Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects
- Edoardo Mannucci, MD1,
- Agostino Ognibene, MD2,
- Francesco Cremasco, MD1,
- Gianluca Bardini, MD1,
- Antonella Mencucci, MD1,
- Enrica Pierazzuoli, MD1,
- Silvia Ciani, BS1,
- Gianni Messeri, MS2 and
- Carlo M. Rotella, MD1
- 1Section of Endocrinology, Department of Clinical Pathophysiology, University of Florence
- 2Clinical Chemistry Laboratory, Careggi General Hospital, Florence, Italy
Abstract
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.
- ANOVA, analysis of variance
- CV, coefficient of variation
- DPP-IV, dipeptidyl peptidase IV
- GLP-1, glucagon-like peptide 1
Footnotes
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Address correspondence and reprint requests to Prof. Carlo M. Rotella, Insegnamento di Malattie Metaboliche e del Ricambio, Dipartimento di Fisiopatologia Clinica, Viale Pieraccini, 6-50134 Firenze, Italy. E-mail: c.rotella{at}dfc.unifi.it.
Received for publication 13 July 2000 and accepted in revised form 10 November 2000.
C.M.R. is a member of the International Advisory Board on GLP-1 analogs of Novo Nordisk, Denmark. He has received honoraria from Molteni Farmaceutici, Firenze, and Bayer Farmaceutici, Milan, Italy, which are currently marketing metformin in Italy. E.M. is a paid consultant for Molteni Farmaceutici.
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