Cited by 300Diabetes Treatment and ManagementRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects

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Mannucci, Edoardo, Ognibene, Agostino, Cremasco, Francesco, Bardini, Gianluca, Mencucci, Antonella, Pierazzuoli, Enrica, Ciani, Silvia, Messeri, Gianni +1 more·2001·Diabetes Care

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.

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Crossref · 10.2337/diacare.24.3.489

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  • Metformin increases plasma GLP-1 levels, probably by either direct inhibition of DPPIV or by increased secretion, leading to reduced food intake and weight loss.

    “Metformin has also been found to increase plasma GLP-1 levels, probably by either direct inhibition of DPPIV or by increased secretion, leading to reduced food intake and weight loss [40].”
  • Metformin may contribute to weight loss by inducing a lipolytic and anorectic effect through action on glucagon-like peptide 1.

    “and by induction of a lipolitic and anoretic effect by acting on glucagon–like peptide 1 [40].”

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Authors
Mannucci, E., Ognibene, A., Cremasco, F., Bardini, G., Mencucci, A., Pierazzuoli, E., Ciani, S., Messeri, G., & Rotella, C. M.
Affiliations
  • University of Florence (IT)
  • Azienda Ospedaliero-Universitaria Careggi (IT)
Corresponding author
Rotella, Carlo M.
Venue
Diabetes Care
Published
2001-03-01
Volume
24
Issue
3
Pages
489-494
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
OpenAlex
W2157841460
Cited by
300
References
26
Citations by year
2026: 5 · 2025: 6 · 2024: 11 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 6 · 2019: 11 · 2018: 17 · 2017: 20 · 2016: 24 · 2015: 12 · 2014: 14 · 2013: 26 · 2012: 18
FWCI
3.46
Type
journal article
Language
en
Licence
other-oa
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
metformin, glucagon-like peptide-1, leptin, obesity, GLP-1(7-36)amide, dipeptidyl peptidase IV, oral glucose load, hyperinsulinemic-euglycemic clamp, incretin secretion
MeSH terms
Adolescent, Adult, Blood Glucose, Glucagon-Like Peptides, Glucagon, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Obesity, Peptide Fragments, Peptides, Glucose Clamp Technique, Leptin, Glucagon-Like Peptide 1

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