The efficacy of liraglutide-based drugs on the model of induced metabolic syndrome in experimental animals

Abstract

Today, there is an annualincrease in the prevalence of obesityandoverweightworldwide.Thisproblem is becomingparticularlyrelevant,sincetheseconditionsserve as keyriskfactors for the development of anumber of cardiovascularandmetabolicdisorders,including type 2diabetesmellitus(T2DM).On the territory of the Russian Federation, drugswerepresentedasagonists of glucagon-like peptide of the first type (GLP-1)receptors, the activesubstance of which was producedexclusively by biotechnologicalmeans. It is important to notethat solid-phasechemicalsynthesisisalsooneof the alternativemethods for obtainingGLP-1analogues. A significantadvantage of thismethodoverbiotechnologicalsynthesisis the exclusion of spontaneousamino acid substitutionsand the absence of impuritiescharacteristicofthismethod.The aim. Evaluation of the biological activity of the domestic medicinal product liraglutide (Enligria®, solution for subcutaneous administration, 6 mg/ml, PROMOMED RUS LLC), obtained by chemical synthesis, and a foreign reference drug (Saxenda®,solutionforsubcutaneousadministration,6 mg/ml,NovoNordiskA/C),obtainedbiotechnologically.Materials and methods. The effectiveness of liraglutide preparations was evaluated using a model of induced metabolic syndrome in CBA×C57BL/6 SPF mice (n=36,age6months)according to changes in body weight,feedintake,bloodglucoseandlipid levels, and adiposetissuemass.Results. According to the results of the study, it was shown that Enligria® and Saxenda® drugs have comparable efficacy parameters and statistically significantly (p < 0.05) reduce body weight (13.6±2.1% and 13.3±3.3%, respectively), glucose levels (18 ± 3% and 16 ± 9%), triglycerides (32 ± 12% and 40 ± 18 %) and cholesterol (16 ± 7% and 18 ± 9%) in the blood. Enligria® reduced the mass of structural subcutaneous fat by 32 ± 3% (p < 0.0001), and visceral fat by 34 ± 4% (p < 0.0001). The studiedliraglutidepreparationsshowed a pronouncedhypoglycemiceffect,observedinalldoseranges. The observedhypoglycemiceffectwasdose-dependent.Conclusion. The results of the work indicate the high effectiveness of the synthetic drug Enligria®, which is expressed in reducing body weight and improving metabolic parameters.

Keywords

• glp-1 agonist
• liraglutide
• peptide
• metabolic syndrome
• type 2 diabetes mellitus
• obesity
• weight loss
• glucose
• lipids
• experiment