both groups, but saroglitazar demonstrated a notably greater effect. HbA1c fell by −1.52% in the saroglitazar arm (from 8.28% ± 2.02% to 6.76% ± 0.96%, p < 0.0001) compared with −0.84% in the dapagliflozin arm (from 8.14% ± 1.65% to 7.30% ± 0.94%, p = 0.0145). At Week 25, the between-group comparison showed HbA1c was significantly lower with saroglitazar (6.76% ± 0.96% vs. 7.30% ± 0.94%, p = 0.04). An analysis of covariance adjusting for baseline values confirmed this difference remained significant (adjusted difference −0.55%, 95% CI −1.05 to −0.05, p = 0.033), addressing the baseline imbalance between groups.

Changes in fasting and postprandial plasma glucose were modest and did not reach statistical significance in either group. Triglyceride levels decreased significantly with both therapies, with a numerically greater reduction in the saroglitazar group (−62.48 mg/dL vs. −28.27 mg/dL), though the between-group difference was not statistically significant (p = 0.21). HDL-cholesterol changes were small and non-significant in both arms. Liver enzymes declined significantly in both treatment groups, with saroglitazar producing a larger absolute ALT reduction (−30.51 U/L vs. −8.65 U/L), though baseline ALT was significantly higher in the saroglitazar group (66.73 ± 47.45 U/L vs. 42.85 ± 22.82 U/L, p = 0.022), indicating greater hepatocellular injury at enrollment. By Week 25, ALT and AST concentrations were similar between groups.

No complications such as hypoglycemia, gastrointestinal symptoms, hepatic decompensation, ketoacidosis, edema, or any treatment-related adverse events were reported in either treatment arm on active questioning at each visit. The authors specifically probed for edema and fluid retention given saroglitazar’s PPAR-γ component, which raises a theoretical risk of these effects seen with conventional PPAR-γ agonists. The absence of edema in this study is consistent with prior evidence that saroglitazar, unlike conventional PPAR-γ agonists, is largely devoid of pedal edema and weight gain at approved doses.

The study has several limitations. As a non-randomized, open-label design, it is vulnerable to selection and observational biases. The baseline ALT imbalance suggests underlying clinical variability that likely reflects real-world prescribing behavior, where clinicians preferentially select saroglitazar for patients with more pronounced metabolic derangements. With only 54 participants, the study was not statistically powered, limiting the precision of estimates and the ability to detect smaller between-group effect sizes. The 25-week duration may be too brief to assess long-term disease effects, and no histological confirmation was possible. Serum adiponectin was not measured, so the extent to which saroglitazar’s glycemic benefit is mediated by adiponectin induction could not be assessed. The authors call for larger, longer, randomized trials to confirm whether either agent confers a true hepatic advantage in MASLD management.

Subject of Research: Comparative efficacy of saroglitazar and dapagliflozin on hepatic steatosis and glycemic control in MASLD patients with type 2 diabetes

Article Title: Comparative Efficacy and Safety of Saroglitazar and Dapagliflozin on Hepatic Steatosis and Glycemic Control in Patients With Metabolic Dysfunction‐Associated Steatotic Liver Disease: A 25‐Week Prospective Multicenter Comparative Cohort Study

Article References: Gupta, M., Chandra, K. P., Awasthi, R., Pande, A. R., Gupta, N. R., Agarwal, V., & Kumar, D. (2026). Comparative Efficacy and Safety of Saroglitazar and Dapagliflozin on Hepatic Steatosis and Glycemic Control in Patients With Metabolic Dysfunction‐Associated Steatotic Liver Disease: A 25‐Week Prospective Multicenter Comparative Cohort Study. Endocrinology, Diabetes & Metabolism, 9(6), Article e70377. https://doi.org/10.1002/edm2.70377

Image Credits: AI Generated

DOI: 10.1002/edm2.70377

Keywords: MASLD, saroglitazar, dapagliflozin, hepatic steatosis, HbA1c, FibroScan, type 2 diabetes, liver fibrosis, PPAR agonist, SGLT2 inhibitor, liver enzymes, triglycerides