761:
Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-4 inhibitors with pancreatic cancer. In a joint letter to the New
England Journal of Medicines, the agencies stated that "Both agencies agree that assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and in the media, are inconsistent with the current data. The FDA and the EMA have not reached a final conclusion at this time regarding such a causal relationship. Although the totality of the data that have been reviewed provides reassurance, pancreatitis will continue to be considered a risk associated with these drugs until more data are available; both agencies continue to investigate this safety signal."
542:
519:
40:
31:
2340:
760:
There have been case reports of pancreatitis associated with DPP-4 inhibitors. A group at UCLA reported increased pre-cancerous pancreatic changes in rats and in human organ donors who had been treated with DPP-4 inhibitors. In response to these reports, the United States FDA and the
European
1052:"Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors"
872:"Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum"
719:
by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of
Langerhans in the pancreas.
1177:
1003:"Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin"
2257:
2172:
2237:
2217:
2162:
2212:
2207:
2202:
2197:
2192:
611:
150:
2182:
1170:
757:
Adverse effects observed in clinical trials include nausea, hypoglycemia, tremor, headache and dizziness. Rare cases of hepatoxicity have been reported.
679:
107:
770:
1163:
1155:
1874:
1644:
976:
663:
InChI=1S/C17H25N3O2/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16/h12-14,19,22H,1-8,10-11H2/t12?,13?,14-,16?,17?/m0/s1
1894:
70:
635:
2360:
797:
1753:
716:
828:"Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes"
2290:
1380:
2375:
2147:
686:
655:
2307:
1850:
1397:
1185:
1605:
1596:
1330:
312:
195:
88:
1432:
387:
1292:
1334:
537:
438:
1983:
498:
487:
2390:
2330:
1945:
1811:
1344:
2252:
2152:
2142:
738:
102:
962:
514:
2227:
2132:
726:
2295:
2267:
2242:
2222:
2187:
2167:
2157:
2137:
2127:
2050:
1385:
712:
136:
52:
2272:
2232:
2055:
795:
775:
746:
251:
1532:
1099:
Egan AG, Blind E, Dunder K, de Graeff PA, Hummer BT, Bourcier T, et al. (February 2014).
2380:
2365:
2262:
2247:
2177:
427:
378:
1144:
342:
2385:
2122:
801:
447:
279:
1001:
Matveyenko AV, Dry S, Cox HI, Moshtaghian A, Gurlo T, Galasso R, et al. (July 2009).
8:
1187:
333:
143:
541:
518:
1308:
1076:
1051:
1050:
Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC (July 2013).
1027:
1002:
939:
912:
888:
871:
704:
118:
2370:
1823:
1469:
1356:
1242:
1122:
1081:
1032:
944:
893:
849:
210:
826:
Ahrén B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A (May 2004).
367:
2110:
1326:
1288:
1112:
1071:
1063:
1022:
1014:
934:
924:
883:
839:
796:
WHO International
Working Group for Drug Statistics Methodology (August 27, 2008).
708:
622:
554:
233:
174:
163:
2344:
1283:
1265:
271:
261:
241:
2301:
2045:
1710:
1639:
1391:
1340:
1247:
1237:
1217:
1195:
2354:
2091:
2070:
2065:
2060:
2040:
2035:
2030:
2025:
2020:
1914:
1670:
1629:
1517:
1512:
1502:
1497:
1303:
530:
22:
1919:
1899:
1801:
1791:
1786:
1675:
1649:
1617:
1577:
1555:
1550:
1545:
1522:
1507:
1487:
1473:
1199:
1126:
1085:
1036:
948:
853:
844:
827:
169:
158:
897:
800:. WHO Collaborating Centre for Drug Statistics Methodology. Archived from
1909:
1904:
1889:
1884:
1879:
1835:
1829:
1796:
1781:
1771:
1766:
1761:
1739:
1734:
1729:
1720:
1705:
1690:
1680:
1659:
1634:
1582:
1540:
1492:
1482:
1298:
1117:
1100:
407:
39:
2086:
1973:
1963:
1958:
1953:
1869:
1864:
1859:
1700:
1685:
1654:
1459:
929:
587:
418:
267:
80:
1067:
1018:
2096:
2011:
2001:
1968:
1819:
1776:
1695:
1454:
1441:
742:
353:
292:
179:
74:
1996:
1991:
1449:
1101:"Pancreatic safety of incretin-based drugs--FDA and EMA assessment"
467:
398:
1049:
610:
1213:
1191:
913:"Vildagliptin: a new oral treatment for type 2 diabetes mellitus"
825:
106:
749:(Eucreas by Novartis) as an oral treatment for type-2 diabetes.
1565:
478:
297:
30:
1569:
601:
503:
1000:
458:
711:
class of drugs. Vildagliptin inhibits the inactivation of
1810:
798:"ATC/DDD Classification (FINAL): New ATC 5th level codes"
1098:
869:
725:
Vildagliptin has been shown to reduce hyperglycemia in
2328:
832:
The
Journal of Clinical Endocrinology and Metabolism
741:
has also approved a combination of vildagliptin and
386:
703:and others, is an oral anti-hyperglycemic agent (
2352:
870:Mentlein R, Gallwitz B, Schmidt WE (June 1993).
771:Development of dipeptidyl peptidase-4 inhibitors
366:
910:
627:Freely Soluble in water mg/mL (20 °C)
341:
963:"EU approves Novartis's Eucreas diabetes drug"
955:
1171:
732:
1212:
225:In general: ℞ (Prescription only)
1178:
1164:
865:
863:
540:
517:
426:
38:
29:
1116:
1075:
1026:
938:
928:
887:
843:
643:N#C4N(C(=O)CNC13CC2CC(C1)CC(O)(C2)C3)CCC4
446:
709:dipeptidyl peptidase-4 (DPP-4) inhibitor
911:Mathieu C, Degrande E (December 2008).
860:
821:
819:
513:
406:
2353:
531:
217:
204:
97:
1420:
1211:
1159:
486:
79:
1198:, and other drugs used in diabetes (
1151:. U.S. National Library of Medicine.
816:
722:It was approved by the EMA in 2007.
173:
162:
2168:Glibenclamide (glyburide)/metformin
2148:Dapagliflozin/saxagliptin/metformin
1105:The New England Journal of Medicine
917:Vascular Health and Risk Management
466:
357:
13:
889:10.1111/j.1432-1033.1993.tb17986.x
752:
14:
2402:
2361:Dipeptidyl peptidase-4 inhibitors
1137:
2338:
1421:
876:European Journal of Biochemistry
571:
565:
668:Key:SYOKIDBDQMKNDQ-XWTIBIIYSA-N
1092:
1043:
994:
969:
904:
789:
577:
559:
324:)-1-pyrrolidine-2-carbonitrile
1:
965:. Reuters. February 25, 2008.
782:
1984:Alpha-glucosidase inhibitors
699:, sold under the brand name
7:
2376:Drugs developed by Novartis
1946:Aldose reductase inhibitors
764:
10:
2407:
1812:GLP1 poly-agonist peptides
733:Combination with metformin
549:Chemical and physical data
2258:Sitagliptin/ertugliflozin
2253:Sitagliptin/dapagliflozin
2173:Glimepiride/rosiglitazone
2153:Empagliflozin/linagliptin
2143:Dapagliflozin/saxagliptin
2118:
2109:
2079:
2010:
1982:
1944:
1937:
1849:
1752:
1719:
1671:Glibenclamide (glyburide)
1616:
1604:
1595:
1564:
1531:
1468:
1440:
1431:
1427:
1416:
1354:
1317:
1274:
1256:
1228:
1224:
1207:
739:European Medicines Agency
676:
651:
631:
621:
599:
586:
553:
548:
529:
497:
477:
457:
437:
417:
397:
377:
352:
332:
308:
303:
291:
278:
260:
250:
240:
232:
194:
189:
149:
135:
117:
87:
69:
61:
51:
46:
37:
28:
2238:Pioglitazone/sitagliptin
2228:Pioglitazone/glimepiride
2218:Phenformin/sulfonylureas
2163:Gemigliptin/rosuvastatin
2133:Cagrilintide/semaglutide
727:type 2 diabetes mellitus
274:not appreciably involved
270:to inactive metabolite;
2268:Sitagliptin/simvastatin
2243:Rosiglitazone/metformin
2223:Pioglitazone/alogliptin
2213:Metformin/teneligliptin
2208:Metformin/sulfonylureas
2188:Metformin/ertugliflozin
2158:Empagliflozin/metformin
2138:Dapagliflozin/metformin
2128:Canagliflozin/metformin
1754:GLP-1 receptor agonists
1149:Drug Information Portal
2273:Vildagliptin/metformin
2233:Pioglitazone/metformin
845:10.1210/jc.2003-031907
776:Dipeptidyl peptidase-4
747:vildagliptin/metformin
57:Galvus, Zavamet others
2263:Sitagliptin/metformin
2248:Saxagliptin/metformin
2203:Metformin/repaglinide
2198:Metformin/gemigliptin
2178:Linagliptin/metformin
2193:Metformin/evogliptin
2123:Alogliptin/metformin
1118:10.1056/NEJMp1314078
1433:Insulin sensitizers
1188:diabetes medication
982:. www.ema.europa.eu
623:Solubility in water
213:(Prescription only)
81:UK Drug Information
25:
2312:Never to phase III
2183:Metformin/acarbose
1533:Dual PPAR agonists
1402:Never to phase III
1309:Ultralente insulin
930:10.2147/vhrm.s3005
705:anti-diabetic drug
21:
2391:Tertiary alcohols
2326:
2325:
2322:
2321:
2285:
2284:
2281:
2280:
2105:
2104:
1933:
1932:
1845:
1844:
1748:
1747:
1591:
1590:
1412:
1411:
1375:
1374:
1319:ultra-long-acting
1243:Insulin glulisine
1068:10.2337/db12-1686
1019:10.2337/db09-0058
694:
693:
612:Interactive image
499:CompTox Dashboard
221:
208:
100:
16:Chemical compound
2398:
2343:
2342:
2341:
2334:
2116:
2115:
2012:SGLT2 inhibitors
1942:
1941:
1851:DPP-4 inhibitors
1832:(GLP-1/GIP/GCGR)
1808:
1807:
1614:
1613:
1602:
1601:
1438:
1437:
1429:
1428:
1418:
1417:
1327:Insulin degludec
1289:Insulin glargine
1226:
1225:
1209:
1208:
1180:
1173:
1166:
1157:
1156:
1152:
1131:
1130:
1120:
1096:
1090:
1089:
1079:
1062:(7): 2595–2604.
1047:
1041:
1040:
1030:
1013:(7): 1604–1615.
998:
992:
991:
989:
987:
981:
973:
967:
966:
959:
953:
952:
942:
932:
923:(6): 1349–1360.
908:
902:
901:
891:
867:
858:
857:
847:
838:(5): 2078–2084.
823:
814:
813:
811:
809:
793:
690:
689:
682:
614:
594:
579:
573:
567:
561:
544:
533:
522:
521:
507:
505:
490:
470:
450:
430:
410:
390:
370:
360:
359:
345:
283:
219:
216:
206:
203:
177:
166:
110:
99:
96:
83:
42:
33:
26:
24:
20:
2406:
2405:
2401:
2400:
2399:
2397:
2396:
2395:
2351:
2350:
2349:
2339:
2337:
2329:
2327:
2318:
2317:
2302:Clinical trials
2277:
2101:
2075:
2006:
1978:
1929:
1841:
1806:
1744:
1715:
1609:
1587:
1560:
1527:
1472:/"glitazones" (
1464:
1423:
1408:
1407:
1392:Clinical trials
1371:
1350:
1331:+insulin aspart
1313:
1284:Insulin detemir
1270:
1266:Regular insulin
1252:
1220:
1218:insulin analogs
1203:
1196:insulin analogs
1184:
1143:
1140:
1135:
1134:
1097:
1093:
1048:
1044:
999:
995:
985:
983:
979:
975:
974:
970:
961:
960:
956:
909:
905:
868:
861:
824:
817:
807:
805:
794:
790:
785:
767:
755:
753:Adverse effects
735:
685:
683:
680:(what is this?)
677:
672:
669:
664:
659:
658:
647:
644:
639:
638:
617:
592:
582:
576:
570:
564:
525:
501:
493:
473:
453:
433:
413:
393:
373:
356:
348:
328:
325:
316:
315:
281:
252:Protein binding
242:Bioavailability
234:Pharmacokinetic
228:
185:
168:
138:
131:
128:Not recommended
120:
113:
17:
12:
11:
5:
2404:
2394:
2393:
2388:
2383:
2378:
2373:
2368:
2363:
2348:
2347:
2324:
2323:
2320:
2319:
2316:
2315:
2314:
2313:
2310:
2299:
2293:
2287:
2286:
2283:
2282:
2279:
2278:
2276:
2275:
2270:
2265:
2260:
2255:
2250:
2245:
2240:
2235:
2230:
2225:
2220:
2215:
2210:
2205:
2200:
2195:
2190:
2185:
2180:
2175:
2170:
2165:
2160:
2155:
2150:
2145:
2140:
2135:
2130:
2125:
2119:
2113:
2107:
2106:
2103:
2102:
2100:
2099:
2094:
2089:
2083:
2081:
2077:
2076:
2074:
2073:
2068:
2063:
2058:
2053:
2048:
2046:Luseogliflozin
2043:
2038:
2033:
2028:
2023:
2017:
2015:
2008:
2007:
2005:
2004:
1999:
1994:
1988:
1986:
1980:
1979:
1977:
1976:
1971:
1966:
1961:
1956:
1950:
1948:
1939:
1935:
1934:
1931:
1930:
1928:
1927:
1922:
1917:
1912:
1907:
1902:
1897:
1892:
1887:
1882:
1877:
1872:
1867:
1862:
1856:
1854:
1847:
1846:
1843:
1842:
1840:
1839:
1833:
1827:
1816:
1814:
1805:
1804:
1799:
1794:
1789:
1784:
1779:
1774:
1769:
1764:
1758:
1756:
1750:
1749:
1746:
1745:
1743:
1742:
1737:
1732:
1726:
1724:
1717:
1716:
1714:
1713:
1711:Glyclopyramide
1708:
1703:
1698:
1693:
1688:
1683:
1678:
1673:
1667:2nd generation
1663:
1662:
1657:
1652:
1647:
1642:
1640:Chlorpropamide
1637:
1632:
1626:1st generation
1622:
1620:
1611:
1607:
1599:
1593:
1592:
1589:
1588:
1586:
1585:
1580:
1574:
1572:
1562:
1561:
1559:
1558:
1553:
1548:
1543:
1537:
1535:
1529:
1528:
1526:
1525:
1520:
1515:
1510:
1505:
1500:
1495:
1490:
1485:
1479:
1477:
1466:
1465:
1463:
1462:
1457:
1452:
1446:
1444:
1435:
1425:
1424:
1414:
1413:
1410:
1409:
1406:
1405:
1404:
1403:
1400:
1389:
1383:
1377:
1376:
1373:
1372:
1370:
1369:
1366:
1362:
1360:
1352:
1351:
1349:
1348:
1341:Insulin icodec
1338:
1323:
1321:
1315:
1314:
1312:
1311:
1306:
1301:
1296:
1286:
1280:
1278:
1272:
1271:
1269:
1268:
1262:
1260:
1254:
1253:
1251:
1250:
1248:Insulin lispro
1245:
1240:
1238:Insulin aspart
1234:
1232:
1222:
1221:
1205:
1204:
1183:
1182:
1175:
1168:
1160:
1154:
1153:
1145:"Vildagliptin"
1139:
1138:External links
1136:
1133:
1132:
1111:(9): 794–797.
1091:
1042:
993:
968:
954:
903:
882:(3): 829–835.
859:
815:
804:on May 6, 2008
787:
786:
784:
781:
780:
779:
773:
766:
763:
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751:
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584:
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580:
574:
568:
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535:
527:
526:
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523:
515:DTXSID80881091
510:
508:
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492:
491:
483:
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463:
461:
455:
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155:
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147:
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133:
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125:
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115:
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111:
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15:
9:
6:
4:
3:
2:
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2300:
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2289:
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2108:
2098:
2095:
2093:
2092:Bromocriptine
2090:
2088:
2085:
2084:
2082:
2078:
2072:
2071:Velagliflozin
2069:
2067:
2066:Tofogliflozin
2064:
2062:
2061:Sotagliflozin
2059:
2057:
2054:
2052:
2051:Remogliflozin
2049:
2047:
2044:
2042:
2041:Ipragliflozin
2039:
2037:
2036:Ertugliflozin
2034:
2032:
2031:Empagliflozin
2029:
2027:
2026:Dapagliflozin
2024:
2022:
2021:Canagliflozin
2019:
2018:
2016:
2014:/"gliflozins"
2013:
2009:
2003:
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1915:Teneligliptin
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1618:Sulfonylureas
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1518:Rosiglitazone
1516:
1514:
1513:Rivoglitazone
1511:
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1504:
1503:Netoglitazone
1501:
1499:
1498:Lobeglitazone
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1304:Lente insulin
1302:
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1297:
1294:
1293:+lixisenatide
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532:ECHA InfoCard
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56:
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50:
47:Clinical data
45:
41:
36:
32:
27:
19:
2381:Carboxamides
2366:Pyrrolidines
2111:Combinations
2056:Sergliflozin
1925:Vildagliptin
1924:
1920:Trelagliptin
1900:Omarigliptin
1875:Garvagliptin
1802:Taspoglutide
1792:Orforglipron
1787:Lixisenatide
1721:Meglitinides
1676:Glibornuride
1666:
1650:Metahexamide
1645:Glycyclamide
1625:
1578:Cagrilintide
1568:analogs and
1556:Tesaglitazar
1551:Saroglitazar
1546:Muraglitazar
1523:Troglitazone
1508:Pioglitazone
1488:Darglitazone
1422:Non-insulins
1355:
1345:+semaglutide
1335:+liraglutide
1318:
1275:
1258:short-acting
1257:
1229:
1148:
1108:
1104:
1094:
1059:
1055:
1045:
1010:
1006:
996:
984:. Retrieved
971:
957:
920:
916:
906:
879:
875:
835:
831:
808:September 5,
806:. Retrieved
802:the original
791:
759:
756:
736:
724:
721:
700:
697:Vildagliptin
696:
695:
684:
678:
488:ChEMBL142703
321:
287:2 to 3 hours
280:Elimination
196:Legal status
190:Legal status
89:License data
23:Vildagliptin
18:
2386:Adamantanes
2298:from market
1910:Sitagliptin
1905:Saxagliptin
1895:Melogliptin
1890:Linagliptin
1885:Gosogliptin
1880:Gemigliptin
1853:/"gliptins"
1838:(GLP-1/GIP)
1836:Tirzepatide
1830:Retatrutide
1797:Semaglutide
1782:Liraglutide
1772:Dulaglutide
1767:Danuglipron
1762:Albiglutide
1740:Repaglinide
1735:Nateglinide
1730:Mitiglinide
1723:/"glinides"
1706:Glisoxepide
1691:Glimepiride
1681:Glicaramide
1660:Tolbutamide
1635:Carbutamide
1583:Pramlintide
1541:Aleglitazar
1493:Englitazone
1483:Ciglitazone
1388:from market
1299:NPH insulin
1276:long-acting
1230:fast-acting
595: g·mol
538:100.158.712
343:274901-16-5
304:Identifiers
62:Other names
53:Trade names
2355:Categories
2087:Benfluorex
1974:Zenarestat
1964:Ranirestat
1959:Fidarestat
1954:Epalrestat
1870:Evogliptin
1865:Anagliptin
1860:Alogliptin
1701:Gliquidone
1686:Gliclazide
1655:Tolazamide
1460:Phenformin
1442:Biguanides
783:References
600:3D model (
588:Molar mass
448:I6B4B2U96P
419:ChemSpider
379:IUPHAR/BPS
334:CAS Number
313:IUPAC name
268:hydrolysis
262:Metabolism
2308:Phase III
2296:Withdrawn
2097:Imeglimin
2002:Voglibose
1969:Tolrestat
1820:Mazdutide
1777:Exenatide
1696:Glipizide
1455:Metformin
1398:Phase III
1386:Withdrawn
1357:inhalable
743:metformin
707:) of the
293:Excretion
282:half-life
180:metformin
137:Routes of
119:Pregnancy
75:Drugs.com
2371:Nitriles
2345:Medicine
1997:Miglitol
1992:Acarbose
1450:Buformin
1214:Insulins
1192:insulins
1127:24571751
1086:23524641
1056:Diabetes
1037:19403868
1007:Diabetes
986:July 29,
977:"Galvus"
949:19337548
854:15126524
765:See also
687:(verify)
399:DrugBank
178:) (with
151:ATC code
144:By mouth
121:category
1822:(GLP-1/
1368:Afrezza
1365:Exubera
1077:3712065
1028:2699878
940:2663430
898:8100523
593:303.406
555:Formula
428:5293734
408:DB04876
368:6918537
354:PubChem
266:Mainly
172: (
170:A10BD08
167:)
161: (
159:A10BH02
105::
2331:Portal
2291:WHO-EM
1570:DACRAs
1566:Amylin
1381:WHO-EM
1125:
1084:
1074:
1035:
1025:
947:
937:
896:
852:
778:(CD26)
701:Galvus
636:SMILES
479:ChEMBL
468:D07080
298:Kidney
272:CYP450
209:
108:by INN
101:
65:LAF237
2080:Other
1938:Other
1186:Oral
980:(PDF)
713:GLP-1
656:InChI
602:JSmol
1824:GCGR
1474:PPAR
1470:TZDs
1194:and
1123:PMID
1082:PMID
1033:PMID
988:2018
945:PMID
894:PMID
850:PMID
810:2008
737:The
715:and
459:KEGG
439:UNII
388:6310
256:9.3%
236:data
71:AHFS
1608:ATP
1200:A10
1113:doi
1109:370
1072:PMC
1064:doi
1023:PMC
1015:doi
935:PMC
925:doi
884:doi
880:214
840:doi
717:GIP
504:EPA
358:CID
246:85%
211:POM
175:WHO
164:WHO
103:EMA
2357::
2304::
1669::
1628::
1394::
1333:,
1190:,
1147:.
1121:.
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1060:62
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1031:.
1021:.
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818:^
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563:17
218:EU
205:UK
98:EU
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220::
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182:)
73:/
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
