Sitagliptin and the Risk for Hypoglycaemia in Type 2 Diabetes Patients

Study Overview
=================
Brief Summary
-----------------
Sitagliptin, through its effects on sensitizing alpha-cell sensitivity to glucose, can initiate counter-regulatory glucagon responses at higher glycemic thresholds, thus reducing the number of clinically apparent hypoglycemic episodes, and/or ameliorating the severity of hypoglycemic episodes in the case that they should occur. The endpoints have defined such that consequences of this hypothesis can be measured.

Official Title
-----------------
DPP-4 Inhibition With Sitagliptin and the Risk for Hypoglycaemia in the Fasting State in Subjects With Type 2 Diabetes Treated to Fasting Plasma Glucose Targets With Insulin Glargine and Metformin

Conditions
-----------------
Pharmacological Action

Intervention / Treatment
-----------------
* Drug: Sitagliptin 100 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subject with diabetes mellitus type 2. Age between 18 and 64 years, both inclusive. HbA1c <= 8.5%. Stable treatment with insulin glargine (any dose) and metformin (>= 1500 mg/day or at highest tolerated dose) for at least 3 months prior to inclusion into the trial with or without additional oral glucose-lowering agents (except thiazolidinediones). Considered generally healthy (apart from diabetes mellitus type 2 and associated conditions such as hypertension, hyperlipidaemia and hyperuricaemia) upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator. Exclusion Criteria: Known or suspected hypersensitivity to sitagliptin or related products. More than one episode of severe hypoglycaemia with seizure, coma or requiring medical assistance of another person during the past 6 months or hypoglycaemic unawareness as judged by the Investigator. Current or previous treatment (less than 3 months prior to screening) with insulin products other than insulin glargine and/or with Glucagon-like peptide (GLP) 1 receptor agonists and/or with thiazolidinediones. Unwillingness to wash-off any oral glucose-lowering agents other than metformin.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 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: Crossover Assignment
Interventional Model Description: This is a postmarketing phase 2 trial. The trial is designed as single centre, randomised, double blind, two-way treatment, placebo controlled crossover trial in subjects with type 2 diabetes mellitus treated to fasting plasma glucose targets with insulin glargine and metformin.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin arm<br>Sitagliptin 100 mg | Drug: Sitagliptin 100 mg<br>* The treatment consists of sitagliptin tablets (100 mg/day) for up to 24 weeks.<br>|
| Placebo Comparator: Placebo arm<br>Placebo comparator | Drug: Placebo<br>* The treatment consists of placebo tablets for up to 24 weeks.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Frequency of Hypoglycaemic Episodes With Sitagliptin vs Placebo Treatment. | The purpose of the trial was to test the influence of DPP-4 inhibition on the risk to develop hypoglycaemia. Chemical hypoglycaemic episodes (characterised by a plasma glucose nadir ≤70 mg/dL) occurring during the in-house periods of the subjects were compared. | during the two in-house periods (54 hs each) after treatment with sitagliptin or placebo for up to 24 weeks |