Efficacy of Sodium Glucose Cotransporter 2 Inhibitors on Non-Alcoholic Fatty Liver Disease

Обзор

evaluate the effectiveness of sodium-glucose cotransporter-2 (SGLT.2) inhibitors in improving hepatic steatosis and hepatic fibrosis using imaging biomarkers and histopathology in patients with non-alcoholic fatty liver disease

Подробное описание

2.1 Background (Research Question, Available Data from the literature, Current strategy for dealing with the problem, Rationale of the research that paves the way to the aim(s) of the work). (200-250 words max.) Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver-related health issues worldwide, with prevalence rates reaching up to 30%.The number of cases has been steadily rising, increasing from 391.2 million in 1990 to 882.1 million in 2017.

NAFLD is often linked to one or more components of metabolic syndrome, such as hypertension, dyslipidemia, obesity, and Type 2 diabetes mellitus, along with insulin resistance. Although the exact pathogenesis of NAFLD is not fully understood, there is increasing evidence that insulin resistance and lipid metabolism dysregulation play significant roles in the development of hepatic steatosis. Factors such as a high-fat diet, insulin resistance, obesity, and dysregulated peripheral lipolysis contribute to the increased influx of free fatty acids into the liver, leading to a 'lipotoxic' state within hepatocytes.The accumulation of triacylglycerol in the cytoplasm of hepatocytes manifests histologically as steatosis. Persistent micro-hepatic injury eventually results in endoplasmic reticulum stress and mitochondrial dysfunction, which then contribute to lobular inflammation, cellular apoptosis, and hepatic fibrosis over time.

If left untreated, this manageable condition can lead to serious complications, including advanced cirrhosis, hepatocellular carcinoma, and potentially cardiovascular morbidity.and mortality.Given the serious prognostic implications of NAFLD, effective treatment is essential to prevent disease progression. While weight loss and lifestyle modifications are the primary treatments, pharmacologic options remain limited. Recently, the potential of a novel oral hypoglycemic agent known as sodium-glucose cotransporter 2 (SGLT-2) inhibitors in the treatment of NAFLD has been explored through various animal studies on rodent models and human clinical trials, showing promising effects.

Первичные конечные точки

• determine the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic fibrosis and steatosis in patients with NAFLD using fibroscan and biomarkers [Срок оценки: Baseline]

Критерии участия

Критерии включения

• age >18 years
• both sex

Критерии исключения

• alcohol drinker
• any cause of liver affection (hepatitis, autoimmune…etc)
• patients with kidney function affection

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

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• Tahara A, Takasu T. SGLT2 inhibitor ipragliflozin alone and combined with pioglitazone prevents progression of nonalcoholic steatohepatitis in a type 2 diabetes rodent model. Physiol Rep. 2019 Nov;7(22):e14286. doi: 10.14814/phy2.14286. PMID 31782258
• Wei Q, Xu X, Guo L, Li J, Li L. Effect of SGLT2 Inhibitors on Type 2 Diabetes Mellitus With Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2021 Jun 17;12:635556. doi: 10.3389/fendo.2021.635556. eCollection 2021. PMID 34220701

Идентификаторы

NCT: NCT06739486 · SGLT.2 inhibitors

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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