Cardioprotective effects of antihyperglycemic medications

Šećerna bolest posljednjih desetljeća pokazuje sve veću globalnu prevalenciju. Uz hipertenziju i hiperlipidemiju, šećerna bolest je vodeći čimbenik za kardiovaskularni rizik. Budući da velik dio volesnika s kardiovaskularnim bolestima ima i šećernu bolest, antihiperglikemijski lijekovi ne bi smjeli imati štetan utjecaj na nijedan kardiovaskularni ishod. Kako je kod starije generacije nekih antihiperglikemijskih lijekova uočen negativan kardiovaskularni ishod, došlo je do potrebe uvođenja novih lijekova, uz zahtjev da se za svaki novi lijek, osim djelotvornosti na snižavanje glukoze u plazmi, ispita kardiovaskularna sigurnost. Započeto je puno kliničkih ispitivanja o kardiovaskularnim ishodima, neke od njih su već završene dok su druge još u tijeku. Ta klinička ispitivanja istražuju utjecaj inhibitora dipeptidil peptidaze 4, inhibitora natrij-glukoza kotransportera 2 i agonista receptora glukagonu sličnog peptida-1 te prema do sada objavljenim rezultatima pobuđuju veliki optimizam. Najveća prednost se daje inhibitorima natrij-glukoza kotransportera 2 jer su u istraživanjima pokazali najuvjerljiviju kardiovaskularnu korist. Posebno mjesto zauzimaju bolesnici sa šećernom bolesti i zatajivanjem srca s obzirom na to da gotovo polovica bolesnika sa zatajenjem srca ima i šećernu bolest. Nakon što je došlo do spoznaje da bi inhibitori natrij-glukoza kotransportera 2 mogli protektivno djelovati na ishod zatajenja srca u bolesnika sa šećernom bolesti, postavilo se pitanje mogu li sličan ishod imati i u bolesnika bez šećerne bolesti te biti prvi lijekovi koji bi istovremeno djelovali na zatajenje srca s reduciranom i očuvanom frakcijom izbacivanja. Kliničke studije su upravo u završnoj fazi, a sve dok konačni podaci nisu dostupni, preporuka liječenja pacijenata sa šećernom bolesti i zatajenjem srca sa specifičnim antihiperglikemijskim lijekovima trebala bi se izbjegavati, dok optimalno liječenje treba ovisiti o individualnim karakteristikama bolesnika.The global prevalence of diabetes mellitus in recent decades has been increasing. Along with hypertension and hyperlipidemia, diabetes is a leading factor for cardiovascular risk. Since many patients with cardiovascular diseases have diabetes, antihyperglycemic drugs should not have a damaging effect on any cardiovascular outcome. Negative cardiovascular outcomes were observed with the older generation of some antihyperglycemic drugs, and there was a need for the development of new antidiabetic agents. In addition to the efficacy of lowering plasma glucose, cardiovascular safety measurements were mandatory for each new drug. Some clinical trials that investigate cardiovascular benefit of antidiabetic drugs on cardiovascular system are already completed while the others are still ongoing. Mentioned clinical trials investigate the effect of dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) and glucagon-like peptide-1 receptor agonists, and, according to the results published so far, give great optimism. The highest benefit is given to SGLT-2 inhibitors because they showed the highest cardiovascular benefit in clinical trials. Special attention was given to patients with diabetes mellitus and heart failure, considering that almost half of the patients with heart failure have diabetes mellitus. The results of these experiments showed that SGLT-2 inhibitors act protectively on the outcome of heart failure in patients with diabetes mellitus. A subject of further experiments could be the effect of sodium-glucose co-transporter-2 inhibitors on patients with heart failure without diabetes. In theory, SGLT-2 inhibitors could also be the first medications with beneficial outcomes in heart failure with reduced and in heart failure with preserved ejection fraction. Clinical trials are now in final stages, and until their completion, treating patients with diabetes mellitus and heart failure with specific antihyperglycemic drugs, should be avoided. Optimal treatment should depend on the individual characteristics of the patient