INCRETIN HORMONES, NAMELY GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AND GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE (GIP), ARE RELEASED FROM ENTEROENDOCRINE CELLS AND ENHANCE INSULIN SECRETION. INCRETINS ARE RAPIDLY INACTIVATED BY THE ENZYME DIPEPTIDYL PEPTIDASE-4 (DPP-4), AND HAVE A VERY SHORT HALF-LIFE (T1/2) AS A RESULT. DPP-4 INHIBITORS INCREASE THE LEVELS OF ACTIVE GLP-1 AND GIP BY INHIBITING DPP-4 ENZYMATIC ACTIVITY; THUS, IN PATIENTS WITH DIABETES, THESE INHIBITORS IMPROVE HYPERGLYCEMIA IN A GLUCOSE-DEPENDENT MANNER BY INCREASING SERUM INSULIN LEVELS AND DECREASING SERUM GLUCAGON LEVELS. THEREFORE, INCRETIN-RELATED AGENTS SUCH AS DPP-4 INHIBITORS ARE PROMISING DRUGS THAT CAN DECREASE GLUCOSE FLUCTUATIONS IN DIABETIC PATIENTS AND HAVE EMERGED AS A NEW CLASS OF ANTIDIABETIC.
TENELIGLIPTIN IS A NOVEL CHEMOTYPE PROLYLTHIAZOLIDINE-BASED DPP-4 INHIBITOR.
POSTPRANDIAL GLUCAGON LEVELS ARE SIGNIFICANTLY DECREASED AFTER BREAKFAST AND LUNCH AS WELL AS AFTER DINNER IN THE 20 MG TENELIGLIPTIN & THE POSTPRANDIAL INSULIN LEVELS SIGNIFICANTLY INCREASED.
THE MAXIMUM PERCENTAGE OF THE INHIBITION IN PLASMA DPP-4 ACTIVITY WAS ACHIEVED WITHIN 2 HOURS AFTER ADMINISTRATION. THE ACTIVE GLP-1 CONCENTRATION IN THE PLASMA IN THE 10 MG AND 20 MG TENELIGLIPTIN GROUPS WAS HIGHER THAN THAT IN THE PLACEBO GROUP THROUGHOUT THE DAY, EVEN AT 24 HOURS AFTER ADMINISTRATION.
IT REDUCED THE LEVELS OF POSTPRANDIAL TRIGLYCERIDES AND FREE FATTY ACIDS AND ALSO INCREASED THE LEVELS OF GLP-1 AND INSULIN. GLP-1 INHIBITS THE SECRETION OF GASTRIC LIPASE AND REDUCES INTESTINAL TRIGLYCERIDE ABSORPTION AND APO B AND APO A-IV PRODUCTION AND INSULIN SUPPRESSES LIPOLYSIS IN ADIPOSE TISSUE, RESULTING IN A REDUCTION OF THE PLASMA FREE FATTY ACID LEVELS.