Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus
Article first published online: 6 NOV 2009
© 2010 Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism
Volume 12, Issue 4, pages 323–333, April 2010
How to Cite
Aaboe, K., Knop, F. K., Vilsbøll, T., Deacon, C. F., Holst, J. J., Madsbad, S. and Krarup, T. (2010), Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus. Diabetes, Obesity and Metabolism, 12: 323–333. doi: 10.1111/j.1463-1326.2009.01167.x
- Issue published online: 25 FEB 2010
- Article first published online: 6 NOV 2009
- Date submitted 8 September 2009; date of final acceptance 16 October 2009
- DPP-4 inhibition;
- glucagon-like peptide-1;
- glucagon-like peptide 2;
- glucose-dependent insulinotropic polypeptide;
- incretin effect;
- insulin secretion;
- peptide YY;
- type 2 diabetes mellitus
Aim: To examine the effects of 12 weeks of treatment with the DPP-4 inhibitor, sitagliptin, on gastrointestinal hormone responses to a standardized mixed meal and beta cell secretory capacity, measured as glucose and non-glucose induced insulin secretion during a hyperglycaemic clamp, in patients with type 2 diabetes.
Method: A double-blinded, placebo-controlled study over 12 weeks in which 24 patients with T2DM were randomized to receive either sitagliptin (Januvia) 100 mg qd or placebo as an add-on therapy to metformin. In week 0, 1 and 12 patients underwent a meal test and a 90-min 20 mM hyperglycaemic clamp with 5 g of l-arginine infusion. Main outcome measure was postprandial total glucagon-like peptide 1 (GLP-1) concentration. Additional measures were insulin and C-peptide, glycaemic control, intact and total peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP), and intact glucagon-like peptide 2 (GLP-2) and GLP-1.
Results: All patients [sitagliptin n = 12, age: 59.5 (39–64) years, HbA1c: 8.0 (7.3–10.0)%, BMI: 33.2 (29.3–39.4); placebo n = 12, age: 60 (31–72) years, HbA1c: 7.7 (7.1–9.8)%, BMI: 30.7 (25.7–40.5)] [median (range)] completed the trial. Sitagliptin treatment improved glycaemic control, had no effect on total GLP-1, GIP or intact GLP-2, but reduced total PYY and PYY3- 36, and increased PYY1- 36 and intact incretin hormones. Sitagliptin improved first and second phases of beta cell secretion and maximal secretory capacity. All effects were achieved after 1 week. No significant changes occurred in the placebo group.
Conclusion: The postprandial responses of total GLP-1 and GIP and intact GLP-2 were unaltered. PYY degradation was prevented. Glucose and non-glucose induced beta cell secretion was improved. There was no difference in responses to sitagliptin between 1 and 12 weeks of treatment.