Berhane Seyoum, Alemu Fite and Abdul Abou-Samra
Ghrelin is an appetite-stimulating hormone mainly produced by the stomach. Circulating levels of ghrelin increase in fasting sates and fall following meal. Sitagliptin is an orally available new class of anti-diabetic drug that inhibits dipeptidyl peptidase-4 (DPP-4) leading to 2-3 fold increase in the serum concentration of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This study was performed to determine the effects of sitagliptin on circulating levels of ghrelin in control subjects (N=15) and diabetic patients (N=46). The diabetic patients were treated with sitagliptin (N=15), metformin (N=16) or combination of sitagliptin and metformin (N=15) for one week. Serum concentrations of total and active ghrelin were determined immediately before and 2 hours after meal challenge. The tests were repeated among patients with diabetes after receiving drug therapy for one week. Active ghrelin was significantly more suppressed than total ghrelin in diabetic patients (by 36%, p<0.001). In patients taking sitagliptin, total ghrelin (means±SEM) fell from 386±37 pg/ml at baseline to 345±73 pg/ml whereas active ghrelin decreased from 160±18 pg/ml to 85±12 pg/ml (p<0.01). There was no statistical difference in ghrelin levels between the three treatment groups. Active ghrelin concentration correlated negatively with BMI in diabetic patients (P<0.05). After adjusting data for sitagliptin or its combination with metformin suppressed active: total ghrelin ratio more potently than metformin alone (P<0.001). Sitagliptin suppressed active ghrelin more significantly in patients with diabetes when compared to healthy controls. Postprandial ghrelin suppression was strongest after medication. The result of this study warrants further investigation of the significance of ghrelin suppression in patients with diabetes.