Международный эндокринологический журнал Том 18, №5, 2022

Цукровий діабет (ЦД) — загальновизнаний чинник ризику серцево-судинних захворювань, тому деяким пацієнтам із групи високого ризику необхідний «агресивний» терапевтичний підхід. Холестерин (ХС) ліпопротеїнів низької щільності (ЛПНЩ) є провідним модифікованим чинником ризику розвитку атеросклеротичних серцево-судинних захворювань (АССЗ). Відомо, що статини — золотий стандарт для контролю вмісту ХС ЛПНЩ і зниження ризиків, пов’язаних з АССЗ; однак багато пацієнтів не досягають цільового рівня ХС ЛПНЩ або не можуть вживати препарати цього класу через асоційовані з ними побічні дії. Нещодавні дослідження нестатинових лікарських засобів, що знижують концентрацію холестерину (езетиміб, інгібітори пропротеїнової конвертази субтилізин-кексинового типу 9), продемонстрували переваги в лікуванні АССЗ; і нові препарати (бемпедоєва кислота, інклісиран) дали багатообіцяючі результати в доклінічних і клінічних дослідженнях. Нові дані свідчать про те, що езетиміб як доповнення до статинів забезпечує додатковий кардіопротекторний ефект. Цей огляд має на меті обговорити місце езетимібу в терапії хворих на ЦД з дисліпопротеїнеміями і розглянути його ефективність і безпеку. Комбіноване використання низькоінтенсивної або помірноінтенсивної терапії статинами й езетимібом задіює два комплементарних один щодо одного механізми: зниження внутрішньоклітинної концентрації ХС з посиленням захоплення ХС ЛПНЩ гепатоцитами і зниження абсорбції ХС у кишечнику. Ці механізми діють синергічно й можуть забезпечити такий же сумарний ефект, як і при використанні високоінтенсивної терапії статинами. Безпека комбінованої терапії еквівалентна безпеці монотерапії інгібіторами ГМГ-КoА-редуктази в аналогічних дозах. Ця комбінація, як правило, переноситься краще, ніж високі дози інгібіторів ГМГ-КоА-редуктази, і має переваги у хворих з ризиком розвитку міопатії і статин-індукованого ЦД 2-го типу. Отже, попри деякі застереження, езетиміб залишається препаратом вибору в арсеналі фармакологічних агентів.

Diabetes mellitus is a well-recognized risk factor for cardiovascular diseases, so an “aggressive” therapeutic approach is necessary for some high-risk patients. Low-density lipoprotein (LDL) cholesterol is the leading modifiable risk factor for the development of atherosclerotic cardiovascular diseases (ACVD). It is known that statins are the gold standard to control LDL cholesterol and reduce the risks associated with ACVD; however, many patients do not achieve their LDL cholesterol target or are unable to use this class of drugs due to associated side effects. Recent stu­dies of non-statin cholesterol-lowering drugs (ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors) have demonstrated benefits in the treatment of ACVD, and new drugs (bempedoic acid, inclisiran) have shown promising results in preclinical and clinical studies. New evidence suggests that prescription of ezetimibe as an addition to statins provides an additional cardioprotective effect. This review aims to discuss the role of ezetimibe in the treatment of patients with diabetes mellitus and dyslipoproteinemia and to consider its efficacy and safety. The combined use of low- or moderate-intensity therapy with statins and ezetimibe involves two complementary mechanisms: a decrease in the intracellular concentration of cholesterol with increased uptake of LDL cholesterol by hepatocytes and a decrease in cholesterol absorption in the intestines. These mechanisms act synergistically and can provide the same overall effect as when using high-intensity statin therapy. The safety of combined therapy is equivalent to that of monotherapy with HMG-CoA reductase inhibitors in similar doses. This combination is generally better tolerated than high doses of HMG-CoA reductase inhibitors and has advantages in patients at risk of myo­pathy and statin-induced type 2 diabetes. Thus, despite some ca­veats, ezetimibe remains the drug of choice in the arsenal of pharmacological agents.

цукровий діабет; езетиміб; огляд

diabetes mellitus; ezetimibe; review

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