Unveiling the Differential Impact of Clarithromycin and Metronidazole on the Incretin Effect of Sitagliptin

Résumé

Background: Sitagliptin is a commonly used drug for the treatment of type 2 diabetes. Studies show that diabetic patients are at high risk of suffering severe complications after amoebic infection. To treat these amoebic infections drugs like clarithromycin and metronidazole are most commonly indicated. Methods: Studies were conducted in normal male Wistar rats with oral doses of 10 mg/kg body weight of sitagliptin, 10 mg/kg body weight of clarithromycin & 5 mg/kg body weight of metronidazole, and their combination for duration of 14 days. Blood glucose level was analyzed on weekly basis with the help of a glucometer. For measuring plasma insulin the blood was collected with heart puncture and analyzed with the help of ELISA. Result: The clarithromycin and metronidazole themselves do not have any hypoglycemic.However, when clarithromycin is used together with sitagliptin, it increases the anti-diabetic effect of sitagliptin. This means that there is drug-drug interaction between clarithromycin and sitagliptin. After evaluation of liver drug-metabolizing enzyme, it was concluded that clarithromycin inhibits the CYP3A4 enzyme which is responsible for the metabolism of sitagliptin. As a result the anti-diabetic effect of sitagliptin increases. However, together use of metronidazole and sitagliptin do not have such type of drug interactions. Conclusion: From this study it was concluded that the combined use of clarithromycin and sitagliptin may need a little dose adjustment and care should be taken when the combination is prescribed to the patient. While the combination use of metronidazole with sitagliptin has no significant effect on sitagliptin therapy.