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Diabetes Care 27:1910-1914, 2004
© 2004 by the American Diabetes Association, Inc.

Emerging Treatments and Technologies
Original Article

Additive Effects of Glucagon-Like Peptide 1 and Pioglitazone in Patients With Type 2 Diabetes

Mette Zander, MD, PHD1,2, Allan Christiansen, MD1,2, Sten Madsbad, MD, DMSC1 and Jens Juul Holst, MD, DMSC2

1 Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
2 Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark

Address correspondence and reprint requests to Mette Zander, Department of Endocrinology, Hvidovre Hospital, Kettegaards Allé 30, 2650 Hvidovre, Denmark. E-mail: m.zander{at}dadlnet.dk

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

RESEARCH DESIGN AND METHODS—Eight patients with type 2 diabetes (BMI 32.7 ± 1.3 kg/m2 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 · kg–1 · 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.

Abbreviations: AUC, area under the curve • FFA, free fatty acid • GLP, glucagon-like peptide


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Copyright © 2004 by the American Diabetes Association.