Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects.
OBJECTIVE
To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels.


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 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees 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.
Mannucci
E
E
Department of Clinical Pathophysiology, University of Florence, Italy.
Ognibene
A
A
Cremasco
F
F
Bardini
G
G
Mencucci
A
A
Pierazzuoli
E
E
Ciani
S
S
Messeri
G
G
Rotella
C M
CM
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D020738:Leptin / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D020738:Leptin; D010446:Peptide Fragments; D010455:Peptides; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D008687:Metformin; C051322:glucagon-like peptide 1 (7-37)