Pharmacological Action
Conditions
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.
Interventions
The treatment consists of sitagliptin tablets (100 mg/day) for up to 24 weeks.
DRUGPlacebo
The treatment consists of placebo tablets for up to 24 weeks.
Sponsors
Merck Sharp & Dohme LLC
Profil Institut für Stoffwechselforschung GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
This is a double-blind randomised trial. Except for the unblinded persons involved in the preparation of the IMP (these persons are not involved in any other trial activities), everyone involved in the trial will be blinded until completion of the trial and the final data review.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency of Hypoglycaemic Episodes With Sitagliptin vs Placebo Treatment. | during the two in-house periods (54 hs each) after treatment with sitagliptin or placebo for up to 24 weeks | 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. |
Countries
Germany
Participant flow
Recruitment details
Subjects were recruited by use of the site specific database
Pre-assignment details
All subjects underwent outpatient insulin titration during each treatment period. The aim was to find the insulin dose that, under these conditions, stabilised individual fasting plasma glucose for at least one week
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Drug: Sitagliptin or placebo
The treatment consists of sitagliptin 100 mg/day or placebo for up to 24 weeks. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Protocol Violation | 0 | 1 |
| First Intervention | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Body mass index (BMI, kg/m2) | 29.19 kg/m^2 STANDARD_DEVIATION 4.139 |
| HbA1c (%) | 7.35 percent STANDARD_DEVIATION 0.661 |
| Height (cm) | 178.1 cm STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment Germany | 20 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
| Waist circumference (cm) | 105.9 cm STANDARD_DEVIATION 9.02 |
| Weight (kg) | 92.32 kg STANDARD_DEVIATION 13.79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 19 |
| other Total, other adverse events | 12 / 17 | 11 / 19 |
| serious Total, serious adverse events | 0 / 17 | 1 / 19 |
Outcome results
Primary
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.
Time frame: during the two in-house periods (54 hs each) after treatment with sitagliptin or placebo for up to 24 weeks
Population: The per protocol analysis set comprised all subjects completing the trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin Arm | The Frequency of Hypoglycaemic Episodes With Sitagliptin vs Placebo Treatment. | 5.35 Hypoglycaemic episodes | Standard Deviation 4.137 |
| Placebo Arm | The Frequency of Hypoglycaemic Episodes With Sitagliptin vs Placebo Treatment. | 5.72 Hypoglycaemic episodes | Standard Deviation 3.045 |