title: Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with Type 2 diabetes mellitus.
abstract: OBJECTIVE
  Studies investigating the acute effects of metformin have demonstrated actions on the incretin system and appetite regulatory hormones. There are limited data to support that these effects are sustained in the long term. We therefore studied the effects of chronic treatment with metformin on endogenous glucagon-like peptide 1, dipeptidyl peptidase-4 activity and active ghrelin (an orexigenic hormone) in obese patients with Type 2 diabetes mellitus.
  
  
  METHODS
  Eight subjects [six male, age 58.7 ± 2.6 years, BMI 41.1 ± 2.9 kg/m(2) , HbA(1c) 69 ± 6 mmol/mol (8.5 ± 0.5%), mean ± sem] with drug-naïve Type 2 diabetes were studied for 6 h following a standard mixed meal, before and after at least 3 months of metformin monotherapy (mean dose 1.75 g daily).
  
  
  RESULTS
  The area under the curve (AUC(0-6 h) ) for active glucagon-like peptide 1 was significantly higher on metformin (pre-metformin 1750.8 ± 640 pmol l(-1) min(-1) vs. post-metformin 2718.8 ± 1182.3 pmol l(-1) min(-1) ; P=0.01). The areas under the curves for dipeptidyl peptidase-4 activity and ghrelin were not significantly different pre- and post-treatment with metformin.
  
  
  CONCLUSIONS
  Three months or more of metformin monotherapy in obese patients with Type 2 diabetes was associated with increased postprandial active glucagon-like peptide 1 levels. The effects of metformin on the enteroinsular axis may represent yet another important mechanism underlying its glucose-lowering effects.
authors.affiliation: Diabetes and Endocrinology Clinical Research Group, University Hospital Aintree, Clinical Sciences Centre, Liverpool, UK. s.thondam@liverpool.ac.uk
authors.forename: S K
authors.initials: SK
authors.lastname: Thondam
authors.forename: A
authors.initials: A
authors.lastname: Cross
authors.forename: D J
authors.initials: DJ
authors.lastname: Cuthbertson
authors.forename: J P
authors.initials: JP
authors.lastname: Wilding
authors.forename: C
authors.initials: C
authors.lastname: Daousi
mesh_terms: D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D054439:Ghrelin / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D019518:Postprandial Period; D011446:Prospective Studies
chemical_list: D054439:Ghrelin; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D018819:Dipeptidyl Peptidase 4