A combination of the vasopressin type 2 receptor antagonist tolvaptan and the somatostatin analogue pasireotide synergistically reduces cyst progression in a PKD1 mutant mouse model of autosomal dominant polycystic kidney disease (ADPKD). Both drugs indirectly inhibit adenylyl cyclase 6 activity, leading to a reduction in levels of 3', 5'-cAMP, which are decreased to those of wild-type controls by combination therapy. The dual therapy also results in smaller cystic and fibrotic volume, suggesting that it might be an effective treatment for ADPKD.