Dolgoročni klinični izidi zdravil za zdravljenje bolnikov s sladkorno boleznijo tipa 2 : doktorska disertacija

Žerovnik, Špela (author), Locatelli, Igor (mentor), Kos, Mitja (comentor)

Glavni cilj zdravljenja sladkorne bolezni tipa 2 (SB2) je preprečevanje kroničnih zapletov sladkorne bolezni, tj. mikrovaskularnih in srčno-žilnih (makrovaskularnih) zapletov. Farmakoterapija SB2 se je v zadnjem desetletju precej spremenila, predvsem na račun razvoja novejših antihiperglikemičnih zdravil iz skupin zaviralcev dipeptidil peptidaze 4 (DPP-4), analogov glukagonu podobnega peptida 1 (GLP-1) in zaviralcev natrijevih glukoznih koprenašalcev 2 (SGLT2). Klinične študije, na podlagi katerih so ta zdravila pridobila dovoljenje za promet, so vrednotile kratkoročne klinične izide zdravljenja (delež glikiranega hemoglobina), ne pa tudi dolgoročnih (npr. pojavnosti srčno-žilnih zapletov, mikrovaskularnih zapletov). Od leta 2008 Agencija za hrano in zdravila v ZDA (ang. Food and Drug Administration – FDA) za vsa novejša antihiperglikemična zdravila po prihodu na trg zahteva predložitev podatkov o srčno-žilni varnosti, saj se je za učinkovino iz skupine tiazolidindionov, rosiglitazon, izkazalo, da poveča tveganje za miokardni infarkt. Za dokazovanje srčno-žilne varnosti je bilo izvedenih veliko kliničnih študij, t. i. študij srčno-žilne varnosti (ang. cardiovascular outcomes trials – CVOT), katerih namen je bil dokazati, da posamezno antihiperglikemično zdravilo ne poveča tveganja za srčno-žilne dogodke v primerjavi s placebom. Čeprav so študije CVOT primarno zasnovane za vrednotenje varnostnega vidika zdravljenja z novejšimi antihiperglikemičnimi zdravili, so nekatere pokazale celo ugoden vpliv določenih učinkovin iz skupin zaviralcev SGLT2 in analogov GLP-1 na zmanjšanje pojavnosti pomembnih neželenih srčno-žilnih dogodkov (ang. major adverse cardiovascular events – MACE). Učinkovine iz skupine zaviralcev SGLT2 so zmanjšale tudi tveganje za hospitalizacijo zaradi srčnega popuščanja. Ker so te študije vključevale bolnike s SB2 in obstoječo srčno-žilno boleznijo oziroma prisotnimi dejavniki tveganja za srčno-žilni dogodek, so rezultati prenosljivi le na manjši delež bolnikov s SB2 v klinični praksi. Vpliv antihiperglikemičnih zdravil na pojavnost tako srčno-žilnih kot tudi mikrovaskularnih zapletov pri bolnikih s SB2 v klinični praksi bi lahko najhitreje in najučinkoviteje ovrednotili z opazovalnimi raziskavami.

• Language: Slovenian
• Keywords: Sladkorna bolezen tip 2, farmakoterapija
• Work type: Dissertation
• Typology: 2.08 - Doctoral Dissertation
• Organization: FFA - Faculty of Pharmacy
• Place of publishing: Ljubljana
• Publisher: [Š. Žerovnik]
• Year: 2022
• Number of pages: 191 str.
• PID: 20.500.12556/RUL-143831
• UDC: 616.379-008.64(043.3)
• COBISS.SI-ID: 96687619
• Publication date in RUL: 13.01.2023

Secondary language

• Language: English
• Title: Long-term clinical outcomes of medicines for patients with type 2 diabetes

Abstract

The main goal of treatment of type 2 diabetes (T2D) is to prevent its long-term chronic complications, especially microvascular and cardiovascular (macrovascular) complications. Pharmacotherapy of T2D has changed significantly over the past decade, mainly due to the market introduction of novel classes of antidiabetic medicines: dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The clinical trials based on which these antidiabetic medicines obtained marketing authorisation evaluated short-term (e.g. levels of glycated haemoglobin, HbA1c) rather than long-term clinical outcomes (e.g. incidence of cardiovascular and microvascular complications). Since 2008, however, the US Food and Drug Administration has mandated that cardiovascular safety data be submitted for all novel antidiabetic medicines entering the market, as one of the medicines in the thiazolidinedione group – rosiglitazone – has been shown to increase the risk of myocardial infarction. To this end, many post-marketing clinical trials, known as cardiovascular outcome trials (CVOTs), have been conducted to date with the aim of demonstrating that, compared to placebo, the individual antidiabetic medicine is not associated with an increased risk of cardiovascular events. Although these trials were primarily designed to evaluate the safety aspects of novel antidiabetic medicines, some have even shown a beneficial effect of medicines from the SGLT2i and GLP-1RA drug classes in reducing the risk of major adverse cardiovascular events (MACE). Medicines from the SGLT2i drug class also reduced the risk of hospitalisation due to heart failure. However, these studies included patients with established cardiovascular disease and patients with cardiovascular risk factors who had not yet developed cardiovascular disease. Therefore, the results of the studies can only be generalised to a small proportion of patients with T2D in routine clinical practice. The effect of antidiabetic medicines on the risk of both cardiovascular and microvascular complications in patients with T2D in routine clinical practice could be assessed most rapidly and effectively with observational studies.