Additive effects of glucagon-like peptide 1 and pioglitazone in patients with type 2 diabetes.
OBJECTIVE
To evaluate the effect of combination therapy with pioglitazone and glucagon-like peptide (GLP)-1 in patients with type 2 diabetes.


METHODS
Eight patients with type 2 diabetes (BMI 32.7 +/- 1.3 kg/m(2) and fasting plasma glucose 13.5 +/- 1.2 mmol/l) underwent four different treatment regimens in random order: saline therapy, monotherapy with continuous subcutaneous infusion of GLP-1 (4.8 pmol x kg(-1) x min(-1)), monotherapy with pioglitazone (30-mg tablet of Actos), and combination therapy with GLP-1 and pioglitazone. The observation period was 48 h. End points were plasma levels of glucose, insulin, glucagon, free fatty acids (FFAs), and sensation of appetite.


RESULTS
Fasting plasma glucose decreased from 13.5 +/- 1.2 mmol/l (saline) to 11.7 +/- 1.2 (GLP-1) and 11.5 +/- 1.2 (pioglitazone) and further decreased to 9.9 +/- 1.0 (combination) (P < 0.001). Eight-hour mean plasma glucose levels were reduced from 13.7 +/- 1.1 mmol/l (saline) to 10.6 +/- 1.0 (GLP-1) and 12.0 +/- 1.2 (pioglitazone) and were further reduced to 9.5 +/- 0.8 (combination) (P < 0.0001). Insulin levels increased during monotherapy with GLP-1 compared with monotherapy with pioglitazone (P < 0.01). Glucagon levels were reduced in GLP-1 and combination therapy compared with saline and monotherapy with pioglitazone (P < 0.01). FFAs during breakfast (area under the curve, 0-3 h) were reduced in combination therapy compared with saline (P = 0.03). Sensation of appetite was reduced during monotherapy with GLP-1 and combination therapy (P < 0.05).


CONCLUSIONS
GLP-1 and pioglitazone show an additive glucose-lowering effect. A combination of the two agents may, therefore, be a valuable therapeutic approach for the treatment of type 2 diabetes.
Department of Endocrinology, Hvidovre Hospital, Kettegaards Allé 30, 2650 Hvidovre, Denmark. m.zander@dadlnet.dk
Mette
M
Zander
Allan
A
Christiansen
Sten
S
Madsbad
Jens Juul
JJ
Holst
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000097:blood / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D000077205:Pioglitazone; D011498:Protein Precursors / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*
D001786:Blood Glucose; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D000077205:Pioglitazone; D011498:Protein Precursors; D045162:Thiazolidinediones