Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial

Loomba, Rohit; Abdelmalek, Manal F.; Armstrong, Matthew; Jara, Maximilian; Kjær, Mette; Krarup, Niels; Lawitz, Eric; Ratziu, Vlad; Sanyal, Arun J.; Schattenberg, Jörn M.; Newsome, Philip

doi:10.1016/s2468-1253(23)00068-7

Cited by 116 publications

(69 citation statements)

References 33 publications

(71 reference statements)

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“…Importantly, we also observed a significant improvement in the FIB‐4 score within the entire population and among patients with a history of BS, although not among those without such a history. GLP‐1‐RA therapies have emerged as a promising avenue of research for the treatment of nonalcoholic steatohepatitis (NASH) and associated diseases [23], and previous results have shown improvement in NASH, but not in liver fibrosis [24, 25]. Our results suggest that clinicians can anticipate similar metabolic improvements in patients with a history of BS compared with those without such a history.…”

Section: Discussionsupporting

confidence: 52%

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery

Bonnet,

Tournayre,

Anitcheou

et al. 2023

Obesity

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ObjectiveThis retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m2) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI.MethodsThe authors analyzed data from 129 patients with a BMI ≥ 40 kg/m2, including 39 with (BS+) and 90 without (BS−) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference.ResultsSemaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS− groups.ConclusionsThis study is the first, to the authors’ knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m2 and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.

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Section: Discussionsupporting

confidence: 52%

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery

Bonnet,

Tournayre,

Anitcheou

et al. 2023

Obesity

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“…Given the complexity of liver disease in T2DM with multiple in parts overlapping factors, including lifestyle habits, industrial fructose consumption, smoking, and viral hepatitis (HBV, HCV) that promote disease progression, a multi‐stakeholder approach involving primary care, endocrinologists, and nutritionists besides hepatologists is necessary to provide optimal care 12 . Especially with the advent of emerging pharmacologic treatments of T2DM and obesity, which have shown an improvement in liver injury, require the expertise of endocrinologists and hepatologists alike 29 . Lifestyle interventions, that form the cornerstone of treatment and prevention of disease progression, need close surveillance of nutritionists along with primary care to achieve long‐lasting effects 30 .…”

Section: Discussionmentioning

confidence: 99%

Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes

Michel,

Doll,

Albert

et al. 2024

UEG Journal

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BackgroundType 2 diabetes mellitus (T2DM) is a major risk factor for advanced liver disease. The aim of this prospective cohort study was to assess the prevalence and associated risk factors of liver fibrosis and cirrhosis in primary care centers participating in the diabetes disease management program (DMP) in Germany.MethodsA total of 175 participants with the diagnosis of T2DM were enrolled in two primary care centers. Steatotic liver disease (SLD; hepatic steatosis, ≥275 dB/m), fibrosis (≥8 kPa), and cirrhosis (≥15 kPa) were assessed non‐invasively using vibration‐controlled transient elastography. Multivariable logistic regression analysis was performed to identify clinical predictors of fibrosis and cirrhosis. The AUDIT questionnaire was used to screen for alcohol consumption, and a score ≥8 was considered harmful alcohol consumption.ResultsThe majority of participants were male (62%), and the median age was 66 years (interquartile range 59; 71). The median body mass index was 31.1 kg/m2, with 58.9% of the participants being obese. Harmful alcohol consumption was prevalent in 8.0% and 20.0% of the entire cohort and in those with cirrhosis, respectively. The prevalence of SLD, fibrosis, and cirrhosis was 77.1%, 42.3%, and 12.0%, respectively. In multivariable logistic regression analysis, obesity, and harmful alcohol consumption were associated with the highest odds of fibrosis (odds ratio [OR] 5.198, 95% confidence interval [CI] 2.269–11.908) and cirrhosis (OR 5.615, 95% CI 1.274–24.756), respectively.ConclusionThe prevalence of fibrosis and cirrhosis in patients seen in the diabetes DMP in Germany is high. Obesity and harmful alcohol consumption increase the risk of fibrosis and cirrhosis in people with T2DM. Screening for advanced liver disease and associated risk factors within the DMP program may reduce the liver disease burden in this high‐risk population.

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“…54,55 Exenatide (3 RCTs), liraglutide (6 RCTs), dulaglutide (1 RCT) and semaglutide (4 RCT) have been tested in patients with NAFLD to assess their efficacy. [56][57][58][59][60] All these drugs improve the clinical features of NAFLD, and all reduce plasma levels of aminotransferases.…”

Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

“…Exenatide, liraglutide and dulaglutide reduce hepatic fat content assessed by magnetic resonance; liraglutide and semaglutide reduce the histological features of NASH, thus preventing the worsening of inflammation but have no effect on liver fibrosis stages or in NASHrelated cirrhosis. 58,[61][62][63][64][65] A trial has been designed to evaluate oral semaglutide in hepatic steatosis (NCT03884075) and a pilot study has shown that this new drug formulation improves indexes of hepatic steatosis and fibrosis in T2D subjects. 66 It has been shown that GLP-1 RA enhances insulin sensitivity in the liver and WAT and reduces DNL and WAT lipolysis, possibly with a direct effect on the lipolysis pathway, consequently reducing FFA flux to other tissues, [67][68][69] as shown in Table 1.…”

Section: Glucagon-like Peptide-1 Receptor Agonistsmentioning

confidence: 99%

Why do some glucose‐lowering agents improve non‐alcoholic fatty liver disease whereas others do not? A narrative review in search of a unifying hypothesis

Ciccarelli

Giuseppe

Cinti

et al. 2023

Diabetes Metabolism Res

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Non‐alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are metabolic disorders connected by common pathophysiological mechanisms. Since insulin resistance (IR) and metabolic alterations are common to both conditions, almost all glucose‐lowering agents which improve IR have also been studied in patients with NAFLD. Some have shown great efficacy, others none. Thus, the mechanisms behind the efficacy of these drugs in improving hepatic steatosis, steatohepatitis, and eventually fibrosis remain controversial. Glycaemic control improves T2D, but probably has limited effects on NAFLD, as all glucose‐lowering agents ameliorate glucose control but only a few improve NAFLD features. In contrast, drugs that either improve adipose tissue function, reduce lipid ingestion, or increase lipid oxidation are particularly effective in NAFLD. We therefore hypothesise that improved free fatty acid metabolism may be the unifying mechanism behind the efficacy of some glucose‐lowering agents on NAFLD and may represent the key to NAFLD treatment.

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Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial

Cited by 116 publications

References 33 publications

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery

Obesity and harmful alcohol consumption are predictors for advanced liver disease in the disease management program for type 2 diabetes

Why do some glucose‐lowering agents improve non‐alcoholic fatty liver disease whereas others do not? A narrative review in search of a unifying hypothesis

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