Farmaci antidiabetici e rene

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Pubblicato il 10 novembre 2016

Antidiabetic Drugs and the Kidney

Farmaci antidiabetici e rene

Antidiabetic Drugs and the Kidney

Riccardo Candido

S.S. Centro Diabetologico Distretto 3 Azienda Sanitaria Universitaria Integrata di Trieste

Corrispondenza a: Riccardo Candido; S.S. Centro Diabetologico Distretto 3 Azienda Sanitaria Universitaria Integrata di Trieste Via Puccini 50 34148 Trieste; E-mail: riccardocandido@yahoo.it

Abstract

Il diabete rappresenta una malattia in continua espansione. L’aumento dell’incidenza e della prevalenza di questa patologia in tutto il mondo si associa ad un aumento della frequenza delle complicanze, specie nei paesi industrializzati, ove il diabete rappresenta la causa più frequente di malattia renale cronica. Ampi studi prospettici randomizzati hanno dimostrato che la gestione intensiva del diabete, con l’obiettivo di raggiungere valori glicemici quanto più possibile vicini alla normoglicemia, è in grado di ritardare l’insorgenza di microalbuminuria e la progressione del danno renale nei pazienti con diabete tipo 1 e tipo 2. Tuttavia molto meno chiaro è il ruolo dello stretto compenso glicemico nei pazienti diabetici con insufficienza renale avanzata e in dialisi. In aggiunta nel paziente nefropatico diabetico la terapia con ipoglicemizzanti orali deve essere attentamente e periodicamente monitorata poiché il declino della funzione renale al di sotto dei 60 ml/min di filtrato glomerulare può determinarne molteplici alterazioni farmacocinetiche ed esporre il paziente a gravi effetti collaterali (ipoglicemia in primis) qualora non se ne consideri una prudente riduzione di dose o addirittura la sospensione. Le attuali evidenze sembrano suggerire, la metformina come farmaco di prima scelta per i casi con insufficienza renale moderata ed in alternativa o in associazione i DPP4-inibitori, che possono essere utilizzati anche nei pazienti con insufficienza renale terminale o in dialisi, e che hanno il vantaggio di essere neutri sul peso e di non indure ipoglicemie oltre ad avere studi effettuati ad hoc in questa popolazione. Particolare attenzione va posta con l’utilizzo dei secretagoghi glucosio indipendenti, repaglinide compresa, per il rischio ipoglicemico e per la mancanza di studi con questi farmaci. Infine anche la terapia insulinica gioca un ruolo importante nella terapia dell’iperglicemia in corso di insufficienza renale, ma è assolutamente necessario uno stretto monitoraggio glicemico al fine di ridurre le ipoglicemie.

Tabella 1. Terapia non insulinica nel diabete di tipo 2 con insufficienza renale cronica

Stadio IRC	Lieve	Moderata	Grave	Dialisi
eGFR	>60 ml/min	30-60 ml/min	15-30 ml/min	<15 ml/min
Metformina	≥2 g/die	Non indicato (utilizzabile)	NO	NO
Acarbosio	Da titolare	Da titolare	NO	NO
Gliptine
Sitagliptin	100 mg/die	50 mg/die	25 mg/die	25 mg/die
Vildagliptin	100 mg/die	50 mg/die	50 mg/die	50 mg/die
Saxagliptin	5 mg/die	2.5 mg/die	2.5 mg/die	NO
Linagliptin	5 mg/die	5 mg/die	5 mg/die	5 mg/die
Alogliptin	25 mg/die	12.5 mg/diea	6.25 mg/die	6.25 mg/die
GLP1 agonisti
Exenatide	Dosi usuali	Cautelab	NO	NO
Exenatide LAR	Dosi usuali	NOc	NO	NO
Liraglutide	Dosi usuali	Dosi usuali	NO	NO
Lixisenatide	Dosi usuali	Cautelab	NO	NO
Dulaglutide	Dosi usuali	Dosi usuali	NO	NO
Sulfoniluree	Da titolare (preferendo gliclazide o glipizide)	Da titolared (preferendo gliclazide o glipizide)	NO	NO
Repaglinide	Da titolare	Non indicato (utilizzato)	NO	NO
Pioglitazone	Dosi usuali	Dosi usuali	Dosi usuali	NOe
Gliflozine
Dapagliglozin	Dosi usuali	NO	NO	NO
Empagliflozin	Dosi usuali	NO	NO	NO
Canagliflozin	Dosi usuali	NO	NO	NO

(adattato da Standard Italiani per la cura del diabete mellito AMD-SID, 2016)

Note:

^aLa riduzione della dose da 25 a 12.5 mg/die è prevista quando eGFR scende sotto 50 ml/min.

^bCautela necessaria quando eGFR è inferiore a 50 ml/min
^cFarmaco non indicato quando eGFR è inferiore a 50 ml/min

^dAlcune sulfoniluree (gliquidione, glimepiride) hanno metabolismo prevalentemente epatico, ma non sono state comunque studiate in modo esteso in pazienti con insufficienza renale; una accurata titolazione della dose è comunque raccomandabile, almeno per eGFR inferiore a 60 ml/min

^eIlpioglitazone è controindicato per eGFR inferiore a 5 ml/min

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pubblicata il 10 novembre 2016
Da

Riccardo Candido

S.S. Centro Diabetologico Distretto 3 Azienda Sanitaria Universitaria Integrata di Trieste

Corrispondenza a: Riccardo Candido; S.S. Centro Diabetologico Distretto 3 Azienda Sanitaria Universitaria Integrata di Trieste Via Puccini 50 34148 Trieste; E-mail: riccardocandido@yahoo.it

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