Exenatide treatment causes suppression of serum fasting ghrelin levels in patients with type 2 diabetes mellitus

Abstract

Aim: In the present study, we investigated the long-term effects of exenatide treatment on serum fasting ghrelin levels in patients with type 2 diabetes mellitus. Methods: Type 2 diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose for at least 3 months, were enrolled in the study. BMI>35 kg/m(2) and HbA1c>7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were stopped, and metformin treatment was continued at 2000 mg per day. Exenatide treatment was initiated at 5 mu g per dose subcutaneously (sc) twice daily, and after one month, the dose of exenatide was increased to 10 mu g twice daily. Changes in anthropometric variables, glycemic control, lipid parameters and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. Results: Thirty-eight patients (male/female = 7/31) entered the study. The mean age of patients was 50.5 +/- 8.8 years with a mean diabetes duration of 8.5 +/- 4.9 years. The mean BMI was 41.6 +/- 6.3 kg/m(2) and the mean HbA1c of patients was 8.9 +/- 1.4%. The mean change in the weight of patients was -5.6 kg and the percentage change in weight was -5.2 +/- 3.7% following 12 weeks of treatment. BMI, fasting plasma glucose and HbA1c levels of patients were decreased significantly (P < 0.001 and P < 0.001; respectively), while there was no change in lipid parameters. Serum fasting ghrelin levels were significantly suppressed following 12 weeks of exenatide treatment compared with baseline values (328.4 +/- 166.8 vs 245.3 +/- 164.8 pg/mL) (P = 0.024). Conclusion: These results suggest that the effects of exenatide on weight loss may be related with the suppression of serum fasting ghrelin levels, which is an orexigenic peptide.