Incretin-based therapies for the treatment of type 2 diabetes

Šećerna bolest (ŠB) jedan je od glavnih javnozdravstvenih problema koji prerasta u pandemiju. Prevalencija šećerne bolesti tipa 2 (ŠBT2) u značajnom je porastu u mlađoj populaciji, na što utječe porast pretilosti. Osam je temeljnih patofizioloških poremećaja, koji se obično nazivaju "Omniozni oktet", uključeno u patogenezu ŠBT2. Osnovna terapija ŠBT2 podrazumijeva promjenu životnog stila uz metformin kao antidijabetik prve linije terapije. Terapija druge linije podrazumijeva dodatak drugog oralnog antidijabetika, agonista receptora glukagonu sličnog peptida 1 (GLP-1R) ili inzulina. Sveobuhvatnija definicija uspješnosti liječenja u bolesnika sa ŠBT2 uključuje usporavanje ili zaustavljanje progresije bolesti te redukciju svih čimbenika rizika koji su povezani s mikrovaskularnim i makrovaskularnim komplikacijama (hipertenzija, pretilost, hiperlipidemija, upala). U liječenju ŠBT2 preferiraju se antidijabetici koji osim svog učinka na smanjenje razine glikiranog hemoglobina (HbA1c), imaju izravne pozitivne učinke na druge faktore kardiovaskularnog rizika i nizak rizik od hipoglikemija. Inkretini su nova inovativna terapijska opcija koja uključuje agoniste GLP-1R i inhibitore dipeptidil peptidaze-4 (DPP-4). Ovi antidijabetici imaju brojne pozitivne učinke na više mehanizama uključenih u patofiziologiju ŠBT2, uključujući smanjenje tjelesne mase, krvnog tlaka, povoljni učinak na lipidni profil, potencijalni regenerativni učinak na β stanice i nizak rizik od hipoglikemije. Od velike je važnosti dokazani kardioprotektivni učinak nekih agonista GLP-1R.Diabetes is a major public health problem and is emerging as a pandemic. The prevalence of type 2 diabetes (DMT2) is significantly increasing in younger population, which is affected by obesity worldwide. There are eight core defects implicated in the pathogenesis of DMT2 commonly called the “Ominous Octet”. Pharmacologic therapy of DMT2 has changed dramatically in the last 10 years, with new drugs and drug classes becoming available. The cornerstone of diabetes therapy considers lifestyle changes with metformine added in the first line medication therapy. The second line therapy considers addition of second oral agent, GLP-1R agonist or insulin. A more comprehensive definition of treatment success in patients with DMT2 should include slowing or stopping disease progression and the reduction of all risk factors associated with microvascular and macrovascular diabetic complications (hypertension, obesity, hyperlipidemia, inflammation). We prefer antidiabetic drugs with direct positive impact on other cardiovascular risk factors not only on reducing glycated hemoglobin (HbA1c) and the ones with low risk of hypoglycemia. Incretins are a new innovative therapeutic option that includes GLP-1R agonists and DPP-4 inhibitors. These antidiabetic agents have a number of positive effects on multiple mechanisms involved in pathophysiology of the T2DM, including weight loss, reduction of blood pressure, beneficial effect on the lipid profile, potential regenerative effect on beta cells, and low risk of hypoglycaemia. Of great significance is the proven cardioprotective effect of some GLP-1R agonists