TY - JOUR
T1 - 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
AU - Aaboe, K
AU - Knop, F K
AU - Vilsbøll, T
AU - Deacon, C F
AU - Holst, Jens Juul
AU - Madsbad, S
AU - Krarup, Troels Magelund
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Diabetes Mellitus, Type 2
KW - Dipeptidyl-Peptidase IV Inhibitors
KW - Double-Blind Method
KW - Drug Administration Schedule
KW - Female
KW - Gastric Inhibitory Polypeptide
KW - Glucagon-Like Peptide 1
KW - Glucagon-Like Peptide 2
KW - Humans
KW - Hypoglycemic Agents
KW - Insulin
KW - Male
KW - Metformin
KW - Middle Aged
KW - Peptide YY
KW - Postprandial Period
KW - Pyrazines
KW - Triazoles
U2 - 10.1111/j.1463-1326.2009.01167.x
DO - 10.1111/j.1463-1326.2009.01167.x
M3 - Journal article
C2 - 20380653
SN - 1462-8902
VL - 12
SP - 323
EP - 333
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 4
ER -
