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.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Aaboe
K
K
Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Denmark.
Knop
F K
FK
Vilsbøll
T
T
Deacon
C F
CF
Holst
J J
JJ
Madsbad
S
S
Krarup
T
T
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D053767:Glucagon-Like Peptide 2 / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D019894:Peptide YY / Q000378:metabolism*; D019518:Postprandial Period; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D054873:Dipeptidyl-Peptidase IV Inhibitors; D053767:Glucagon-Like Peptide 2; D007004:Hypoglycemic Agents; D007328:Insulin; D011719:Pyrazines; D014230:Triazoles; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D000068900:Sitagliptin Phosphate