A secondary analysis of concurrent use of metformin and tolvaptan in ADPKD tolvaptan trials

Résumé fourni par la source

Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of kidney disease [1]. Tolvaptan, a vasopressin V2-receptor antagonist, is the only disease-modifying therapy available with proven efficacy in slowing disease progression. The anti-diabetic medication, metformin, has been theorised to be of potential benefit in ADPKD. Metformin activates 5 AMP-activated protein kinase, which negatively regulates the cystic fibrosis transmembrane conductance regulator and the mammalian target of rapamycin, both of which are implicated in the growth of cysts in ADPKD [2]. Two phase II trials [3, 4] have found metformin to be safe and tolerable in patients with ADPKD, with a non-significant slowing of estimated glomerular filtration rate (eGFR) decline and total kidney volume expansion. A phase III trial is currently underway to further define metformin’s role in ADPKD [5]. Given the established role of tolvaptan and the potential role of metformin in the management of ADPKD, the safety and efficacy of combined therapy are also of interest.

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