PT  - JOURNAL ARTICLE
AU  - Mannucci, Edoardo
AU  - Ognibene, Agostino
AU  - Cremasco, Francesco
AU  - Bardini, Gianluca
AU  - Mencucci, Antonella
AU  - Pierazzuoli, Enrica
AU  - Ciani, Silvia
AU  - Messeri, Gianni
AU  - Rotella, Carlo M.
TI  - Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects
AID  - 10.2337/diacare.24.3.489
DP  - 2001 Mar 01
TA  - Diabetes Care
PG  - 489--494
VI  - 24
IP  - 3
4099  - http://care.diabetesjournals.org/content/24/3/489.short
4100  - http://care.diabetesjournals.org/content/24/3/489.full
SO  - Diabetes Care2001 Mar 01; 24
AB  - OBJECTIVE—To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS—A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7–36)amide/(7–37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7–36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS—Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7–36)amide/(7–37) at 30 and 60 min after the oral glucose load (63.8 ± 29.0 vs. 50.3 ± 15.6 pmol/l and 75.8 ± 35.4 vs. 46.9 ± 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1–0.5 μg/ml) significantly inhibited degradation of GLP-1(7–36)amide after a 30-min incubation at 37°C; similar results were obtained in a buffer solution containing DPP-IV. CONCLUSIONS—Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.