Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes.
OBJECTIVE
The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients.


METHODS
In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite.


RESULTS
Fasting plasma glucose (day 2) decreased from 13.9 +/- 1 (no treatment) to 11.2 +/- 0.4 (metformin) and 11.5 +/- 0.5 (GLP-1) and further decreased to 9.4 +/- 0.7 (combination therapy) (P = 0.0005, no difference between monotherapy with GLP-1 and metformin). The 24-h mean plasma glucose (day 2) decreased from 11.8 +/- 0.5 (metformin) and 11.7 +/- 0.8 (GLP-1) to 9.8 +/- 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect on appetite scores.


CONCLUSIONS
Monotherapy with GLP-1 and metformin have equal effects on plasma glucose and additive effects upon combination.
Zander
M
M
Department of Endocrinology, Hvidovre Hospital, Denmark.
Taskiran
M
M
Toft-Nielsen
M B
MB
Madsbad
S
S
Holst
J J
JJ
D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005768:Gastrointestinal Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D012107:Research Design
D001786:Blood Glucose; D002096:C-Peptide; D005768:Gastrointestinal Hormones; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007328:Insulin; D008687:Metformin; D010446:Peptide Fragments; D010919:Placebos; C055453:glucagon-like peptide 1 (7-36)amide