Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability?

Aim: Effects of metformin and pioglitazone on body weight are clearly different. Recently, the role of ghrelin, an orexigenic peptide derived from stomach, has been appreciated. Plasma ghrelin levels display a preprandial peak and postprandial suppression, suggesting its physiological role. We hypothesized that metformin or pioglitazone may modulate circulating ghrelin levels and this modulation may be related to differential effects on body weight with these agents. Methods: Thirty-five Japanese type 2 diabetic patients [ 21 men and 14 women, age 62 +/- 2 years, body mass index (BMI) 26.6 +/- 0.5 kg/m(2) and haemoglobin A1c (HbA1c) 8.2 +/- 0.1%, mean +/- s.e.] were randomly assigned to groups for the addition of metformin or pioglitazone. At baseline and 4 months later, a 75-g oral glucose tolerance test (OGTT) was performed to measure plasma ghrelin levels. Results: In 33 subjects who completed the study, the overall decrease in HbA1c (similar to 1%) was comparable between the two groups. As expected, BMI increased in the pioglitazone group but not in the metformin group. After the treatment, plasma ghrelin levels at each point of OGTT remained unchanged in the pioglitazone group. In the metformin group, fasting ghrelin levels were unaltered, whereas the absolute levels at 30, 60 and 120 min decreased significantly. The area under the curve for the 2-h ghrelin profile also decreased significantly. Conclusions: Metformin, but not pioglitazone, decreased plasma ghrelin levels after the glucose load. This decrease may in part account for weight stability in type 2 diabetic patients treated with metformin.