Sitagliptin (DPP-4 Inhibitor) and NPH Insulin in Patients With T2D

Study Overview
=================
Brief Summary
-----------------
To compare the short and long term effects of inhibitor of the DPP-IV enzyme, sitagliptin , with bedtime NPH insulin in patients with T2D inadequately controlled with sulphonylurea plus biguanide: effects on beta cell function and on metabolic profile.

Detailed Description
-----------------
Glucose control is fundamental in the treatment of type 2 diabetes (DM2). Studies suggest that drugs that boost levels of glucagon-like peptide (GLP-1) improve glycemic control and have long-term beneficial effect on the function of pancreatic beta cells. Objective: To compare the short and long term effects of sitagliptin (which inhibits the DPP-IV enzyme, increasing the levels of GLP-1) with bedtime NPH insulin in patients with T2D inadequately controlled with sulphonylurea plus biguanide. Effects on beta cell function and on metabolic profile were analyzed. Methods: 40 patients with DM2, HbA1c between 6.6 to 10%, in use of metformin and glibenclamide will be randomized to the addition of sitagliptin (Sitagliptin Group) or of bedtime NPH insulin (NPH Group). Measurements of HbA1c, metabolic and hormonal profile at fasting and post-meal (every 30 minutes for 4 hours) will be evaluated before and after 6 months (short term) and 12 months (long term) of adding sitagliptin or NPH insulin.

Official Title
-----------------
Short and Long Term Effects of a Dypeptidil-peptidase-4 Versus Bedtime NPH Insulin as add-on Therapy in Patients With Type 2 Diabetes

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: sitagliptin
* Drug: NPH insulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria outpatients with T2D inadequately controlled with metformin plus glyburide HbA1c levels between 6.6 and 10% body mass index < 35 kg/m2 Exclusion Criteria heart failure respiratory failure uncontrolled hypertension impaired hepatic function impaired reanl function endocrine disorder gastrointestinal disorder malignancy alcohol abuse previous use of insulin previou use of based incretin therapy type 1 diabetes.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sitagliptin<br>100mg every day of sitagliptin in patients that were previosly using metformin and glyburide | Drug: sitagliptin<br>* patients with type 2 diabetes,inadequately controlled with metformin plus glyburide, HbA1c between 6.6 to 10%, will be randomized to the addition of sitagliptin (Sitagliptin Group) or of bedtime NPH insulin (NPH Group) during one year<br>* Other names: DPP-4 inhibitor;|
| Active Comparator: NPH insulin<br>NPH insulin will be applied bedtime every night in patients that awere previously using metformin and glyburide,The insulin dosage will be adjusted to fasting glycemia between 90 and 100 mg / dL | Drug: NPH insulin<br>* patients with type 2 diabetes,inadequately controlled with metformin plus glyburide, HbA1c between 6.6 to 10%, will be randomized to the addition of sitagliptin (Sitagliptin Group) or of bedtime NPH insulin (NPH Group) during one year<br>* Other names: long-acting insulin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement in HbA1c levels | Changes in fasting blood levels of HBA1c (%) | six and twelve months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of beta cell function with a meal test | Changes in serum C-peptide levels (ng/mL) | six and twelve months after each therapy at times zero, 30, 60, 120 and 180 minutes after meal test | 
| improvement on alpha cell function with a meal test | Changes in plasma glucagon levels (pg/mL) | six and twelve months after each therapy at times zero, 30, 60, 120 and 180 minutes after meal test | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 2 diabetes, sitagliptin, NPH insulin, GLP-1