Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial

Alkhouri, Naim; Herring, Robert; Kabler, Heidi; Kayali, Zeid; Hassanein, Tarek; Kohli, Anita; Huss, Ryan; Zhu, Yu; Billin, Andrew N.; Damgaard, Lars Holm; Buchholtz, Kristine; Kjær, Mette; Balendran, Clare A.; Myers, Robert P.; Loomba, Rohit; Noureddin, Mazen

doi:10.1016/j.jhep.2022.04.003

Cited by 129 publications

(75 citation statements)

References 30 publications

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“…Importantly, obeticholic acid, a steroidal FXR agonist, has shown promising results in phase 2 and 3 clinical trials in patients with NASH [283], including the ongoing phase 3 REGENERATE trial, showing improvement of fibrosis on interim analysis without worsening of NASH [284]. Pharmacologic FXR agonism thus remains an important pillar for future combination therapy of NAFLD [285], potentially restoring bile acid metabolism and dampening inflammation.…”

Section: Potential Implications Of Immune Mechanisms In Nafld For The...mentioning

confidence: 99%

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

Peiseler

Schwabe

Hampe

et al. 2022

Journal of Hepatology

248

148

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Section: Potential Implications Of Immune Mechanisms In Nafld For The...mentioning

confidence: 99%

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

Peiseler

Schwabe

Hampe

et al. 2022

Journal of Hepatology

248

148

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“…A phase 2 of 108 patients with NASH evaluated safety of semaglutide 2.4 weekly only, vs in combination with cilofexor (30 or 100 mg daily) and/or firsocostat 20 mg daily. Patients had NASH based on biopsy with F2-F3 fibrosis or MRI-PDFF ≥ 10% and transient elastography (TE) liver stiffness ≥ 7 kPa[ 64 ]. Although 73%-90% of patients experienced adverse effects (mainly gastrointestinal), only 41%-48% had ≥ grade 2 adverse events and only 8 (7.4%) discontinued their study drug.…”

Section: Combination Therapiesmentioning

confidence: 99%

Therapies for non-alcoholic fatty liver disease: A 2022 update

Shen¹,

Singh²,

Esfeh³

et al. 2022

World J Hepatol

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The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and lifestyle interventions to treat this disease by addressing the underlying metabolic syndrome are often limited. Many pharmacological interventions are being studied to slow or even reverse NAFLD progression. This review for hepatologists aims to provide an updated understanding of the pathogenesis of NAFLD, current recommended therapies, and the most promising treatment options that are currently under development.

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“…Liver steatosis measured by MRI-PDFF, CK-18 levels as well as liver stiffness showed greater reduction with combinational treatments compared with semaglutide alone (triple treatment vs. semaglutide monotreatment: –47 vs. –68% relative change for liver fat, –312 vs. –179 U/L for CK-18 and –3.5 vs. –2.5 kPA for transient elastography), whereas changes in body weight were similar between groups (–7.0 to –9.6%). 113…”

Section: Treating People With Nash and Type 2 Diabetesmentioning

confidence: 99%

Novel Antidiabetic Strategies and Diabetologists' Views in Nonalcoholic Steatohepatitis

2021

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Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide with high prevalence, especially in individuals with obesity and type 2 diabetes. Among individuals with type 2 diabetes, the severe insulin resistant subgroup has the greatest risk of NAFLD, likely due to dysfunctional adipose tissue mass but also genetic factors, and may progress earlier to inflammatory and profibrotic nonalcoholic steatohepatitis (NASH). NASH has been associated with increased liver-related as well as cardiovascular morbidity and mortality. International diabetes associations recommend certain screening and treatment strategies for NASH in type 2 diabetes, which, however, bear several limitations such as lack of accurate noninvasive diagnostic tools and targeted treatments. Currently, antihyperglycemic drug concepts based on glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors offer metabolic as well as cardiorenal benefits and provide treatment options for both hyperglycemia and NASH in type 2 diabetes.

show abstract

Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial

Cited by 129 publications

References 30 publications

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

Therapies for non-alcoholic fatty liver disease: A 2022 update

Novel Antidiabetic Strategies and Diabetologists' Views in Nonalcoholic Steatohepatitis

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