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.

Abstract

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 PYY(3- 36), and increased PYY(1- 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.

• Authors: K Aaboe, F K Knop, T Vilsbøll, C F Deacon, J J Holst, S Madsbad, T Krarup
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 12 Issue 4 Pg. 323-33 (Apr 2010) ISSN: 1463-1326 [Electronic] England
• PMID: 20380653 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Glucagon-Like Peptide 2
• Hypoglycemic Agents
• Insulin
• Pyrazines
• Triazoles
• Peptide YY
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Metformin
• Sitagliptin Phosphate

Topics

• Adult
• Aged
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (administration & dosage, therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Gastric Inhibitory Polypeptide (blood)
• Glucagon-Like Peptide 1 (blood)
• Glucagon-Like Peptide 2 (blood)
• Humans
• Hypoglycemic Agents (administration & dosage, therapeutic use)
• Insulin (metabolism)
• Insulin Secretion
• Male
• Metformin (administration & dosage, therapeutic use)
• Middle Aged
• Peptide YY (metabolism)
• Postprandial Period
• Pyrazines (administration & dosage, therapeutic use)
• Sitagliptin Phosphate
• Triazoles (administration & dosage, therapeutic use)