Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis

Bandyopadhyay, Sanjay; Das, Saibal; Samajdar, Shambo Samrat; Joshi, Shashank R.

doi:10.1016/j.dsx.2023.102849

Cited by 22 publications

(7 citation statements)

References 51 publications

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“…В исследовании STEP 5 средняя потеря веса при приеме семаглутида в дозе 2,4 мг к 104-й неделе составила 15,2% от исходного уровня по сравнению с 2,6% при приеме плацебо [45] Определение структурно связанных пептидных примесей и их характеристика является важнейшей задачей в фармацевтической разработке. Данные примеси могут возникать в результате разложения во время производства или хранения, а также влиять на эффективность и безопасность готового продукта [48]. В качестве примесей семаглутида могут выступать пептиды несовершенной структуры, образующиеся в результате вставки не желаемой аминокислоты или делеции (отсутствие одной или нескольких аминокислотных остатков), окисления или рацемизации аминокислот [49].…”

Section: Discussionunclassified

Comparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutide

Ametov,

Shokhin,

Rogozhina

et al. 2024

Farm. farmakol. (Pâtigorsk)

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Semaglutide is a representative of analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently used in Russia for the treatment of type 2 diabetes mellitus (T2DM; in monotherapy and in combination therapy), including patients with obesity and overweight.The aim of the work was to conduct a comparative assessment of the physicochemical properties, a biological activity, bioequivalence and safety, including tolerability and immunogenicity, of the drug Quincent® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Promomed Rus LLC, Russia) and the drug Ozempic® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) when administered to healthy volunteers.Materials and methods. To assess the degree of similarity of the study drug Quincenta® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Promomed Rus LLC, Russia) with a chemically synthesized active substance to the original (reference) drug Ozempic® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Novo Nordisk A/S, Denmark), a comparative study of physicochemical properties and a biological activity was carried out. To assess the bioequivalence of the study drug and the reference drug, an open randomized parallel comparative study with the participation of healthy volunteers (n=54), 54 participants of which had been included in the population, was conducted. The volunteers were randomized into 2 groups in a 1:1 ratio, and received a single dose subcutaneously either of the study drug (domestic semaglutide at a dose of 0.5 mg) or the reference drug (foreign semaglutide at a dose of 0.5 mg). The mode of administration was in the morning on an empty stomach. A semaglutide concentration was determined in serum samples using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to semaglutide in the human serum by ELISA was carried out with a microplate photometer using ready-made kits pre-validated by the manufacturer. The conclusion about the bioequivalence of the compared drugs was made using an approach based on the assessment of 90% confidence intervals for the ratios of the geometric mean values of the parameters Cmax, AUC(0–t) of semaglutide in the measurement original units.Results. The results of the comparative analysis of the study drug and the reference drug demonstrate the comparability of their physicochemical properties and biological activity. The results of the clinical study demonstrated the bioequivalence of the test drug and the reference drug. Thus, the pharmacokinetic parameters of the drugs were comparable to each other: the Cmax value for the study drug was 42.088±8.827 ng/ml, for the reference drug Ozempic® it was 42.2556±7.84. Herewith, the half-life for the study drug and the reference drug was 168.39±39.47 and 157.99±28.57 hours, respectively. The resulting 90% confidence intervals for the ratio of the Cmax and AUC0–t values of the study drug and the reference drug were 90.89–109.15 and 91.66–111.27%, respectively. The tolerability of the drugs in the volunteers was notified as good. No adverse events were recorded during the study. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to Russian-made semaglutide were detected in the blood serum of the volunteers, which indicated the lack of Results. The results of a comparative analysis of the study drug and the reference drug demonstrate the comparability of physicochemical properties and biological activity. The results of the clinical study demonstrated the bioequivalence of the study drug and the reference drug. Thus, the pharmacokinetic parameters of the drugs were comparable to each other: the Cmax value for the study drug was 42.088±8.827 ng/ml, for the reference drug Ozempic® this figure was 42.2556±7.84. At the same time, the half-life for the study drug and the reference drug was 168.39±39.47 and 157.99±28.57 hours, respectively. The resulting 90% confidence intervals for the ratio of the Cmax and AUC0–t values of the study drug and the reference drug were 90.89–109.15 and 91.66–111.27%, respectively. Tolerability of the drugs in volunteers was noted as good. No adverse events were recorded during the study. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to Russian-made semaglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.Conclusion. In the course of the study, the comparability of the physicochemical properties and biological activity of the studied Russian drug with the chemically synthesized active substance Quincenta® to the reference drug Ozempic® was confirmed: the activity range of the studied drugs was within 80–120% in relation to the standard sample of semaglutide. The bioequivalence and a similar safety profile, including the immunogenicity and tolerability of the Russian drug Quincenta® (semaglutide 1.34 mg/ml, Promomed Rus LLC, Russia) were shown in comparison with the foreign drug Ozempic® (semaglutide 1.34 mg/ml, Novo Nordisk A/C, Denmark).

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Section: Discussionunclassified

Comparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutide

Ametov,

Shokhin,

Rogozhina

et al. 2024

Farm. farmakol. (Pâtigorsk)

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“…Furthermore, an improved 6-min walking distance and a 21% reduction in NT-proBNP levels confirmed that excessive weight plays a crucial role in HFpEF and the reduction of hemodynamic load also by a significant BP decrease (−4.9 mmHg) may be of great benefit in these patients. Moreover, semaglutide showed the ability to improve NASH, with no worsening of fibrosis in NASH patients, leading to reduced serum transaminase, liver fat content and liver stiffness ( 113 , 114 ).…”

Section: Pharmacological Treatment Of Obesitymentioning

confidence: 99%

Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities

Sarzani,

Landolfo,

Di Pentima

et al. 2024

Front. Med.

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Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight and obesity almost tripled worldwide. The accumulation of “visceral” adipose tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure to overt arterial hypertension, from insulin-resistance to overt type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and obstructive sleep apnea. The increasing use of innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i), is changing the management of obesity and its related cardiovascular complications significantly. These drugs, first considered only for T2DM treatment, are now used in overweight patients with visceral adiposity or obese patients, as obesity is no longer just a risk factor but a critical condition at the basis of common metabolic, cardiovascular, and renal diseases. An adipocentric vision and approach should become the cornerstone of visceral overweight and obesity integrated management and treatment, reducing and avoiding the onset of obesity-related multiple risk factors and their clinical complications. According to recent progress in basic and clinical research on adiposity, this narrative review aims to contribute to a novel clinical approach focusing on pathophysiological and therapeutic insights.

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“…However, liver enzymes and liver steatosis, as well as cardiometabolic risk factors (weight, triglycerides, very low-density lipoprotein cholesterol, and HbA 1c among subjects with T2DM) were improved, without new safety concerns beyond the already known (nausea, vomiting, diarrhoea) [ 12 ]. Finally, in a recent meta-analysis [ 13 ], semaglutide use in people with NAFLD or NASH showed a significantly improvement in liver enzymes and metabolic parameters after 24 weeks of treatment. Moreover, liver stiffness was reduced.…”

Section: Semaglutide In Non-alcoholic Fatty Livermentioning

confidence: 99%

“…Moreover, liver stiffness was reduced. However, adverse events, namely gastrointestinal and gallbladder diseases, were more frequent than with placebo [ 13 ]. Similarly, an ongoing study is investigating the effect of semaglutide in subjects with non-cirrhotic NASH compared with placebo [ 14 ].…”

Section: Semaglutide In Non-alcoholic Fatty Livermentioning

confidence: 99%

Potential New Therapeutic Implications of Semaglutide: New Colours of the Rainbow?

Gouveri,

Popovic,

Papanas

2023

Diabetes Ther

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Semaglutide is a potent glucagon-like peptide 1 receptor agonist for the management of type 2 diabetes mellitus. In addition to this, it has emerging potential clinical implications. First, there is accumulating preliminary data on its potential role in type 1 diabetes mellitus. In this setting, we need to know which patient subgroups may benefit more. Furthermore, its role in non-alcoholic fatty liver and in non-alcoholic steatohepatitis is emerging. Other potential therapeutic implications of semaglutide include kidney disease, Alzheimer disease and pulmonary diseases. Nonetheless, we still need much more information on its long-term efficacy, safety and utility in these new implications before any definitive conclusions may be drawn for everyday practice.

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Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis

Cited by 22 publications

References 51 publications

Comparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutide

Comparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutide

Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities

Potential New Therapeutic Implications of Semaglutide: New Colours of the Rainbow?

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