Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial.

BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity. METHODS: Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively. RESULTS: RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide. CONCLUSION: Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.

The global burden of metabolic disease: Data from 2000 to 2019.

Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.

The placebo response rate and nocebo events in obesity pharmacological trials. A systematic review and meta-analysis.

Background: There is a growing number of trials examining the effectiveness of pharmacotherapies for obesity, however, little is known about placebo and nocebo effect in these trials. Hence, we sought to examine the effect of placebo in obesity trials, to better understand the potential factors affecting clinical endpoints in them. Methods: Medline, Embase, and Cochrane CENTRAL were searched for articles examining weight-loss RCTs examining patients with overweight or obesity in placebo-controlled arms from inception till 25 June 2022. This paper was registered online with PROSPERO (CRD42022302482). A single arm meta-analysis of proportions was used to estimate the primary outcomes, ≥5%, ≥10%, and ≥15% total weight loss - and the adverse effects that patients experienced during the trial. A meta-analysis of means was used to estimate the pooled mean differences of the secondary outcomes including, body weight measurements, lipid levels, glycemic indices, and blood pressure over time. Findings: A total of 63 papers involving 20,454 patients and 69 trials were included. The proportion of patients that had ≥5%, ≥10%, and ≥15% weight loss was 20·4% (CI:16·1% to 25·0%), 8·3% (CI:6·1% to 10·9%), and 6·2% (CI:3·8% to 9·7%), respectively. Analysis by duration of trials showed stepwise increase in proportion of patients with ≥5% and ≥10% weight loss with increasing duration of study. Analysis of secondary outcomes found modest improvement in all analyses. The pooled average rate of overall AEs, serious AEs, and discontinuation was 73·7% (CI:68·0% to 79·0%), 3·4% (CI:2·4% to 4·5%), and 5·2% (CI:4·0% to 6·5%), respectively. In psychiatric complications, the pooled rates of anxiety and depression were 2·7% (CI:1·8% to 3·7%) and 2·5 (CI:1·7% to 3·3%). Interpretation: Our meta-analysis of placebo-treated participants in weight-loss RCTs indicate a significant placebo and nocebo effect. These findings are important to quantify their effect and may inform the design of future RCTs. Funding: This research did not receive additional support from organizations beyond the authors' academic institutions.

Comprehensive Review and Updates on Holistic Approach Towards Non-Alcoholic Fatty Liver Disease Management with Cardiovascular Disease.

PURPOSE OF REVIEW: The global prevalence of non-alcoholic fatty liver disease (NAFLD) presents an unmet need in treating these, often asymptomatic, individuals. In this review, we summarised NAFLD management and described recent developments in non-alcoholic steatohepatitis (NASH) therapeutics that can shape the future of NAFLD. RECENT FINDINGS: A multi-disciplinary effort in promoting sustainable lifestyle measures is paramount, with the goal of either limiting energy surplus alone or in combination with targeting downstream pathways of inflammation and fibrosis. Several antidiabetic medications like PPAR-γ agonist and glucagon-like peptide receptor agonists have beneficial effects on the metabolic profile as well as NASH histology. Vitamin E has shown promise in specific groups of patients with the haptoglobin2 allele protein. Newer drugs have demonstrated promising results in NASH resolution and fibrosis improvement such as obeticholic acid, resmetirom, aramchol, efruxifermin, aldafermin and lanifibranor. Apart from discussing the results of late stage clinical trials and the possible challenges in managing these patients with limited approved therapies, we also discussed the specific management of comorbidities (diabetes, hypertension, hyperlipidaemia, cardiovascular diseases) in NAFLD patients. Treatment strategy needs to target improvements in liver-related outcomes and cardiometabolic profile.

Endothelial-immune crosstalk contributes to vasculopathy in nonalcoholic fatty liver disease.

The top cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, mechanisms of NAFLD-associated vasculopathy remain understudied. Here, we show that blood outgrowth endothelial cells (BOECs) from NAFLD subjects exhibit global transcriptional upregulation of chemokines and human leukocyte antigens. In mouse models of diet-induced NAFLD, we confirm heightened endothelial expressions of CXCL12 in the aortas and the liver vasculatures, and increased retention of infiltrated leukocytes within the vessel walls. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification in NAFLD patients. Functionally, treatment with a CXCL12-neutralizing antibody is effective at moderating the enhanced chemotactic effect of NAFLD BOECs in recruiting CD8+ T lymphocytes. Interference with the CXCL12-CXCR4 axis using a CXCR4 antagonist also averts the impact of immune cell transendothelial migration and restores endothelial barrier integrity. Clinically, we detect threefold more circulating damaged endothelial cells in NAFLD patients than in healthy controls. Our work provides insight into the modulation of interactions with effector immune cells to mitigate endothelial injury in NAFLD.

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies. STUDY SELECTION: Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants. METHODS: A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed. RESULTS: 82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I2=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I2=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I2=89%; 0.29, 0.11 to 0.58, I2=97%), and solid cancers (0.55, 0.46 to 0.65, I2=78%; 0.44, 0.36 to 0.53, I2=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I2=0%; 0.06, 0.04 to 0.08, I2=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I2=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I2=88%; 0.62, 0.54 to 0.70, I2=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I2=92%; 0.77, 0.66 to 0.85, I2=93%), and solid cancers (0.90, 0.88 to 0.93, I2=51%; 0.89, 0.86 to 0.91, I2=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I2=0%; 0.97, 0.83 to 1.00, I2=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines. CONCLUSION: Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272088.

Small bowel adenocarcinoma in Crohn's disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes.

BACKGROUND AND AIMS: Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn's disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA. METHODS: Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects. RESULTS: In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31-2.33) per 1000 CD patients. Only 11% (CI: 0.04-0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18-0.41), and 33% (CI: 0.26-0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA. CONCLUSION: Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.

Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines.

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.

Systematic review with meta-analysis: The prevalence, risk factors and outcomes of upper gastrointestinal tract Crohn's disease.

AIMS: Upper gastrointestinal Crohn's disease (UGI-CD) is an important subclassification of Crohn's Disease (CD). We performed a systematic review and meta-analysis to evaluate the prevalence, risk factors, and clinical outcomes associated with UGI-CD. METHODS: We searched Embase and Medline for articles reporting the clinical information of UGI-CD in CD patients, through 27 October 2020. Disease location and phenotype were coded according to the Montreal classification, and results were pooled with random effects by DerSimonian and Laird model. RESULTS: 26 articles were included. The prevalence of UGI-CD was 13%. UGI-CD was most commonly found in the stomach (56%) and was associated with concurrent ileocolonic involvement (54%). Non-stricturing, non-penetrating UGI-CD was the most common behavioral phenotype (61%). L4-jejunal disease was associated with the highest rates of surgery. Region of origin did not significantly influence the location and phenotype of UGI-CD. Young, male patients presenting with erythema nodosum, aphthous ulcers and stricturing-phenotype are more likely to have UGI-CD, which in turn is linked to increased risk of hospitalization and surgery. CONCLUSION: UGI-CD is present in 13% of patients with CD, and patients with L4-jejunal disease are more likely to require surgery. Further studies examining the effect of ethnicity and region on UGI-CD are needed.

A meta-analysis on the incidence of donor-related depression after liver transplant.

Living donor liver transplantation (LDLT) is increasing, yet gaps exist in the understanding of psychological wellbeing of donors after liver transplant. This meta-analysis seeks to evaluate the incidence and risk factors for donor-related depression after liver transplantation. A search was conducted on Medline and Embase database. Articles assessing incidence of depression in LDLT donors were included. Incidence was pooled after Freeman-Turkey double-arcsine transformation. For risk factors, dichotomous variables were analyzed with generalized linear model, while a conventional meta regression with logit transformation was conducted for continuous variables. Of 1069 abstracts, 40 articles underwent full-text review. Seventeen articles were included. The pooled incidence of depression among 1888 LT donors was 7.66% (CI: 4.47-12.80%). Depression rates were significantly higher in Asian compared to Western studies (RR: 1.73, CI: 1.19-2.52, P = 0.0039). Female gender (P < 0.001), Caucasian ethnicity (P = 0.047), employment status (P < 0.001) and lower education levels (P = 0.044) were significantly associated with depression. Donor relationship with recipients was not a significant risk factor. LDLT remains a core aspect of the treatment of end-stage liver disease. However, the high depression rates after LT suggest that there remains room for improvement in the care of donors' mental health post-transplant.

Glucagon-Like Peptide-1 Receptor Agonists for Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: A Meta-Analysis.

Objective: Non-alcoholic fatty liver disease is highly prevalent in patients with type 2 diabetes mellitus. Studies on glucagon-like peptide-1 receptor agonists for the treatment of non-alcoholic fatty liver disease have reported promising results. Despite this, there has been limited evidence of its efficacy in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. This meta-analysis examined existing evidence on the efficacy of glucagon-like peptide-1 receptor agonists on the management of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Methods: Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles discussing the efficacy of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Values of standardized mean differences (SMD) and risk ratio (RR) were determined for continuous outcomes and dichotomous outcomes respectively. Results: 8 studies involving 1,454 patients from 5 randomized controlled trials and 3 cohort studies were included in the analysis. Our analysis found significant improvements in hepatic fat content, liver biochemistry, body composition, glucose parameters, lipid parameters, insulin sensitivity and inflammatory markers following glucagon-like peptide-1 receptor agonist treatment. Glucagon-like peptide-1 receptor agonists significantly decreased hepatic fat content compared to metformin and insulin-based therapies. Glucagon-like peptide-1 receptor agonists also improved fibrosis markers, but this did not reach statistical significance. Conclusion: With a high prevalence of obesity and non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonist treatment shows promise in improving both diabetes and non-alcoholic fatty liver disease phenotype.

A Time-Based Meta-Analysis on the Incidence of New Onset Diabetes after Liver Transplantation.

NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.

Sodium-Glucose Co-Transporter 2 Inhibitors for Non-Alcoholic Fatty Liver Disease in Asian Patients With Type 2 Diabetes: A Meta-Analysis.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a very common disorder among patients with type 2 diabetes and may share causal relationship. Type 2 diabetes is a risk factor for progression and potential poor outcomes in NAFLD patients. This meta-analysis aimed to analyze the current evidence of sodium-glucose co-transporter-2 inhibitors (SGLT2i), a glucose-lowering drug to improve NAFLD in patients with Type 2 Diabetes. Methods: Medline, Embase and Cochrane Central Register of Controlled Trials were searched for articles examining efficacy of SGLT2i on treatments of NAFLD in type 2 diabetes in July 2020, and articles were sieved. Continuous data were extracted in the form of mean and standard deviation and were pooled with standardized mean difference (SMD). Results: 10 articles involving 555 patients from seven randomized controlled trials (RCTs) and three cohort studies, were included in this meta-analysis. Our analysis revealed significant improvements in hepatic fat content (after treatment: -0.789 (-1.404 to -0.175), p = 0.012; compared with control: -0.923 (-1.562 to -0.285), p = 0.005), AST (After Treatment: -0.539 (-0.720 to -0.357), p < 0.001; compared with control: -0.421 (-0.680 to -0.161), p = 0.001), ALT (after treatment: -0.633 (-0.892 to -0.373), p < 0.001; compared with Control: -0.468 (-0.685 to -0.251), p < 0.001), body composition (BMI: after treatment: -0.225 (-0.456 to 0.005), p = 0.055; compared with Control: -1.092 (-2.032 to -0.153), p = 0.023), glycemic control (HbA1c: After Treatment: -0.701 (-1.098 to -0.303), p = 0.001; compared with control: -0.210 (-0.603 to 0.183), p = 0.295), lipid parameters (Triglycerides: after treatment: -0.230 (-0.409 to -0.052), p = 0.011; compared with control: -0.336 (-0.597 to -0.076), p = 0.011), inflammatory markers (serum ferritin: after treatment: -0.409 (-0.694 to -0.124), p = 0.005; compared with control: -0.814 (-1.688 to 0.059), p = 0.068) after SGLT2i treatment, and when compared against controls. There was a trend in the improvement in fibrosis markers after SGLT2i treatment. Conclusions: SGLT2i is an effective treatment to improve NAFLD among patients with type 2 diabetes. Further studies are needed to understand the direct and indirect effects of SGLT2i on NAFLD and if SGLT2i could prevent the progression of NAFLD or NASH. SGLT2i could potentially be considered for patients with type 2 diabetes and NAFLD, if there are no contraindications.