A review of Non-Alcoholic Fatty Liver Disease (NAFLD) clinical trials registered in the clinical trials registry of India

INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma. It is currently the most common cause of chronic liver disease worldwide, affecting nearly one-quarter of the adult population globally.[1] In India, reported prevalence varies widely (approximately 10%–30%), reflecting heterogeneity in study populations and diagnostic approaches.[2] NAFLD is strongly associated with obesity, insulin resistance, dyslipidemia, and type 2 diabetes mellitus and is widely considered the hepatic manifestation of metabolic syndrome.[3] Lifestyle modification remains the cornerstone of management, as no single pharmacological therapy has achieved universal regulatory approval for NAFLD. Nevertheless, several drug classes, including insulin sensitizers, antioxidants, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and emerging antifibrotic agents-are under active clinical evaluation.[4-6] In India, the Clinical Trials Registry-India (CTRI) serves as the national platform for prospective trial registration. Reviewing NAFLD trials registered in CTRI can provide insights into national research trends, therapeutic priorities, and methodological gaps. This brief communication summarizes the profile of NAFLD-related clinical trials registered in CTRI. METHODS A retrospective descriptive review was conducted using the publicly accessible Clinical Trials Registry–India (CTRI) database.[7] The term “NAFLD” was searched under the condition/disease field, and trials registered up to July 1, 2024, were included. Studies related to NASH were also considered when relevant. Eligible studies were human interventional or observational trials conducted in India. Duplicate, withdrawn, unrelated, or preclinical studies were excluded. Extracted variables included study design, trial phase, geographic location, sponsorship, interventions studied, outcome measures, and recruitment status. Data were analyzed descriptively. RESULTS A total of 38 NAFLD-related clinical trials were identified, with registrations increasing steadily after 2017. Interventional studies predominated (34/38; 89.4%), while only four trials were observational. Randomized controlled trials accounted for 68.4% of studies, although details on blinding and trial phase were frequently missing. Most trials were single-center studies conducted in Southern India, reflecting regional concentration of research infrastructure. Academic institutions sponsored over half of the trials, whereas industry sponsorship was limited. The commonly evaluated pharmacological agents included metformin, pioglitazone, Vitamin E, GLP-1 receptor agonists, and SGLT2 inhibitors. Several trials assessed herbal or nutraceutical interventions, including curcumin and Nigella sativa, and a smaller number focused on lifestyle-based interventions. Primary outcome measures largely relied on liver enzymes, ultrasonographic assessment of steatosis, transient elastography, and metabolic parameters. Histological endpoints and long-term follow-up were uncommon. DISCUSSION This analysis highlights a gradual increase in NAFLD clinical trial activity in India; however, the overall volume remains modest compared with global research output. The dominance of interventional studies is encouraging, yet the scarcity of longitudinal observational studies limits the understanding of disease progression in Indian populations.[3] Inconsistent reporting of trial phase, blinding, and primary endpoints within CTRI entries points to gaps in registry data quality. Most trials relied on short-term surrogate endpoints, which restrict the conclusions regarding disease modification and fibrosis regression.[5,8] Traditional agents such as metformin, Vitamin E, and pioglitazone continue to dominate Indian trials, while newer agents with promising international evidence, particularly GLP-1 receptor agonists and SGLT2 inhibitors-remain underrepresented.[8,9] The presence of herbal and traditional medicine trials reflects India’s integrative healthcare landscape, although challenges related to standardization, reproducibility, and translational relevance persist.[10] Overall, future NAFLD research in India would benefit from multicenter collaboration, longer follow-up, standardized outcome measures, improved registry documentation, and balanced evaluation of pharmacological and nonpharmacological therapies. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.