COMPOSITIONS AND METHODS TO TREAT NON-ALCOHOLIC FATTY LIVER DISEASES (NAFLD)
Provided herein are methods and combination therapies useful for the treatment of non-alcoholic fatty liver diseases (NAFLD). In particular, provided herein are methods and combination therapies for treating NAFLD by administering a combination therapy comprising (a) the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, and (b) an SGLT-2 inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or a GLP-1 receptor agonist, or a pharmaceutically acceptable salt or solvate thereof. Also provided are pharmaceutical compositions and pharmaceutical combinations comprising the compound of Formula (I) and an SGLT-2 inhibitor or a GLP-1 receptor agonist.
1 - 109 . (canceled)
110 . A method of treating non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof comprising administering to the subject
(a) a therapeutically effective amount of the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, and
(b) a therapeutically effective amount of an SGLT-2 inhibitor, or a pharmaceutically acceptable salt or solvate thereof.
111 . The method claim 110 , wherein the NAFLD is NASH.
112 . The method claim 110 , wherein the SGLT-2 inhibitor is selected from the group consisting of: empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin etabonate, serfliflozin etabonate, sotagliflozin, tofogliflozin, or a combination of two or more thereof.
113 . The method claim 110 , wherein the SGLT-2 inhibitor is empagliflozin.
114 . The method claim 110 , wherein the NAFLD activity score (NAS) following administration is 7 or less.
115 . The method claim 114 , wherein the NAS is 5 or less.
116 . The method claim 114 , wherein the NAS is 3 or less.
117 . The method claim 110 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose from about 0.1 to about 15 mg.
118 . The method claim 110 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose from about 0.1 to about 3 mg per day.
119 . The method claim 110 , wherein the compound of Formula (I) is in the form of a besylate salt.
120 . The method claim 110 , further comprising administering a GLP-1 receptor agonist selected from the group consisting of: liraglutide, dulaglutide, exenatide, taspoglutide, lixisenatide, albiglutide, semaglutide, GLP-1, or a combination of two or more thereof.
121 . The method claim 120 , wherein the GLP-1 receptor agonist is liraglutide.
122 . A method of treating fibrosis in a subject in need thereof comprising administering to the subject
(a) a therapeutically effective amount of the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, and
(b) a therapeutically effective amount of an SGLT-2 inhibitor, or a pharmaceutically acceptable salt or solvate thereof.
123 . The method claim 122 , wherein the treatment of fibrosis comprises a decrease in the stage of fibrosis.
124 . The method claim 123 , wherein the decrease in the stage of fibrosis is from stage 4 to stage 3, from stage 4 to stage 2, from stage 4 to stage 1, from stage 4 to stage 0, from stage 3 to stage 2, from stage 3 to stage 1, from stage 3 to stage 0, from stage 2 to stage 1, from stage 2 to stage 0, or from stage 1 to stage 0.
125 . The method claim 122 , wherein the SGLT-2 inhibitor is selected from the group consisting of: empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin etabonate, serfliflozin etabonate, sotagliflozin, tofogliflozin, or a combination of two or more thereof.
126 . The method claim 125 , wherein the SGLT-2 inhibitor is empagliflozin.
127 . The method claim 122 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose from about 0.1 to about 15 mg.
128 . The method claim 122 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, is administered at a dose from about 0.1 to about 3 mg per day.
129 . The method claim 122 , wherein the compound of Formula (I) is in the form of a besylate salt.
130 . The method claim 122 , further comprising administering a GLP-1 receptor agonist selected from the group consisting of: liraglutide, dulaglutide, exenatide, taspoglutide, lixisenatide, albiglutide, semaglutide, GLP-1, or a combination of two or more thereof.
131 . The method claim 130 , wherein the GLP-1 receptor agonist is liraglutide.