1. INTRODUCTION
Worldwide, cases of nonalcoholic fatty liver disease (NAFLD) are increasing. By 2030, NAFLD is predicted to become the top reason for liver transplants worldwide, causing rising expenses for healthcare systems [1]. In this review, we adopt the terminology NAFLD and nonalcoholic steatohepatitis (NASH) to remain consistent with the included literature; these correspond to the recently adopted terms metabolic dysfunction–associated steatotic liver disease and Metabolic dysfunction-associated steatohepatitis (MASH), as proposed by an international consensus [2]. NAFLD encompasses a range of Liver conditions, from simple steatosis to NASH, which may advance to steatohepatitis with fibrosis and cirrhosis [3] (Fig. 1). Hepatic steatosis on its own is called NAFLD, while NASH refers to a worsened condition involving inflammation and liver cell damage (steatohepatitis). In NASH, pericellular fibrosis is usually present, potentially evolving into cirrhosis over time [4]. NAFLD is diagnosed in individuals with at least 5% of hepatocytes containing fatty deposits, determined through liver biopsy or imaging, in those who intake minimal to no alcohol and lack other underlying causes of fatty liver disease [5]. The buildup of triglycerides within liver cells, i.e., hepatic steatosis, is the marked characteristic of NAFLD. This buildup is closely associated with obesity and metabolic syndrome [6]. Currently, progress in therapies for chronic hepatitis B and C, alongside the growing rate of obesity and metabolic disorders like type 2 diabetes mellitus (T2DM) and hyperlipidemia, is linked with a significant increase in NAFLD cases. Recent global estimates (2024–2025) suggest that NAFLD affects nearly 30% of the general population, with prevalence reaching 38% in the US—an almost 50% increase over the last three decades. In patients with T2DM, the NAFLD prevalence increases to 55%–70%, pointing to its close relationship with metabolic dysfunction [7,8]. Unlike other chronic liver diseases, where the risk factors are either modifiable (e.g., alcohol consumption) or treatable with specific therapies (such as viral or autoimmune hepatitis), NAFLD is driven by multiple factors, including genetic predispositions, epigenetic modifications, environmental exposures, and clinical influences [9]. Various pharmacological agents, including those targeting diabetes, lipid disorders, and natural bile acid therapies, have been employed in the management of NAFLD; however, they exhibit significant limitations [10]. This leads to a range of clinical presentations, necessitating personalised therapeutic approaches. Resmetirom (Rezdiffra) and Semaglutide (Wegovy) received Food and Drug Administration (FDA) accelerated approval in March 2024 and August 2025, respectively, for the treatment of MASH with moderate to advanced fibrosis (F2–F3) [11,18]. A network meta-analysis on the comparative efficacy of diabetes medications on liver enzymes and fat fraction in patients with NAFLD reported four classes of diabetes medications [GLP1RAs, DPP4i, Sodium–glucose cotransporter 2 inhibitors (SGLT2is), and TZD] significantly improve liver enzymes and liver fat content (LFC) [8,12]. SGLT2i are a class of antidiabetic agents with an insulin-independent action [13]. In numerous trials, SGLT2i have shown effectiveness in lowering liver stiffness, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels, and LFC, thereby making them a leading candidate for NAFLD therapy [14]. Obeticholic acid (OCA), a semi-synthetic hydrophobic bile acid analogue that acts as a highly selective Farnesoid X receptor (FXR) agonist, with an activation potency matching that of the endogenous bile acid chenodeoxycholic acid (CDCA), but is 100 times more potent. The FDA approved OCA for primary biliary cholangitis on May 27, 2016 [15]. Despite the termination of the Sanyal et al. [16] study in 2023, recent pharmacokinetic and pharmacodynamic analyses demonstrate that OCA retains antifibrotic activity via FXR signalling, evidenced by suppression of the bile acid synthesis marker C4 and induction of fibroblast growth factor 19 in patients with advanced fibrosis and compensated cirrhosis [17]. This mechanistic consistency supports the continued investigation of OCA and related FXR agonists for fibrosis in NAFLD. The current review aims to systematically evaluate and compare the efficacy and safety of SGLT2i and OCA in NAFLD-related fibrosis. This expanded review provides a more comprehensive understanding of the safety and efficacy of SGLT2i and OCA in reducing liver fibrosis and resolving NAFLD. Although the initial research focuses on the nondiabetic population, the paucity of subgroup data in OCA trials leads to the necessity of including mixed cohorts.
 | Figure 1. Progression of nonalcoholic liver disease to end-stage liver disease. [Click here to view] |
2. MATERIALS AND METHODS
2.1. Study design and protocol
This systematic review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [19]. The significant heterogeneity across the studies included led to the adoption of qualitative methods, foregoing a meta-analysis. Our systematic review protocol was preregistered with PROSPERO (Registration No. CRD4202460943). These guiding principles directed both the design of our systematic review and the reporting of its findings, as detailed in Figure 2.
 | Figure 2. PRISMA 2020 flowchart. [Click here to view] |
2.2. Search strategy
An extensive literature search was carried out on the efficacy and safety of OCA and SGLT2i for treating NAFLD and liver fibrosis from January 2015 to August 2025 using major literature databases such as PubMed, Google Scholar, PubMed Central, Web of Science, Embase, and clinicaltrials.gov. The keywords and the Medical Subject Headings thesaurus were used to ensure we captured all pertinent studies. For the literature search, a set of chosen keywords was employed, such as “SGLT2 inhibitors”, “OCA”, “NAFLD”, “liver fibrosis”, “NAFLD”, and “NASH”.
2.3. Inclusion and exclusion criteria
Adults (≥18 years) with metabolic dysfunction-associated fatty liver disease (MAFLD)/NAFLD/NASH and liver fibrosis verified by histology, elastography, or validated biomarkers were included in full-text, peer-reviewed studies. Only Randomised controlled Trials were eligible designs, and the outcomes included safety, histological or biochemical alterations, and improvement in fibrosis.
Studies without fibrosis outcomes, case reports/series, reviews, abstracts, systematic reviews, meta-analyses, observational studies, patients with other chronic liver diseases or posttransplant patients, pediatric populations, and animal studies were all disqualified. Moreover, studies involving patients on antidiabetic drugs or undergoing other therapies that might conflict with NAFLD treatment were not included. In addition, articles not published in English are not included.
2.4. Data collection process
The studies included in this review were systematically analysed, and two independent researchers meticulously extracted the data. Following the literature search, the retrieved studies were imported into the Mendeley software to eliminate duplicates. The selection of eligible studies was then finalised through a thorough two-stage screening process that included an initial assessment of titles and abstracts and a full-text review. The extracted data includes the first author’s name with location, type of study design, sample size, gender, intervention group, control group, outcomes, and trial registry number. Whenever disagreement arose, a third researcher was consulted to mediate and secure consensus in the decision-making process.
2.5. Quality of evidence
The overall quality of evidence from the 16 included randomized controlled trials (RCTs), 11 on SGLT2 inhibitors and 5 on OCA, was determined using the Cochrane Risk of Bias (RoB) 2tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework [20,21]. We found that most trials had a low to moderate RoB, which included adequate randomisation, concealed allocation, and blinded assessment of outcomes. In the case of large-scale OCA studies [16,32,33] showed very high methodical rigour, which included central histological evaluation, but we noted that the smaller or open-label SGLT2i studies [30,31,34] had issues with respect to incomplete blinding and small sample size. Missing outcome data was a very minor issue in most studies (we saw attrition of less than 15% in most), and we did not find any select report issues when we checked in with trial registries. In total, no study was found to have a high RoB in any domain.
For the certainty of evidence, we used the GRADE approach, which ranged from high to low which was by outcome. Evidence reflected in Neuschwander-Tetri et al. [33], Younossi et al. [32], and Alam et al. [34] with moderate certainty suggested that OCA has a considerable effect on the improvement of histological fibrosis (RR 2.29, 95% CI 1.35–3.88). However, the degree of variation was moderate (I² = 64%) due to differences in dose and patient differences. There was low-certainty evidence for NASH resolution (RR 1.71, 95% CI 0.98–2.98) because the confidence intervals included the null. For SGLT2i, moderate-certainty evidence from Taha et al. [30] and Taheri et al. [31] showed a substantial reduction in LFC (SMD −0.41, 95% CI −0.73 to −0.09) and lost weight (MD −2.15 kg, 95% CI −3.85 to −0.45), and the reduction of ALT was of low certainty. OCA trials with high certainty reported evidence about the increase of pruritus to be considerable (RR 3.65, 95% CI 1.62–8.21; I² = 71%) along with the evidence of an increase of 18 mg/dl of low-density lipoprotein cholesterol (LDLc) (MD). We used downgrading for issues of heterogeneity, small sample size, or imprecision. In aggregate, the quality of evidence which supports OCA for histological benefit and SGLT2 inhibitors for reduction of hepatic steatosis is of moderate to high quality, while biochemical markers like ALT and some open-label studies we found to have lower quality evidence. We present a detailed RoBs assessment and GRADE results in Figure 3 and Table 1, respectively.
 | Figure 3. RoB assessment by RoB2. [Click here to view] |
Table 1. GRADE evidence profile of SGLT2i versus OCA for MAFLD and fibrosis.
| Certainty assessment | Summary of findings | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Outcome | Studies (n, design) | RoB | Inconsistency | Indirectness | Imprecision | Other bias | Overall certainty of evidence | Relative effect (95% CI) | Anticipated absolute effect |
| Histological fibrosis improvement (≥1 stage) | 3 RCTs (FLINT, REGENERATE, [34]) | Not serious | Moderatea | Not serious | Some concernsb | N/A | ⊕⊕⊕o MODERATE | RR 2.29 (1.35–3.88) | 125 more per 1,000c (from 34 more to 279 more |
| NASH resolution | 2 RCTs (FLINT, REGENERATE) | Not serious | Not serious | Not serious | Seriousd | N/A | ⊕⊕oo LOW | RR 1.71 (0.98–2.98) | 34 more per 1,000e (from 1 fewer to 97 more) |
| LFC (MRI-PDFF/CAP) | 2 RCTs [30,31] | Not serious | Not serious | Not serious | Some concernsf | N/A | ⊕⊕⊕o MODERATE | SMD −0.41 (−0.73 to −0.09) | Small-to-moderate reduction versus control |
| ALT change | 2 RCTs [30,31] | Some concernsg | Not serious | Not serious | Serioush | N/A | ⊕⊕oo LOW | MD −5.92 U/L (−12.95 to 1.11) | Uncertain reduction in ALT |
| Weight/BMI change | 2 RCTs [30,31] | Some concerns | Not serious | Not serious | Some concernsi | N/A | ⊕⊕⊕o MODERATE | MD −2.15 kg (−3.85 to −0.45) | Approx. 2 kg weight loss |
| Adverse events — pruritus (OCA) | 3 RCTs (REGENERATE, FLINT, [34]) | Not serious | Moderatej | Not serious | Not serious | N/A | ⊕⊕⊕⊕ HIGH | RR 3.65 (1.62–8.21) | Large increase in pruritus risk |
| Adverse events — LDL rise (OCA) | 2 RCTs (REGENERATE, FLINT) | Not serious | Not serious | Not serious | Not serious | N/A | ⊕⊕⊕⊕ HIGH | MD +18 mg/dl | Consistent LDL increase |
CI = confidence interval; RR = risk ratio; MD = mean difference; SMD = standardized mean difference.
aModerate heterogeneity (I² = 64%) due to variation in dose and population.
bWide CI; small sample size in one trial.
cBaseline risk estimated from placebo/lifestyle control arms; extrapolated per 1,000 patients over 12–18 months.
dCI crosses line of no effect (RR 0.98–2.98).
eControl event rate for NASH resolution ≈ 50/1,000 from pooled placebo groups.
fLiver fat studies small (n = 123); downgraded for imprecision.
gSome concerns due to one open-label ALT study.
hALT CI crosses zero; total sample size low.
iWeight/BMI data from two small RCTs; wide CI.
jSubstantial heterogeneity for pruritus (I² = 71%).
3. RESULT AND DISCUSSION
3.1. NAFLD pathophysiology and progression
Table 2 shows the comparative efficacy of SGLT2i versus OCA in NASH/Fibrosis patients. NAFLD develops through a multifactorial process that unfolds in two distinct stages.
Table 2. Clinical characteristics of studies evaluating SGLT2i and OCA in NAFLD and fibrosis.
| S.NO | Author | Location | Study design | Sample size | Gender | Intervention group | Control group | Population | Outcome | Trial registry number |
|---|---|---|---|---|---|---|---|---|---|---|
| 1. | Lin et al. [22] | China | Multicentre, double blind, randomised, placebo controlled trial | 78:76 (154) | ≥ 18 years, both men and women | Dapagliflozin 10 mg OD, 48 w | Placebo | MASH (T2DM/NON T2DM) | Reduction of steatosis, ballooning, lobular inflammation, and fibrosis. MASH resolution without worsening of fibrosis and fibrosis improvement without worsening of MASH. ADE’S: COVID-19, insomnia, and gout, UTI, DKA | NCT03723252 |
| 2. | Shojaei et al. [23] | Iran | RCT | 70:70 (140) | 20 to 70 years both men and women | Empagliflozin, 6 m | Control | NAFLD (T2DM) | Improves LFC, liver enzyme levels, and systolic blood pressure | IRCT20210811052150N1 |
| 3 | Taha et al. [30] | Egypt | Interventional, randomized, prospective controlled-group open-label trial | 33:22 (55) | >18 years, both men and women | Empagliflozin (10 mg) + lifestyle advice, 6 m | Lifestyle advice, 6 m | NAFLD Without DM | ↓ CAP, ALT, improves hepatic steatosis with no significant changes in fibrosis. Weight reduction | NCT05694923 |
| 4. | Khaliq et al.[24] | Pakistan | RCT | 60:60:60 (180) | 20 to 70 years both men and women | Ertugliflozin 15 mg, Pioglitazone 30 mg, 24 w | Placebo | NAFLD (T2DM) | Improves liver enzyme and reduces LFC significantly improves steatosis | ACTRN12624000032550 |
| 5. | Shi et al. [25] | China | Prospective, open-label, randomized, controlled clinical trial | 42:42 (84) | 18–75 years both men and women | Dapagliflozin 10 mg, 24 w | Control | NAFLD (T2DM) | significant reduction in LFC and PFC, improves serum ALT, TNF-α, and IL-6 levels as well as an improvement in liver fibrosis | ChiCTR2100054612 |
| 6. | Takahashi et al. [26] | Japan | Multicenter, open- label RCT | 27:28 (55) | 20–80 years both men and women | Ipragliflozin 50 mg, 6 m | Control | NAFLD (T2DM) | Glycemic control, obesity, and hepatic outcomes, including liver fibrosis, reduced the severity of ballooning, resulting in NASH resolving. ADE: Gastric cancer | UMIN000015727 jRCTs071180069 |
| 7. | Kinoshita et al. [27] | Japan | Randomized, open-label, three-arm, active control study | 32:33:33 (98) | ≥ 20 years, both men and women | Dapagliflozin 5 mg, 28 w | Pioglitazone (7.5–15 mg/day) or Glimepiride (0.5 1 mg/day) ,28 w | NAFLD (T2DM) | Reduction of VFA, decrease of serum insulin level, increase of adiponectin level and the increase of the L/S ratio thus improve steatosis. | UMIN 000021291 |
| 8. | Taheri et al. [31] | Iran | Randomised, double-blind, placebo-controlled trial | 43:47 (90) | 20–65 years, both men and women | Empagliflozin (10 mg), + METs 24 w | Placebo + METs 24 w | NAFLD without T2DM | ↓ALT, CAP, LSM causes a reduction liver fat grade and steatosis, improved without significant changes in FIB-4 (fibrosis), Weight reduction. AED’s: Fungal vaginal infections, allergic reactions. | IRCT20190122042450N1 |
| 9. | Tobita et al. [47] | Japan | Single-centered, double-blind, randomized, prospective study | 12:10 (22) | ≥20 years, both men and women | Dapagliflozin (5 mg), 12 w | Teneligliptin (20 mg),12 w | NAFLD without T2DM | ↓ ALT along with ferritin, weight loss, No fibrosis, and steatosis improvement. | UMIN000027304 |
| 10. | Shimizu et al. [28] | Japan | Randomized, active-controlled, open-label trial, | 35:28 (63) | ≥ 20 years, both men and women | Dapagliflozin (5 mg/day) group 24 weeks. | Control group | NAFLD (T2DM) | Weight reduction, reduction VAT improves liver steatosis and fibrosis | UMIN000022155 |
| 11. | Kuchay et al. [29] | India | Prospective, open-label, randomized clinical study | 25:25 (50) | >20 years both men and women | Empagliflozin 10 mmg/day, 20 w | Control | NAFLD (T2DM) | Reduces liver fat and improves ALT levels ADEs: balanoposthitis | NCT02686476 |
| 12. | Alkhouri et al. [17] | USA | Double-blind, randomised, placebo-controlled phase 1 study | Study 747–117 20:20 (40) Study 747–118 8:8 versus 4:4 (24) | >18 years, both men and women | OCA 10 or OCA 25, 85 d OCA 10 mg, OCA 25 mg, 4 w | Placebo, 85 d OCA 25 mg, OCA 10 mg, 4 w | NASH with fibrosis Child-Pugh Class A (CP-A) NASH cirrhosis versus Control | Pruritus was the most frequent ADE’s, ↑ OCA levels with fibrosis severity. | NCT03439254 |
| 13. | Younossi et al. [32] | USA | Randomised phase 3 study (REGENERATE Trail) | 407:404:407 (1,218) | 18 to 85 years, both men and women | OCA 10 mg,0CA 25 mg ,18 m | Placebo, 18 m | NASH | Fibrosis improvement with no NASH worsening & NASH resolution | NCT02548351 |
| 14. | Sanyal et al. [16] | USA | Randomised phase 3 study (REGENERATE Trail) | 825:827:825 (2,477) | 18 to 85 years, both men and women | OCA 10 mg, 0CA 25 mg,18 m | Placebo, 18 m | NASH | Pruritus, dyslipidemia, and gallstone-related events occurred at a higher incidence with OCA 25 mg compared with placebo. Antifibrotic and anti-inflammatory effects show improvement in liver stiffness without fibrosis | NCT02548351 |
| 15. | Alam et al. [34] | Bangladesh | RCT | 18:18 (36) | 18 to 65 years, both men and women | OCA 20 mg+ lifestyle, 24 w | Lifestyle, 24 w | NAS ≥ 5 | Improved NASH and fibrosis irrespective of glycemic conditions and weight loss. fatigue and itching were observed. | NCT03836937 |
| 16. | Tetri et al. [33] | USA | Multicentre, randomised, placebo-controlled trial (FLINT Trail) | 141:142 (283) | >18 years, both men and women | OCA 25 mg, 72 w | Placebo, 72 w | NASH | Improved liver histology, NAS and developed pruritus &↑ LDLc | NCT01265498 |
↑- Increase, ↓- Decrease, ADEs- Adverse drug events, ALT- Alanine aminotransferase, CAP- Controlled Attenuation Parameter, DKA-Diabetic ketoacidosis, LFC- Liver Fat Content, LSM – Liver Stiffness Measurement, METs- Metabolic Equivalent Task, NAFLD- Nonalcoholic Fatty Liver Disease, NAS-NAFLD Activity Score, NASH- Nonalcoholic steatohepatitis, OCA- Obeticholic Acid, PFC-Proton Fat Content RCT- Randomised Controlled Trials, SGLT-2i- Sodium-glucose cotransporter-2 inhibitors, TAG-Triacylglycerol, UTI-Urinary Tract infection, VAT- Visceral Adipose Tissue, VFA- Visceral Fat Area.
The initial phase of this process involves the building up of fat in the hepatic tissue, which subsequently results in insulin resistance. The subsequent phase encompasses cellular and molecular alterations linked to oxidative stress, alongside in the liver the oxidation of fatty acids in the liver, triggered by various factors such as cytokine-mediated injury, elevated insulin levels, hepatic iron accumulation, and oxidative lipid damage contribute to alterations in the extracellular matrix, energy imbalance, and shifts in immune function [35].
3.2. Mechanism of SGLT2Is versus OCA in NAFLD
SGLT2i improves NAFLD and NASH by decreasing hepatic fat content, promoting weight loss, and improving insulin sensitivity, which can lead to decreased hepatic steatosis [36]. In addition, these inhibitors may reduce inflammation and fibrosis by decreasing lipid genesis, suppressing inflammatory cytokines, and activating Peroxisome Proliferator-Activated Receptor alpha, which enhances fatty acid oxidation. They also increase glucagon secretion, which induces gluconeogenesis and β-oxidation, further maximising their liver-supportive effects. Moreover, SGLT2i may exert anti-inflammatory effects by modulating the autonomic nervous system activity, specifically by suppressing sympathetic outflow and enhancing vagal tone, which can reduce Kupffer cell activation [36]. On the other hand, OCA is a pioneering selective FXR nuclear agonist known for its anticholestatic and liver-protective effects, which are predominantly localised within the hepatic tissue, gastrointestinal tract, adrenal cortex, and renal system, and plays a crucial role in the biosynthesis and enterohepatic recycling of bile acids [37]. OCA, known chemically as 6α-ethyl-chenodeoxycholic acid, acts as a semi-synthetic analogue of CDCA and reveals a notable 100-fold augmentation in its affinity for the FXR when contrasted with CDCA [38]. It is essential for managing the metabolism of lipids, glucose, and bile acids in the liver. Upon binding to FXR, OCA activates various metabolic and anti-inflammatory pathways, leading to improved liver histology in conditions like NASH by reducing inflammation and fibrosis [39]. In addition, OCA influences bile acid synthesis and transport, contributing to its therapeutic effects [40]. The possible mechanism of SGLT2i and OCA in NAFLD improvement was shown in Figure 4 [41], Figure 5 [42], respectively.
 | Figure 4. Mechanism of SGLT2i in NAFLD improvement [47]. [Click here to view] |
 | Figure 5. Mechanism of OCA in NAFLD improvement [48] . [Click here to view] |
3.3. Efficacy of SGLT2 inhibitors
In NAFLD, SGLT2i, especially Dapagliflozin, Empagliflozin, Ertugliflozin, and Ipragliflozin have proven to be effective in promoting weight loss, decreasing hepatic fat content, and enhancing liver enzymes. Nevertheless, they have little effect on advanced fibrosis. Evidence for advanced fibrosis regression with SGLT2i remains limited, as only Dapagliflozin is effective for fibrosis; benefits are stronger for steatosis, enzymes, and weight.
3.3.1. Reduction of liver enzymes
The World Gastroenterology Organisation indicates a resource-sensitive approach whereby liver injury biomarkers such as AST, ALT, and gamma-glutamyl transferase (GGT) may assist in assessing NAFLD [50]. AST, ALT, and GGT levels were considerably lowered by Dapagliflozin (5–10 mg) and Empagliflozin (10 mg). There is a significant reduction in ALT level in both diabetic and nondiabetic individuals [23–25,29–31], but an observational study by Dos Santos and Baer Filho [43] states that these enzyme levels were reduced even when there was no weight loss, which indicates less liver inflammation and cellular stress.
3.3.2. Hepatic fat
Several studies have observed the positive impact of SGLT2i on hepatic fat accumulation in patients with NAFLD or NASH.
Empagliflozin [23,29] and Ertugliflozin [24] reduce hepatic fat content with reductions corresponding to weight loss. Dapagliflozin 10 mg significantly reduced LFC and proton fat content (PFC) [25], and a study by Kinoshita et al. [27], Shimizu et al. [28] identified that Dapagliflozin 5 mg reduces visceral fat area (VFA), increases adiponectin levels, enhances adipose tissue function, visceral adipose tissue (VAT), but Marjot et al. [45] showed there are no changes in Triacylglycerol level and fat fraction with Dapagliflozin 10 mg in insulin-resistant-obese patients. A significant reduction in liver fat grade causes lower liver stiffness measurement (LSM) with the Empagliflozin group in nondiabetic patients [31]. This shows that SGLT2i is effective for hepatic fat reduction, which improves hepatic steatosis.
Findings from multiple clinical studies showed that both Dapagliflozin 5 and 10 mg effectively improve hepatic ballooning, lobular inflammation, and fibrosis, showing NASH resolution without worsening of fibrosis and fibrosis improvement without worsening of NASH [22,25,28]. Complementary evidence shows that Ipragliflozin 50 mg reduced the severity of ballooning, resulting in NASH resolution [26].
Tofogliflozin decreased Keratin-18 levels, a marker associated with liver cell death and histological improvement [44]. Dapagliflozin lowered TNF-α and IL-6 concentrations, improving hepatic injury and inflammatory status [25].
3.3.3. NASH resolution without worsening of fibrosis
NASH is an advanced stage of NAFLD defined by liver steatosis, inflammation, hepatocellular injury, and varying degrees of fibrosis [40]. Resolution of steatohepatitis is defined as the no detectable evidence of fatty liver disease or only simple steatosis without steatohepatitis, as indicated by NAFLD Activity Scores (NAS) of 0–1 for inflammation, 0 for ballooning, and any score for steatosis [46].
An RCT conducted by Tobita et al. [47] reported Dapagliflozin-treated non diabetic group showed a reduction in Serum ferritin, a biomarker for identifying NAFLD patients at increased risk of developing NASH and severe fibrosis. It also reported that no significant changes were observed in Type IV collagen 7s, Fibrosis 4 index, and other fibrosis biomarkers implies a limited effect on liver fibrosis.
Empagliflozin showed a reduction in controlled attenuation parameter (CAP) but without significant improvement in liver fibrosis [23,29–31]. Thus, SGLT2i, especially Empagliflozin, is effective for hepatic fat reduction with little effect on fibrosis helps in the prevention of NASH by improving hepatic steatosis, and Dapagliflozin is effective for NASH resolution.
3.3.4. Combination therapy benefits
The combination of Dapagliflozin and Pemafibrate, administered in a case report by Imamura and Kinugawa [48], resulted in increased triglyceride reduction and improved metabolic function than either of the drugs alone. This signifies the achievement of synergistic benefits for patients the complex metabolic disorders.
3.3.5. Weight loss and metabolic changes
Both Dapagliflozin and Empagliflozin caused weight loss by reducing body fat and increasing insulin sensitivity. A study by Neeland et al. [49] reported a unique metabolic action of empagliflozin—it alters glycerol metabolism, facilitates lipid breakdown, and does not boost hepatic glucose production in non-NAFLD/non diabetic obese individuals.
3.4. Efficacy of OCA
The FDA stopped using OCA for NAFLD/MASH in 2023 and recently approved Resmetirom and Semaglutide. Nonetheless, studies are still being conducted to assess OCA's effectiveness in NAFLD. The comparative pharmacodynamic analysis of OCA, semaglutide, and Resmetirom in translational mouse models of MASH, published in 2025, showed that OCA significantly slowed the progression of MASH by reducing α-SMA expression, indicating possible antifibrotic activity [51]. However, more time is needed to verify its effect on liver fibrosis.
3.4.1. Liver enzyme reduction and histological improvement
Evidence from clinical studies shows that OCA at 10–20 mg leads to significant improvements in AST, ALT, and GGT [52]. Moreover, the OCA dose needs to be increased in advanced liver disease, which implies that there is a requirement for dose adjustments in patients [17].
In the Younossi et al. [32] study, there is significant histological improvements, such as liver stiffness, were resolution in both with and without diabetic patients with Fibrosis and NASH after 18 months of OCA treatment [16,32].
3.4.2. NASH resolution and fibrosis
Although the Younossi et al. [32] study confirmed no significant NASH resolution and fibrosis, Neuschwander-Tetri et al. [33] and Brunt et al. [53] reported a key histological improvement, such as Hepatocellular Ballooning, Steatosis, Lobular Inflammation, Fibrosis with OCA (25 mg), but the proportion of improvement does not differ significantly between treatment and placebo group and prevents NAFLD progression. Moreover, a dose-dependent effect of OCA and reported, with 25 mg of OCA being more effective than 10 mg in reducing inflammation and ballooning, though steatosis remained the same [54].
An RCT conducted by Alam et al. [34] showed significant improvement of fibrosis with NASH resolution in the OCA 20 mg with lifestyle changes group, irrespective of diabetic status. Thus, this implies the importance of lifestyle modifications in NAFLD patients.
3.4.3. Lipid management and combination therapy
The CONTROL trial by Pockros et al. [55] found in their study that co-administration of OCA with atorvastatin helps manage OCA-induced dyslipidemia by reducing LDLc and low-density lipoprotein-P to below baseline levels. This suggests the need for combination therapy to counteract the lipid abnormalities compromising efficacy.
3.4.4. Weight loss
Findings from the Neuschwander-Tetri et al. [33] and Alam et al. [34] studies show that OCA 25 mg and OCA 20 mg with lifestyle modifications significantly reduce body weight.
3.5. Safety and adverse events
3.5.1. SGLT2 inhibitors
Usually, well-tolerated with mild adverse events such as urinary tract infections and genital infections. The major adverse effects, such as urogenital infections, diabetic ketoacidosis (DKA), COVID-19, insomnia, gastric cancer, gout, balanoposthitis, skin reactions, appetite change, arthralgia, balanitis, hypoglycaemia, and so on [22,26,29,56]. In addition, rare but serious complications include euglycemic DKA, especially in perioperative fasting, acute illness, or compliance low-carbohydrate or ketogenic diet [57]. Combination therapies (e.g., Dapagliflozin + Pemafibrate) enhance metabolic benefits without significant adverse outcomes [48].
3.5.2. Obeticholic acid
Dose-dependent pruritus, dyslipidemia, increased low-density lipoprotein (LDL), fatigue, abdominal discomfort, arthralgia, and gallstones are significant concerns [26]. In addition, serious ADR includes liver injury, hepatic decompensation [58]. Co-administration of atorvastatin reduces lipid abnormalities, improving the long-term safety profile [55]. Patients with advanced fibrosis require dose monitoring due to increased plasma OCA levels.
4. LIMITATIONS
The included studies show significant heterogeneity in methodologies and outcomes, which limits the compatibility and result synthesis. Only SGLT2i had nondiabetic-specific data available, and OCA results included mixed populations, which limited subgroup analyses.
In addition, the exclusion of non-English publications may exhibit language bias, and publication bias occurs due to the limited access to unpublished studies. Variations in the study quality, with a few lacking randomisation or blinding, affect the reliability of the findings. In addition, the scarce availability of studies, particularly those conducted in nondiabetic populations, restricts the generalisability. Moreover, limited access to the journals leads to selection bias and reduces the comprehensiveness of the findings
5. CONCLUSION
Recently FDA approved Resmetirom and Semaglutide for NAFLD. Our study observed that both SGLT2i and OCA showed potential options for the management of NAFLD, with each having its distinctive mechanism of action, efficacy, and safety profiles. SGLT2i such as Dapagliflozin, Empagliflozin, Ertugliflozin, and Ipragliflozin reveal notable hepatoprotective effects by reducing serum ferritin, lowering Keratin 18 levels, and decreasing.
CAP and LSM, with a contributing reduction in hepatic decompensation events, respectively. All SGLT2i showed significant reduction in liver enzymes, weight, and improved glycaemic control, which mitigates insulin resistance and prevents the progression of T2DM. However,
Empagliflozin effectively reduces hepatic fat content, whereas Dapagliflozin shows NASH resolution without worsening fibrosis. Empagliflozin has been linked with a higher risk of adverse drug events (ADEs), particularly vaginal yeast infections and urinary tract infections.
On the contrary, OCA has exhibited marked histological changes, such as reductions in hepatocellular ballooning, steatosis, lobular inflammation, and fibrosis, and improved liver enzyme profiles. However, there is an increased LDL, decreased HDL, and a slight rise in triglyceride levels is observed. While a slight weight loss was observed with an increased incidence of ADEs, such as pruritus and dyslipidemia. SGLT2i may be more suitable for patients with obesity and insulin resistance, while OCA might be highly effective in advanced liver disease and fibrosis. Furthermore, therapy selection should be based on individual patient characteristics and specific goals of therapy. An extended investigation is necessary to confirm definitive conclusions regarding the comparative efficacy and safety of these two drug classes in the management of NAFLD.
6. LIST OF ABBREVIATIONS
ADE, Adverse Drug Event; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; AUC, Area Under the Curve; BA, Bile Acid; CAP, Controlled Attenuation Parameter; CDCA, Chenodeoxycholic Acid; DKA, Diabetic Ketoacidosis; DPP4i, Dipeptidyl Peptidase-4 Inhibitors; FDA, Food and Drug Administration; FIB, Index – Fibrosis Index; FXR, Farnesoid X Receptor; GGT, Gamma-Glutamyl Transferase; GLP1RAs, Glucagon-Like Peptide-1 Receptor Agonists; HDL, High-Density Lipoprotein; K18, Keratin 18; LDL, Low-Density Lipoprotein; LDLc, Low-Density Lipoprotein Cholesterol; LDLpc, Low-Density Lipoprotein Particle Concentration; LSM, Liver Stiffness Measurement; MAFLD, Metabolic Dysfunction-Associated Fatty Liver Disease; MASH, Metabolic dysfunction-Associated Steatohepatitis; MUFA, Monounsaturated Fatty Acid; NAFLD, Nonalcoholic Fatty Liver Disease; NAS, NAFLD Activity Score; NEFA, Nonesterified Fatty Acids; OCA, Obeticholic Acid; PPAR Alpha, Peroxisome Proliferator-Activated Receptor Alpha; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PUFA, Polyunsaturated Fatty Acid; RCT, Randomized Controlled Trial; SFA, Saturated Fatty Acid; SGLT2 Inhibitors, Sodium-Glucose Cotransporter-2 Inhibitors; SF, Serum Ferritin; T2DM, Type 2 diabetes mellitus; TZD, Thiazolidinedione; UTI, Urinary tract infection.
7. ACKNOWLEDGMENTS
We extend our heartfelt gratitude to Dr Thenmozhi G for her exceptional guidance and consistent support throughout the research process.
8. AUTHOR CONTRIBUTIONS
All authors contributed significantly to the study’s conceptualisation and design, as well as acquisition of data, or analysis and interpretation of data; took part in drafting the article or critically revising the manuscript for important intellectual content; approved to submit to the current journal and agree to be responsible for all aspects of the work. All the authors meet the eligibility criteria for authorship as per the International Committee of Medical Journal Editors (ICMJE) guidelines.
9. FINANCIAL SUPPORT
There is no funding to report.
10. CONFLICTS OF INTEREST
The authors report no financial or any other conflicts of interest in this work.
11. ETHICAL APPROVALS
This study does not involve experiments on animals or human subjects.
12. DATA AVAILABILITY
All data generated and analysed are attached to this research article.
13. PUBLISHER’S NOTE
All claims expressed in this article are solely those of the authors and do not necessarily represent those of the publisher, the editors and the reviewers. This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.
14. USE OF ARTIFICIAL INTELLIGENCE(AI)- ASSISTED TECHNOLOGY
The authors affirm that no AI-assisted tools were used during the writing and editing of the manuscript, and confirm that none of the images were AI-manipulated or generated.
REFERENCES
1. Grander C, Grabherr F, Tilg H. Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options. Cardiovasc Res. 2023;119(9):1787–98. CrossRef
2. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73(1):202–9. CrossRef
3. Wang H, Sun R, Yang S, Ma X, Yu C. Association between serum ferritin level and the various stages of non-alcoholic fatty liver disease: a systematic review. Front Med. 2022;9:934989. CrossRef
4. Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nature Med. 2018;24(7):908–22. CrossRef
5. Samy AM, Kandeil MA, Sabry D, Abdel-Ghany AA, Mahmoud MO. From NAFLD to NASH: understanding the spectrum of non-alcoholic liver diseases and their consequences. Heliyon. 2024;10(9):e30387. CrossRef
6. Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nature Rev Gastroenterol Hepatol. 2013;10(11):656–65. CrossRef
7. Younossi ZM, Henry L. Understanding the burden of nonalcoholic fatty liver disease: time for action. Diabetes Spectr. 2024;37(1):9–19. CrossRef
8. Jeele MOO, Mohamed HN, Addow ROB, Hassan M, Adam B. Insights Into Non-Alcoholic Fatty Liver Disease and Diabetes Mellitus in Somalia: prevalence and Risk Factors. Diabetes Metabolic Syndrome Obesity Targets Therapy. 2025;18:507–14. CrossRef
9. Gadiparthi C, Spatz M, Greenberg S, Iqbal U, Kanna S, Satapathy SK, et al. NAFLD epidemiology, emerging pharmacotherapy, liver transplantation implications and the trends in the United States. J Clin Translational Hepatol. 2020;8(2):215. CrossRef
10. Nassir F. NAFLD: mechanisms, treatments, and biomarkers. Biomolecules. 2022;12(6):824. CrossRef
11. Chen VL, Morgan TR, Rotman Y, Patton HM, Cusi K, Kanwal F, et al. Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD practice guidance. Hepatology. 2025;81(1):312–20. CrossRef
12. Zou CY, Sun Y, Liang J. Comparative efficacy of diabetes medications on liver enzymes and fat fraction in patients with nonalcoholic fatty liver disease: a network meta-analysis. Clinics Res Hepatol Gastroenterol. 2023;47(1):102053. CrossRef
13. Dardi I, Kouvatsos T, Jabbour SA. SGLT2 inhibitors. Biochem Pharmacol. 2016;101:27–39. CrossRef
14. Mirarchi L, Amodeo S, Citarrella R, Licata A, Soresi M, Giannitrapani L. SGLT2 inhibitors as the most promising influencers on the outcome of non-alcoholic fatty liver disease. Int J Mol Sci. 2022;23(7):3668. CrossRef
15. Chapman RW, Lynch KD. Obeticholic acid—a new therapy in PBC and NASH. Br Med Bull. 2020;133(1):95–104. CrossRef
16. Sanyal AJ, Ratziu V, Loomba R, Anstee QM, Kowdley KV, Rinella ME, et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre cirrhotic fibrosis due to non-alcoholic steatohepatitis. J Hepatol. 2023;79(5):1110–20. CrossRef
17. Alkhouri N, Lacerte C, Edwards J, Poordad F, Lawitz E, Lee L, et al. Safety, pharmacokinetics and pharmacodynamics of obeticholic acid in subjects with fibrosis or cirrhosis from NASH. Liver Int. 2024;44(4):966–78. CrossRef
18. U.S. Food and Drug Administration. FDA approves treatment for serious liver disease known as 'MASH' [Internet]. Silver Spring, MD: U.S. Food and Drug Administration; 2025 [cited 2026 Jan 29]. Available from: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash
19. Page MJ, Mckenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372(Suppl 1):71. CrossRef
20. Mcguinness LA, Higgins JPT. Risk-of-bias visualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021;12(1):55–61. CrossRef
21. Schünemann HJ, Neumann I, Hultcrantz M, Brignardello-Petersen R, Zeng L, Murad MH, et al. GRADE guidance 35: update on rating imprecision for assessing contextualized certainty of evidence and making decisions. J Clin Epidemiol. 2022;150:225–42. CrossRef
22. Lin J, Huang Y, Xu B, Gu X, Huang J, Sun J, et al. Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial. BMJ (Clin Res Ed). 2025;389:83735. CrossRef
23. Shojaei F, Erfanifar A, Kalbasi S, Nikpour S, Gachkar L. The effect of empagliflozin on non-alcoholic fatty liver disease-related parameters in patients with type 2 diabetes mellitus: a randomized controlled trial. BMC Endocrine Disord. 2025;25(1):52. CrossRef
24. Khaliq A, Badshah H, Shah Y, Rehman IU, Khan KU, Ming LC, et al. The effect of ertugliflozin in patients with nonalcoholic fatty liver disease associated with type 2 diabetes mellitus: a randomized controlled trial. Medicine. 2024;103(45):e40356. CrossRef
25. Shi M, Zhang H, Wang W, Zhang X, Liu J, Wang Q, et al. Effect of dapagliflozin on liver and pancreatic fat in patients with type 2 diabetes and non-alcoholic fatty liver disease. J Diabetes Complications. 2023;37(10):1086. CrossRef
26. Takahashi H, Kessoku T, Kawanaka M, Nonaka M, Hyogo H, Fujii H, et al. Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD. Hepatol Commun. 2022;6(1):120–32. CrossRef
27. Kinoshita T, Shimoda M, Nakashima K, Fushimi Y, Hirata Y, Tanabe A, et al. Comparison of the effects of three kinds of glucose-lowering drugs on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, open-label, three-arm, active control study. J Diabetes Invest. 2020;11(6):1612–22. CrossRef
28. Shimizu M, Suzuki K, Kato K, Jojima T, Iijima T, Murohisa T, et al. Evaluation of the effects of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obesity Metab. 2019;21(2):285–92. CrossRef
29. Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care. 2018;41(8):1801–8. CrossRef
30. Taha BO, Kobeisy MA, Abdelmohsen E, Abdelrhman T, Abokresha MM, Hassanein ZM, et al. Outcomes of empagliflozin in nondiabetic fatty liver patients: a randomized controlled trial. J Taibah Univ Med Sci. 2025;20(4):525–32. CrossRef
31. Taheri H, Malek M, Ismail-Beigi F, Zamani F, Sohrabi M, Reza Babaei M, et al. Effect of empagliflozin on liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease without diabetes: a randomized, double-blind, placebo-controlled trial. Adv Therapy. 2020;37(11):4697–708. CrossRef
32. Younossi ZM, Stepanova M, Nader F, Loomba R, Anstee QM, Ratziu V, et al. Obeticholic acid impact on quality of life in patients with nonalcoholic steatohepatitis: REGENERATE 18-month interim analysis. Clin Gastroenterol Hepatol. 2022;20(9):2050–8. CrossRef
33. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385(9972):956–65. CrossRef
34. Alam S, Tarannum N, Habib S. Decreased dose and shorter duration of obeticholic acid in nonalcoholic steatohepatitis patient: a randomized control trial. Int J Clin Exp Med. 2022;15(9):282–92. CrossRef
35. Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, et al. Non alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocrine Disord. 2022;22(1):63. CrossRef
36. Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Imajo K, et al. Hepatoprotective effect of SGLT2 inhibitor on nonalcoholic fatty liver disease. Diabetes Res Open Access. 2020;2020(S1):17. CrossRef
37. Abenavoli L, Falalyeyeva T, Boccuto L, Tsyryuk O, Kobyliak N. Obeticholic acid: a new era in the treatment of nonalcoholic fatty liver disease. Pharmaceuticals. 2018;11(4):104. CrossRef
38. Makri E, Cholongitas E, Tziomalos K. Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease. World J Gastroenterol. 2016;22(41):9039. CrossRef
39. Al Mahtab M, Akbar SMF, Roy PP, Rahim MA, Yesmin SS, Islam SB. Treatment of nonalcoholic steatohepatitis by obeticholic acid: current status. Euroasian J Hepato-Gastroenterology. 2022;12(Suppl 1):S46. CrossRef
40. Schuster S, Cabrera D, Arrese M, Feldstein AE. Triggering and resolution of inflammation in NASH. Nature Rev Gastroenterol & Hepatol. 2018;15(6):349–64. CrossRef
41. Li H, Hou Y, Xin W, Ding L, Yang Y, Zhang Y, et al. The efficacy of sodium-glucose transporter 2 inhibitors in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Pharmacol Res. 2025;213:107647. CrossRef
42. Keshvani C, Kopel J, Goyal H. Obeticholic acid—a pharmacological and clinical review. Future Pharmacol. 2023;3(1):238–51. CrossRef
43. Ribeiro Dos Santos L, Baer Filho R. Treatment of nonalcoholic fatty liver disease with dapagliflozin in non-diabetic patients. Metab Open. 2020;5:100028. CrossRef
44. Luo Q, Wei R, Cai Y, Zhao Q, Liu Y, Liu WJ. Efficacy of off label therapy for non-alcoholic fatty liver disease in improving non-invasive and invasive biomarkers: a systematic review and network meta-analysis of randomized controlled trials. Front Med. 2022;9:793203. CrossRef
45. Marjot T, Green CJ, Charlton CA, Cornfield T, Hazlehurst J, Moolla A, et al. Sodium-glucose cotransporter 2 inhibition does not reduce hepatic steatosis in overweight, insulin-resistant patients without type 2 diabetes. JGH Open. 2020;4(3):433–40. CrossRef
46. Tong XF, Wang QY, Zhao XY, Sun YM, Wu XN, Yang LL, et al. Histological assessment based on liver biopsy: the value and challenges in NASH drug development. Acta Pharmacol Sin. 2022;43(5):1200–9. CrossRef
47. Tobita H, Yazaki T, Kataoka M, Kotani S, Oka A, Mishiro T, et al. Comparison of dapagliflozin and teneligliptin in nonalcoholic fatty liver disease patients without type 2 diabetes mellitus: a prospective randomized study. J Clin Biochem Nutr. 2021;68(2):173–80. CrossRef
48. Imamura T, Kinugawa K. Combination therapy using pemafibrate and dapagliflozin for metabolic dysfunction-associated fatty liver disease. Inter Med. 2023;62(9):1371–83. CrossRef
49. Neeland IJ, De Albuquerque Rocha N, Hughes C, Ayers CR, Malloy CR, Jin ES. Effects of empagliflozin treatment on glycerol-derived hepatic gluconeogenesis in adults with obesity: a randomized clinical trial. Obesity. 2020;28(7):1254–62. CrossRef
50. Sanyal D, Mukherjee P, Raychaudhuri M, Ghosh S, Mukherjee S, Chowdhury S. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes. Indian J Endocrinol Metab. 2015;19(5):597–601. CrossRef
51. Zhang R, Li X, Liang X, Kuang Y, Chen X, Niu Y, et al. Comparative pharmacodynamic analysis of resmetirom, semaglutide and obeticholic acid in translational mouse models of MASH. Explor Endocr Metab Dis. 2025;2:101433. CrossRef
52. Zhao J, Li B, Zhang K, Zhu Z. The effect and safety of obeticholic acid for patients with nonalcoholic steatohepatitis: a systematic review and meta-analysis of randomized controlled trials. Medicine. 2024;103(7):e37271. CrossRef
53. Brunt EM, Kleiner DE, Wilson LA, Sanyal AJ, Neuschwander-Tetri BA, NASH CRN. Improvements in histologic features and diagnosis associated with improvement in fibrosis in NASH: results from the NASH clinical research network treatment trials. Hepatol (Baltimore Md). 2019;70(2):522. CrossRef
54. Kulkarni AV, Tevethia HV, Arab JP, Candia R, Premkumar M, Kumar P, et al. Efficacy and safety of obeticholic acid in liver disease—a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2021;45(3):101675. CrossRef
55. Pockros PJ, Fuchs M, Freilich B, Schiff E, Kohli A, Lawitz EJ, et al. CONTROL: a randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients. Liver Int. 2019;39(11):2082–93. CrossRef
56. Mo M, Huang Z, Liang Y, Liao Y, Xia N. The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: an updated meta-analysis. Digestive Liver Dis. 2022;54(4):461–8. CrossRef
57. Thiruvenkatarajan V, Meyer EJ, Nanjappa N, Van Wijk RM, Jesudason D. Perioperative diabetic ketoacidosis associated with sodium-glucose co-transporter-2 inhibitors: a systematic review. Br J Anaesthesia. 2019;123(1):27–36. CrossRef
58. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375(7):631–43. CrossRef