Effect of DPP-4 inhibitor on insulin secretion and insulin sensitivity

Not Applicable

• Conditions: Type 2 diabetes mellitus

• Registration Number: JPRN-UMIN000005283
• Lead Sponsor: Study group of incretin in Saitama

Brief Summary

We compared directly these sitagliptin (SIT) and mitiglinide (MIT) in 16 type 2 diabetic patients (M/F=10/6, Age: 66+/-3 y.o., BMI: 24+/-4kg/m2, HbA1c: 6.6+/-0.5%, FPG: 116+/-27mg/dl). Patients received SIT (50mg qd for 1 week and 100mg qd for an additional week) or MIT (10mg tid for 2 weeks). After 2 weeks, patients crossed-over to an alternative treatment. 75 g oral glucose tolerance tests (OGTT) were conducted before the study and after interventions. The average of area under the curve (aAUC) up to 180 min of PG response was similar in both agents and lower than before (CON) (SIT 179+/-53, MIT 174+/-50 vs CON 222+/-60 mg/dl, p<0.0001). Insulinogenic index was highest in MIT (0.3+/-0.3 vs SIT 0.2+/-0.2, p<0.01; vs CON 0.1+/-0.1, p<0.01), while the Matsuda index was similar in 3 OGTTs (MIT 10+/-5, SIT 11+/-7, CON 11+/-7). aAUC of GLP-1 was increased in SIT (15+/-14 vs MIT 6+/-5, p<0.001; vs CON 5+/-4 pmol/L, p<0.001). The incremental aAUC of glucagon was lower in SIT (-2.4+/-12.9 vs MIT 6.2+/-14.0, p<0.05; vs CON -0.7+/-15.0 ng/ml), although basal glucagon levels were paradoxically higher in SIT (77+/-17, vs MIT 71+/-18 p<0.05; vs CON 74+/-20 ng/ml). aAUC of proinsulin was decreased in SIT (15.0+/-3 8, vs MIT 21.4+/-9.8, p<0.01; vs CON 17.2+/-8.6 pmol/L, p<0.05). Triglyceride levels were reduced by MIT. There were no differences between subjects who randomly started with SIT first and those with MIT first. While clinical doses of SIT and MIT resulted in a similar PG control, SIT enhanced less insulin secretion with less glucagon responses and much less proinsulin responses compared with MIT. Thus these changes of hormonal profiles by SIT favor islet functions compared with MIT in clinical use.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-03-22
• Study Completion: 2011-12-01
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: Complete: follow-up complete
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

1) Under the treatment with insulin 2) Type 1 diabetic subjects or diabetic subjects who have HbA1c (NSGP) more than or equal to 9.4 % or who need admission because of diabetic ketoacidosis or extreme hyperglycemia. 3) Subjects with alpha glucosidase inhibitors. 4) Subjects who are treated with sulfonylureas (i.e. glibenclamide, glimepiride, or gliclazide). 5) Subjects with nephrotic syndrome (urine protein more than or equal to 3.5g/day and serum protein less than or equal to 6.0 g/dl [or serum albumin less than or equal to 3.0 g/dl]. 6) Subjects who are taking steroids, immune suppression medication, antifungal medication of azoles. HIV protease inhibitors 7) Subjects with previous serious adverse events (possible and prolonged situations to influence usual daily activity or to add hospital admission duration) with DPP-4 inhibitors and glinides. 8) Subjects who had brain stroke or acute coronary syndrome within 6 months before enrollment. 9) Subjects with severe heart failure (NYHA class 3 or higher), severe arrhythmia (frequent atrial or ventral arrhythmia, continuous ventricular tachycardia, severe atrial tachycardia, atrial fibrillation or flutter with severe tachycardia, sick sinus syndrome or atrial-ventral block with severe bradycardia). 10) Subjects who have AST or ALT more than 5 times of upper normal limit of their institute 11) Subjects with malignancy 12) Subjects who are pregnant or who have intention to be pregnant 13) Subjects with other situations under which a doctor in charge decides that subjects are not eligible for this study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
AUC (area under the curve) of glucagon response during OGTT between sitagliptin treatment and miglitol treatment

Secondary Outcome Measures

Name	Time	Method
Markers of insulin secretion and insulin sensitivity and relation between those markers and effect of medication on glycoalbumin, fasting plasma glucose, and 2hr plasma glucose.