Drug combinations comprising a dgat inhibitor and a ppar-agonist

Abstract

The present invention relates to combinations of a DGAT inhibitor and a peroxisome proliferator-activator receptor (PPAR) agonist or a prodrug thereof. The invention further relates to methods for preparing such combinations, pharmaceutical compositions comprising said combinations as well as the use as a medicament of said combinations. The present invention also relates to novel DGAT inhibitors. The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicament of said compounds.

1 . A combination of a PPAR-α agonist or a prodrug thereof and a DGAT inhibitor wherein the DGAT inhibitor is selected from
 a) a compound having the formula 
 
       
         
           
           
               
               
           
         
       
       including any stereochemically isomeric form thereof, wherein
 A represents CH or N; 
 X represents O or NR x ; 
 the dotted line represents an optional bond in case A represents a carbon atom; 
 Y represents a direct bond; —NR x —C(═O)—; —C(═O)—NR x —; —NR x —C(═O)—Z—; 
 —NR x —C(═O)—Z—NR y —; —NR x —C(═O)—Z—NR y —C(═O)—; —NR x —C(═O)—Z—NR y —C(═O)—O—; 
 —NR x —C(═O)—Z—O—; —NR x —C(═O)—Z—O—C(═O)—; —NR x —C(═O)—Z—C(═O)—; 
 —NR x —C(═O)—Z—C(═O)—O—; —NR x —C(═O)—O—Z—C(═O)—; —NR x —C(═O)—O—Z—C(═O)—O—; 
 —NR x —C(═O)—O—Z—O—C(═O)—; —NR x —C(═O)—Z—C(═O)—NR y —; 
 —NR x —C(═O)—Z—NR y —C(═O)—NR y —; —C(═O)—Z—; —C(═O)—Z—O—; —C(═O)—NR x —Z—; 
 —C(═O)—NR x —Z—O—; —C(═O)—NR x —Z—C(═O)—O—; —C(═O)—NR x —Z—O—C(═O)—; 
 —C(═O)—NR x —O—Z—; —C(═O)—NR x —Z—NR y —; —C(═O)—NR x —Z—NR y —C(═O)—; 
 or —C(═O)—NR x —Z—NR y —C(═O)—O—; 
 Z represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with C 1-4 alkyloxy, C 1-4 alkylthio, hydroxyl, cyano or aryl; and wherein two hydrogen atoms attached to the same carbon atom in the definition of Z may optionally be replaced by C 1-6 alkanediyl; 
 R x  represents hydrogen or C 1-4 alkyl; 
 R y  represents hydrogen; C 1-4 alkyl optionally substituted with C 3-6 cycloalkyl or aryl or Het; C 2-4 alkenyl; or S(═O) p -aryl; 
 R 1  represents C 1-12 alkyl optionally substituted with cyano, C 1-4 alkyloxy, C 1-4 alkyl-oxyC 1-4 alkyloxy, C 3-6 cycloalkyl or aryl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-6 cycloalkyl; aryls; aryl 1 C 1-6 alkyl; Het 1 ; or Het 1 C 1-6 alkyl; provided that when Y represents —NR x —C(═O)—Z—; —NR x —C(═O)—Z—NR y ; —NR x —C(═O)—Z—C(═O)—NR y —; —C(═O)—Z—; —NR x —C(═O)—Z—NR y —C(═O)—NR y —; —C(═O)—NR x —Z—; —C(═O)—NR x —O—Z—; or —C(═O)—NR x —Z—NR y —; then R 1  may also represent hydrogen; 
 R 2  and R 3  each independently represent hydrogen; hydroxyl; carboxyl; halo; C 1-6 alkyl; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; or —S(═O) p —C 1-4 alkyl; 
 R 4  represents hydrogen; hydroxyl; carboxyl; halo; C 1-6 alkyl; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 6 R 5 N—C(═O)—; R 6 R 5 N—C 1-6 alkyl; C 3-6 cycloalkyl; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; or Het-O—; 
 R 5  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 8 R 7 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; aryl; or R 8 R 7 N—C(═O)—C 1-4 alkyl; 
 R 6  represents hydrogen or C 1-4 alkyl; 
 R 7  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
 R 8  represents hydrogen or C 1-4 alkyl; or 
 R 7  and R 8  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms each independently selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
 R 9  represents hydrogen; halo; C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
 aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
 aryl 1  represents phenyl, naphthalenyl or fluorenyl; each of said phenyl, naphthalenyl or fluorenyl optionally substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, 
 C 1-4  alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6  alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; amino; mono- or di(C 1-6 alkyl)amino; R 6 R 5 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—; aryl-C(═O)—C 1-4 alkyl; Het; HetC 1-4 alkyl; Het-C(═O)—; Het-C(═O)—C 1-4 alkyl; and Het-O—; 
 Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyl-oxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
 Het 1  represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6  alkyloxy optionally substituted with C 1-4  alkyloxy; C 1-6  alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; amino; mono- or di(C 1-6 alkyl)amino; R 6 R 5 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—; aryl-C(═O)—C 1-4 alkyl; Het; HetC 1-4 alkyl; Het-C(═O)—; Het-C(═O)—C 1-4 alkyl; and Het-O—; 
 p represents 1 or 2; 
 a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof; 
 b) a compound having the formula 
 
       
         
           
           
               
               
           
         
         including any stereochemically isomeric form thereof, wherein 
         A represents CH or N; 
         the dotted line represents an optional bond in case A represents a carbon atom; 
         X represents —NR x —C(═O)—; —Z—C(═O)—; —Z—NR x —C(═O)—; —S(═O) p —; C(═S)—; 
         —NR x —C(═S)—; —Z—C(═S)—; —Z—NR x —C(═S)—; —O—C(═O)—; or —C(═O)—C(═O)—; 
         Z represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with hydroxyl or amino; and wherein two hydrogen atoms attached to the same carbon atom in C 1-6 alkanediyl may optionally be replaced by C 1-6 alkanediyl; 
         R x  represents hydrogen or C 1-4 alkyl; 
         R 1 — represents a 5-membered monocyclic heterocycle containing at least 2 heteroatoms; 
         a 6-membered aromatic monocyclic heterocycle; or a 5-membered heterocycle containing at least 2 heteroatoms fused with phenyl, cyclohexyl or a 5- or 6-membered heterocycle; wherein each of said heterocycles may optionally be substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)-aminocarbonyl; C 1-6 alkylcarbonyl; amino; mono- or di(C 1-6 alkyl)amino; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkyl-C 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—; aryl-C(═O)—C 1-4 alkyl; Het; HetC 1-4 alkyl; Het-C(═O)—; Het-C(═O)—C 1-4 alkyl; and Het-O—; 
         R 2  represents R 3 ; 
         R 3  represents C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with hydroxy; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 5 R 4 N—C(═O)—; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyk C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         R 4  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 7 R 6 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; aryl; or R 7 R 6 N—C(═O)—C 1-4 alkyl; 
         R 5  represents hydrogen or C 1-4 alkyl; 
         R 6  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
         R 7  represents hydrogen or C 1-4 alkyl; or 
         R 6  and R 7  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
         R 8  represents hydrogen halo C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
         aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyl-oxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl 
         p represents 1 or 2; 
         a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof; 
         c) a compound having the formula 
       
       
         
           
           
               
               
           
         
         including any stereochemically isomeric form thereof, wherein 
         A represents CH or N; 
         the dotted line represents an optional bond in case A represents a carbon atom; 
         X represents O—C(═O)—; —C(═O)—C(═O)—; —NR x —C(═O)—; —Z—C(═O)—; —Z—NR x —C(═O)—; —C(═O)—Z—; —NR x —C(═O)—Z—; C(═S)—; —S(═O) p —; —NR x —C(═S)—; —Z—C(═S)—; —Z—NR x —C(═S)—; —C(═S)—Z—; or —NR x —C(═S)—Z—; 
         Z represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with hydroxyl or amino; and wherein two hydrogen atoms attached to the same carbon atom in C 1-6 alkanediyl may optionally be replaced by C 1-6 alkanediyl; 
         R x  represents hydrogen or C 1-4 alkyl; 
         Y represents C(═O)—NR x — or —NR x —C(═O)—; 
         R 1  represents adamantanyl; C 3-6 cycloalkyl; aryl 1  or Het 1 ; 
         R 2  represents hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl or 6-membered aromatic heterocycle containing 1 or 2 N atoms may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6  alkyl optionally substituted with hydroxy; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 4 R 3 N—C(═O)—; R 4 R 3 N—C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         R 3  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 6 R 5 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; Het-C 1-4 alkyl; aryl; or R 6 R 5 N—C(═O)—C 1-4 alkyl; 
         R 4  represents hydrogen or C 1-4 alkyl; 
         R 5  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
         R 6  represents hydrogen or C 1-4 alkyl; or 
         R 5  and R 6  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms each independently selected from the group consisting of O, S, S(═O) p  Of and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
         R 7  represents hydrogen; halo; C 1-4 alkyl 7  or C 1-4 alkyl substituted with hydroxyl; 
         aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         aryl 1  represents phenyl, naphthalenyl or fluorenyl; each of said phenyl, naphthalenyl or fluorenyl optionally substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4  alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6  alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 4 R 3 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         Het 1  represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 4 R 3 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         p represents 1 or 2; 
         a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof; 
         or 
         d) a compound having the formula 
       
       
         
           
           
               
               
           
         
         including any stereochemically isomeric form thereof, wherein 
         A represents CH or N; 
         the dotted line represents an optional bond in case A represents a carbon atom; 
         X represents C(═O)—; —O—C(═O)—; —C(═O)—C(═O)—; —NR x —C(═O)—; —Z 1 —C(═O)—; —Z 1 —NR x —C(═O)—; —C(═O)—Z 1 —; —NR x —C(═O)—Z 1 —; —S(═O) p —; C(═S)—; —NR x —C(═S)—; —Z 1 —C(═S)—; —Z 1 —NR x —C(═S)—; —C(═S)—Z 1 —; or —NR x —C(═S)—Z 1 —; 
         Z 1  represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with hydroxyl or amino; and wherein two hydrogen atoms attached to the same carbon atom in C 1-6 alkanediyl may optionally be replaced by C 1-6 alkanediyl; 
         Y represents NR x —C(═O)—Z 2 —; —NR x —C(═O)—Z 2 —NR y —; —NR x —C(═O)—Z 2 —NR y —C(═O)—; —NR x —C(═O)—Z 2 —NR y —C(═O)—O—; —NR x —C(═O)—Z 2 -0—; —NR x —C(═O)—Z 2 —O—C(═O)—; —NR x —C(═O)—Z 2 —C(═O)—; —NR x —C(═O)—Z 2 —C(═O)—O—; —NR x —C(═O)—O—Z 2 —C(═O)—; —NR x —C(═O)—O—Z 2 —C(═O)—O—; —NR x —C(═O)—O—Z 2 —O—C(═O)—; —NR x —C(═O)—Z 2 —C(═O)—NR y —; —NR x —C(═O)—Z 2 —NR y —C(═O)—NR y —; —C(═O)—Z 2 —; —C(═O)—Z 2 —O—; —C(═O)—NR x —Z 2 —; —C(═O)—NR x —Z 2 —O—; —C(═O)—NR x —Z 2 —C(═O)—O—; —C(═O)—NR x —Z 2 —O—C(═O)—; —C(═O)—NR x —O—Z 2 —; —C(═O)—NR x —Z 2 —NR y —; —C(═O)—NR x —Z 2 —NR y —C(═O)—; or —C(═O)—NR x —Z 2 —NR y —C(═O)—O—; 
         Z 2  represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with C 1-4 alkyloxy, C 1-4 alkylthio, hydroxyl, cyano or aryl; and wherein two hydrogen atoms attached to the same carbon atom in the definition of Z 2  may optionally be replaced by C 1-6 alkanediyl; 
         R x  represents hydrogen or C 1-4 alkyl; 
         R y  represents hydrogen; C 1-4 alkyl optionally substituted with C 3-6 cycloalkyl or aryl or Het; C 2-4 alkenyl; or S(═O) p -aryl; 
         R 1  represents C 1-12 alkyl optionally substituted with cyano, C 1-4 alkyloxy, C 1-4 alkyl-oxyC 1-4 alkyloxy, C 3-6 cycloalkyl or aryl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-6 cycloalkyl; adamantanyl; aryls; aryl 1 C 1-6 alkyl; Het 1 ; or Het 1 C 1-6 alkyl; provided that when Y represents —NR x —C(═O)—Z 2 —; —NR x —C(═O)—Z 2 —NR y ; —NR x —C(═O)—Z 2 —C(═O)—NR y —; —C(═O)—Z 2 —; —NR x —C(═O)—Z 2 —NR y —C(═O)—NR y —; —C(═O)—NR x —Z 2 —; —C(═O)—NR x —O—Z 2 —; or —C(═O)—NR x —Z 2 —NR y —; then R 1  may also represent hydrogen; 
         R 2  represents hydrogen; C 1-12 alkyl; C 2-6 alkenyl; or R 3 ; 
         R 3  represents C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl or 6-membered aromatic heterocycle containing 1 or 2 N atoms may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with hydroxy; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 5 R 4 N—C(═O)—; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         R 4  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 7 R 6 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; Het-C 1-4 alkyl; aryl; or R 7 R 6 N—C(═O)—C 1-4 alkyl; 
         R 5  represents hydrogen or C 1-4 alkyl; 
         R 6  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
         R 7  represents hydrogen or C 1-4 alkyl; or 
         R 6  and R 7  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms each independently selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
         R 8  represents hydrogen; halo; C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
         aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         aryl 1  represents phenyl, naphthalenyl or fluorenyl; each of said phenyl, naphthalenyl or fluorenyl optionally substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         Het 1  represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         p represents 1 or 2; 
         provided that if X represents O—C(═O)—, then R 2  represents R 3 ; 
         a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof 
       
     
     
         2 . The combination according to  claim 1  wherein the DGAT inhibitor has the following formula 
       
         
           
           
               
               
           
         
         including any stereochemically isomeric form thereof, wherein 
         A represents CH or N; 
         X represents O or NR x ; 
         the dotted line represents an optional bond in case A represents a carbon atom; 
         Y represents a direct bond; —NR x —C(═O)—; —C(═O)—NR x —; —NR x —C(═O)—Z—; —NR x —C(═O)—Z—NR y —; —NR x —C(═O)—Z—NR y —C(═O)—; —NR x —C(═O)—Z—NR y —C(═O)—O—; —NR x —C(═O)—Z—O—; —NR x —C(═O)—Z—O—C(═O)—; —NR x —C(═O)—Z—C(═O)—; —NR x —C(═O)—Z—C(═O)—O—; —NR x —C(═O)—O—Z—C(═O)—; —NR x —C(═O)—O—Z—C(═O)—O—; —NR x —C(═O)—O—Z—O—C(═O)—; —NR x —C(═O)—Z—C(═O)—NR y —; —NR x —C(═O)—Z—NR y —C(═O)—NR y —; —C(═O)—Z—; —C(═O)—Z—O—; —C(═O)—NR x —Z—; —C(═O)—NR x —Z—O—; —C(═O)—NR x —Z—C(═O)—O—; —C(═O)—NR x —Z—O—C(═O)—; —C(═O)—NR x —O—Z—; —C(═O)—NR x —Z—NR y —; —C(═O)—NR x —Z—NR y —C(═O)—; or —C(═O)—NR x —Z—NR y —C(═O)—O—; 
         Z represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with C 1-4 alkyloxy, C 1-4 alkylthio, hydroxyl, cyano or aryl; and wherein two hydrogen atoms attached to the same carbon atom in the definition of Z may optionally be replaced by C 1-6 alkanediyl; 
         R x  represents hydrogen or C 1-4 alkyl; 
         R y  represents hydrogen; C 1-4 alkyl optionally substituted with C 3-6 cycloalkyl or aryl or Het; C 2-4 alkenyl; or S(═O) p -aryl; 
         R 1  represents C 1-12 alkyl optionally substituted with cyano, C 1-4 alkyloxy, C 1-4 alkyl-oxyC 1-4 alkyloxy, C 3-6 cycloalkyl or aryl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-6 cycloalkyl; aryls; aryl 1  C 1-6 alkyl; Het 1 ; or Het'C 1-6 alkyl; provided that when Y represents —NR x —C(═O)—Z—; —NR x —C(═O)—Z—NR y ; —NR x —C(═O)—Z—C(═O)—NR y —; —C(═O)—Z—; —NR x —C(═O)—Z—NR y —C(═O)—NR y —; —C(═O)—NR x —Z—; —C(═O)—NR x —O—Z—; or —C(═O)—NR x —Z—NR y —; then R 1  may also represent hydrogen; 
         R 2  and R 3  each independently represent hydrogen; hydroxyl; carboxyl; halo; C 1-6 alkyl; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; or —S(═O) p —C 1-4 alkyl; 
         R 4  represents hydrogen; hydroxyl; carboxyl; halo; C 1-6 alkyl; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 6 R 5 N—C(═O)—; R 6 R 5 N—C 1-6 alkyl; C 3-6 cycloalkyl; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; or Het-O—; 
         R 5  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 8 R 7 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; aryl; or R 8 R 7 N—C(═O)—C 1-4 alkyl; 
         R 6  represents hydrogen or C 1-4 alkyl; 
         R 7  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
         R 8  represents hydrogen or C 1-4 alkyl; or 
         R 7  and R 8  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms each independently selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
         R 9  represents hydrogen; halo; C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
         aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         aryl 1  represents phenyl, naphthalenyl or fluorenyl; each of said phenyl, naphthalenyl or fluorenyl optionally substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4  alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6  alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; amino; mono- or di(C 1-6 alkyl)amino; R 6 R 5 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—; aryl-C(═O)—C 1-4 alkyl; Het; HetC 1-4 alkyl; Het-C(═O)—; Het-C(═O)—C 1-4 alkyl; and Het-O—; 
         Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyl-oxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         Het 1  represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6  alkyloxy optionally substituted with C 1-4  alkyloxy; C 1-6  alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; amino; mono- or di(C 1-6 alkyl)amino; R 6 R 5 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—; aryl-C(═O)—C 1-4 alkyl; Het; HetC 1-4 alkyl; Het-C(═O)—; Het-C(═O)—C 1-4 alkyl; and Het-O—; 
         p represents 1 or 2; 
         a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof 
       
     
     
         3 . The combination according to  claim 1  wherein the DGAT inhibitor has the following formula 
       
         
           
           
               
               
           
         
         including any stereochemically isomeric form thereof, wherein 
         A represents CH or N; 
         the dotted line represents an optional bond in case A represents a carbon atom; 
         X represents —NR x —C(═O)—; —Z—C(═O)—; —Z—NR x —C(═O)—; —S(═O) p —; C(═S)—; —NR x —C(═S)—; —Z—C(═S)—; —Z—NR x —C(═S)—; —O—C(═O)—; or —C(═O)—C(═O)—; 
         Z represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with hydroxyl or amino; and wherein two hydrogen atoms attached to the same carbon atom in C 1-6 alkanediyl may optionally be replaced by C 1-6 alkanediyl; 
         R x  represents hydrogen or C 1-4 alkyl; 
         R 1  represents a 5-membered monocyclic heterocycle containing at least 2 heteroatoms; a 6-membered aromatic monocyclic heterocycle; or a 5-membered heterocycle containing at least 2 heteroatoms fused with phenyl, cyclohexyl or a 5- or 6-membered heterocycle; wherein each of said heterocycles may optionally be substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)-aminocarbonyl; C 1-6 alkylcarbonyl; amino; mono- or di(C 1-6 alkyl)amino; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkyl-C 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—; aryl-C(═O)—C 1-4 alkyl; Het; HetC 1-4 alkyl; Het-C(═O)—; Het-C(═O)—C 1-4 alkyl; and Het-O—; 
         R 2  represents R 3 ; 
         R 3  represents C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with hydroxy; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 5 R 4 N—C(═O)—; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         R 4  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 7 R 6 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; aryl; or R 7 R 6 N—C(═O)—C 1-4 alkyl; 
         R 5  represents hydrogen or C 1-4 alkyl; 
         R 6  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
         R 7  represents hydrogen or C 1-4 alkyl; or 
         R 6  and R 7  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
         R 8  represents hydrogen halo; C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
         aryl represents phenyl or phenyl substituted with at least one substituent, one, two, three, four or five substituents, each substituent independently being each substituent independently being selected the group consisting of from hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyl-oxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl 
         p represents 1 or 2; 
         a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 
       
     
     
         4 . The combination according to  claim 1  wherein the DGAT inhibitor has the following formula 
       
         
           
           
               
               
           
         
         including any stereochemically isomeric form thereof, wherein 
         A represents CH or N; 
         the dotted line represents an optional bond in case A represents a carbon atom; 
         X represents O—C(═O)—; —C(═O)—C(═O)—; —NR x —C(═O)—; —Z—C(═O)—; —Z—NR x —C(═O)—; —C(═O)—Z—; —NR x —C(═O)—Z—; C(═S)—; —S(═O) p —; —NR x —C(═S)—; —Z—C(═S)—; —Z—NR x —C(═S)—; —C(═S)—Z—; or —NR x —C(═S)—Z—; 
         Z represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with hydroxyl or amino; and wherein two hydrogen atoms attached to the same carbon atom in C 1-6 alkanediyl may optionally be replaced by C 1-6 alkanediyl; 
         R x  represents hydrogen or C 1-4 alkyl; 
         Y represents C(═O)—NR x — or —NR x —C(═O)—; 
         R 1  represents adamantanyl, C 3-6 cycloalkyl; aryl 1  or Het 1 ; 
         R 2  represents hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl or 6-membered aromatic heterocycle containing 1 or 2 N atoms may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with hydroxy; polyhaloC 1-6  alkyl; C 1-6  alkyloxy optionally substituted with C 1-4  alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 4 R 3 N—C(═O)—; R 4 R 3 N—C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; et-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         R 3  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 6 R 5 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; Het-C 1-4 alkyl; aryl; or R 6 R 5 N—C(═O)—C 1-4 alkyl; 
         R 4  represents hydrogen or C 1-4 alkyl; 
         R 5  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
         R 6  represents hydrogen or C 1-4 alkyl; or 
         R 5  and R 6  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms each independently selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
         R 7  represents hydrogen halo; C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
         aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         aryl 1  represents phenyl, naphthalenyl or fluorenyl; each of said phenyl, naphthalenyl or fluorenyl optionally substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 4 R 3 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
         Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
         Het 1  represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio;
 polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 4 R 3 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
 
         p represents 1 or 2; 
         a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof 
       
     
     
         5 . The combination according to  claim 1  wherein the DGAT inhibitor has the following formula 
       
         
           
           
               
               
           
         
       
       including any stereochemically isomeric form thereof, wherein
 A represents CH or N; 
 the dotted line represents an optional bond in case A represents a carbon atom; 
 X represents C(═O)—; —O—C(═O)—; —C(═O)—C(═O)—; —NR x —C(═O)—; —Z 1 —C(═O)—; —Z 1 —NR x —C(═O)—; —C(═O)—Z 1 —; —NR x —C(═O)—Z 1 —; —S(═O) p —; C(═S)—; —NR x —C(═S)—; —Z 1 —C(═S)—; —Z 1 —NR x —C(═S)—; —C(═S)—Z 1 —; or —NR x —C(═S)—Z 1 —; 
 Z 1  represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with hydroxyl or amino; and wherein two hydrogen atoms attached to the same carbon atom in C 1-6 alkanediyl may optionally be replaced by C 1-6 alkanediyl; 
 Y represents NR x —C(═O)—Z 2 —; —NR x —C(═O)—Z 2 —NR y —; —NR x —C(═O)—Z 2 —NR y —C(═O)—; —NR x —C(═O)—Z 2 —NR y —C(═O)—O—; —NR x —C(═O)—Z 2 -0—; —NR x —C(═O)—Z 2 —O—C(═O)—; —NR x —C(═O)—Z 2 —C(═O)—; —NR x —C(═O)—Z 2 —C(═O)—O—; —NR x —C(═O)—O—Z 2 —C(═O)—; —NR x —C(═O)—O—Z 2 —C(═O)—O—; —NR x —C(═O)—O—Z 2 —O—C(═O)—; —NR x —C(═O)—Z 2 —C(═O)—NR y —; —NR x —C(═O)—Z 2 —NR y —C(═O)—NR y —; —C(═O)—Z 2 —; —C(═O)—Z 2 —O—; —C(═O)—NR x —Z 2 —; —C(═O)—NR x —Z 2 —O—; —C(═O)—NR x —Z 2 —C(═O)—O—; —C(═O)—NR x —Z 2 —O—C(═O)—; —C(═O)—NR x —O—Z 2 —; —C(═O)—NR x —Z 2 —NR y —; —C(═O)—NR x —Z 2 —NR y —C(═O)—; or —C(═O)—NR x —Z 2 —NR y —C(═O)—O—; 
 Z 2  represents a bivalent radical selected from C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl; wherein each of said C 1-6 alkanediyl, C 2-6 alkenediyl or C 2-6 alkynediyl may optionally be substituted with C 1-4 alkyloxy, C 1-4 alkylthio, hydroxyl, cyano or aryl; and wherein two hydrogen atoms attached to the same carbon atom in the definition of Z 2  may optionally be replaced by C 1-6 alkanediyl; 
 R x  represents hydrogen or C 1-4 alkyl; 
 R y  represents hydrogen; C 1-4 alkyl optionally substituted with C 3-6 cycloalkyl or aryl or Het; C 2-4 alkenyl; or S(═O) p -aryl; 
 R 1  represents C 1-12 alkyl optionally substituted with cyano, C 1-4 alkyloxy, C 1-4 alkyl-oxyC 1-4 alkyloxy, C 3-6 cycloalkyl or aryl; C 2-6 alkenyl; C 2-6 alkynyl; C 3-6 cycloalkyl; adamantanyl; aryls; aryl 1 C 1-6 alkyl; Hee; or Het 1 C 1-6 alkyl; provided that when Y represents —NR x —C(═O)—Z 2 —; —NR x —C(═O)—Z 2 —NR y ; —NR x —C(═O)—Z 2 —C(═O)—NR y —; —C(═O)—Z 2 —; —NR x —C(═O)—Z 2 —NR y —C(═O)—NR y —; —C(═O)—NR x —Z 2 —; —C(═O)—NR x —O—Z 2 —; or —C(═O)—NR x —Z 2 —NR y —; then RI- may also represent hydrogen; 
 R 2  represents hydrogen, C 1-12 alkyl, C 2-6 alkenyl or R 3 ; 
 R 3  represents C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl or 6-membered aromatic heterocycle containing 1 or 2 N atoms may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with hydroxy; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhalo-C 1-6 alkyloxy; C 1-6 alkyloxycarbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and C 1-4 alkylcarbonylamino; —S(═O) p —C 1-4 alkyl; R 5 R 4 N—C(═O)—; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
 R 4  represents hydrogen; C 1-4 alkyl optionally substituted with hydroxyl or C 1-4 alkyloxy; R 7 R 6 N—C 1-4 alkyl; C 1-4 alkyloxy; Het; Het-C 1-4 alkyl; aryl; or R 7 R 6 N—C(═O)—C 1-4 alkyl; 
 R 5  represents hydrogen or C 1-4 alkyl; 
 R 6  represents hydrogen; C 1-4 alkyl; or C 1-4 alkylcarbonyl; 
 R 7  represents hydrogen or C 1-4 alkyl; or 
 R 6  and R 7  may be taken together with the nitrogen to which they are attached to form a saturated monocyclic 5, 6 or 7-membered heterocycle which may further contain one or more heteroatoms each independently selected from the group consisting of O, S, S(═O) p  and N; and which heterocycle may optionally be substituted with C 1-4 alkyl; 
 R 8  represents hydrogen halo; C 1-4 alkyl; or C 1-4 alkyl substituted with hydroxyl; 
 aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
 aryl 1  represents phenyl, naphthalenyl or fluorenyl; each of said phenyl, naphthalenyl or fluorenyl optionally substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4  alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
 Het represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with C 1-4 alkyloxy, amino or mono- or di(C 1-4 alkyl)amino; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-4 alkyl)amino; and —S(═O) p —C 1-4 alkyl; 
 Het 1  represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; or a bicyclic or tricyclic non-aromatic or aromatic heterocycle containing at least one heteroatom each independently selected from the group consisting of O, S, S(═O) p  and N; said monocyclic heterocycle or said bi- or tricyclic heterocycle optionally being substituted with at least one substituent, each substituent independently being selected from the group consisting of hydroxyl; oxo; carboxyl; halo; C 1-6 alkyl optionally substituted with carboxyl, C 1-4 alkyloxycarbonyl or aryl-C(═O)—; hydroxyC 1-6 alkyl optionally substituted with aryl or aryl-C(═O)—; polyhaloC 1-6 alkyl; C 1-6 alkyloxy optionally substituted with C 1-4 alkyloxy; C 1-6 alkylthio; polyhaloC 1-6 alkyloxy; C 1-6 alkyloxy-carbonyl wherein C 1-6 alkyl may optionally be substituted with aryl; cyano; aminocarbonyl; mono- or di(C 1-4 alkyl)aminocarbonyl; C 1-6 alkylcarbonyl; nitro; amino; mono- or di(C 1-6 alkyl)amino; R 5 R 4 N—C 1-6 alkyl; C 3-6 cycloalkyl-NR x —; aryl-NR x —; Het-NR x —; C 3-6 cycloalkylC 1-4 alkyl-NR x —; arylC 1-4 alkyl-NR x —; HetC 1-4 alkyl-NR x —; —S(═O) p —C 1-4 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkylC 1-4 alkyl; C 3-6 cycloalkyl-C(═O)—; aryl; aryloxy; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; aryl-C(═O)—; Het; HetC 1-4 alkyl; Het-C(═O)—C 1-4 alkyl; Het-C(═O)—; and Het-O—; 
 p represents 1 or 2; 
 provided that if X represents O—C(═O)—, then R 2  represents R 3 ; 
 a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof 
 
     
     
         6 . The combination according to  claim 4  wherein the DGAT inhibitor is selected from:
 4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)phenyl]-benzamide; 
 4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]hydroxyacetyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)phenyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)phenyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-[[4-(methylsulfonyl)-1-piperazinyl]methyl]phenyl]acetyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)phenyl]-benzamide; 
 4-[4-[[4-[(4-acetyl-1-piperazinyl)methyl]-2,6-dichlorophenyl]acetyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)phenyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-[(4-ethyl-1-piperazinyl)methyl]phenyl]acetyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)phenyl]-benzamide; 
 including any stereochemically isomeric form thereof; 
 a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 
 
     
     
         7 . The combination according to  claim 5  wherein the DGAT inhibitor is selected from:
 N4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]phenyl]-4-methoxy-benzeneacetamide; 
 4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]-N-[[3-(1-pyrrolidinyl)phenyl]methyl]-benzamide; 
 4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]hydroxyacetyl]-1-piperazinyl]-N-[[3-(1-pyrrolidinyl)phenyl]methyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]-N-[(3,5-dimethoxyphenyl)methyl]-benzamide; 
 4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]-N-[(3,5-dimethoxyphenyl)methyl]-benzamide; 
 4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]hydroxyacetyl]-1-piperazinyl]-N-[(3,5-dimethoxyphenyl)methyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-[(4-ethyl-1-piperazinyl)methyl]phenyl]acetyl]-1-piperazinyl]-N-[(3,5-dimethoxyphenyl)methyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-[(4-ethyl-1-piperazinyl)methyl]phenyl]acetyl]-1-piperazinyl]-N-[[3-(1-pyrrolidinyl)phenyl]methyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-[[4-(methylsulfonyl)-1-piperazinyl]methyl]phenyl]acetyl]-1-piperazinyl]-N-[(3,5-dimethoxyphenyl)methyl]-benzamide; 
 4-[4-[[4-[(4-acetyl-1-piperazinyl)methyl]-2,6-dichlorophenyl]acetyl]-1-piperazinyl]-N-[[3-(1-pyrrolidinyl)phenyl]methyl]-benzamide; 
 4-[4-[[2,6-dichloro-4-[[4-(methylsulfonyl)-1-piperazinyl]methyl]phenyl]acetyl]-1-piperazinyl]-N-[[3-(1-pyrrolidinyl)phenyl]methyl]-benzamide; 
 4-[4-[[4-[(4-acetyl-1-piperazinyl)methyl]-2,6-dichlorophenyl]acetyl]-1-piperazinyl]-N-[(3,5-dimethoxyphenyl)methyl]-benzamide; 
 N-[4-[4-[[2-chloro-4-(1-pyrrolidinylmethyl)phenyl]hydroxyacetyl]-1-piperazinyl]phenyl]-4-methoxy-benzeneacetamide; 
 N4-[4-[[2,6-dichloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]phenyl]-4-methoxy-benzeneacetamide; 
 4-[4-[[2,6-dichloro-4-(1-pyrrolidinylmethyl)phenyl]acetyl]-1-piperazinyl]-N-[[3-(1-pyrrolidinyl)phenyl]methyl]-benzamide; 
 including any stereochemically isomeric form thereof; 
 a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 
 
     
     
         8 . The combination according to  claim 1  wherein the PPAR-α agonist or a prodrug thereof is a fibrate. 
     
     
         9 . The combination according to  claim 8  wherein the fibrate is fenofibrate. 
     
     
         10 . A combination according to  claim 1  for reducing food intake, for reducing weight, for suppressing appetite, for inducing satiety; or for the treatment or prevention, in particular treatment, of metabolic disorders, such as obesity and/or obesity related disorders (including, but not limited to, peripheral vascular disease, cardiac failure, myocardial ischaemia, cerebral ischaemia, cardiac myopathies), diabetes, in particular type II diabetes mellitus, and/or complications arising therefrom (such as retinopathy, neuropathy, nephropathy), syndrome X, insulin resistance, impaired glucose tolerance, conditions of impaired fasting glucose, hypoglycemia, hyperglycemia, hyperuricemia, hyperinsulinemia, pancreatitis, hypercholesterolemia, hyperlipidemia, dyslipidemia, mixed dyslipidemia, hypertriglyceridemia, nonalcoholic fatty liver disease, fatty liver, increased mesenteric fat, non-alcoholic steatohepatitis, liver fibrosis, metabolic acidosis, ketosis, dysmetabolic syndrome; dermatological conditions such as acne, psoriasis; cardiovascular diseases, such as atherosclerosis, arteriosclerosis, acute heart failure, congestive heart failure, coronary artery disease, cardiomyopathy, myocardial infarction, angina pectoris, hypertension, hypotension, stroke, ischemia, ischemic reperfusion injury, aneurysm, restenosis or vascular stenosis; alzheimer's disease; neoplastic diseases, such as solid tumors, skin cancer, melanoma, lymphoma or endothelial cancers, e.g., breast cancer, lung cancer, colorectal cancer, stomach cancer, other cancers of the gastrointestinal tract (e.g., esophageal cancer or pancreatic cancer), prostate cancer, kidney cancer, liver cancer, bladder cancer, cervical cancer, uterine cancer, testicular cancer or ovarian cancer. 
     
     
         11 . The combination according to  claim 10  for reducing food intake, for reducing weight, for suppressing appetite, for inducing satiety; for the treatment or prevention of obesity and/or obesity related disorders, diabetes or cardiovascular diseases. 
     
     
         12 - 15 . (canceled) 
     
     
         16 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a combination according to  claim 1 .