Trial Outcomes & Findings for Sitagliptin and the Risk for Hypoglycaemia in Type 2 Diabetes Patients (NCT NCT03359590)

Last Updated: 2021-02-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

during the two in-house periods (54 hs each) after treatment with sitagliptin or placebo for up to 24 weeks

Results posted on

2021-02-21

Participant Flow

Subjects were recruited by use of the site specific database

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

Participant milestones

Participant milestones
Measure	Sequence 1 First intervention: treatment with sitagliptin tablets (100 mg/day) for up to 24 weeks. Washout 4 weeks Second intervention: treatment with placebo tablets for up to 24 weeks.	Sequence 2 First intervention: treatment with placebo tablets for up to 24 weeks. Washout 4 weeks Second intervention: treatment with sitagliptin tablets (100 mg/day) for up to 24 weeks.
First Intervention STARTED	10	10
First Intervention Exposed	9	10
First Intervention Discontinued	1	2
First Intervention COMPLETED	9	8
First Intervention NOT COMPLETED	1	2
Second Intervention STARTED	9	8
Second Intervention Exposed	9	8
Second Intervention Discontinued	0	0
Second Intervention COMPLETED	9	8
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 First intervention: treatment with sitagliptin tablets (100 mg/day) for up to 24 weeks. Washout 4 weeks Second intervention: treatment with placebo tablets for up to 24 weeks.	Sequence 2 First intervention: treatment with placebo tablets for up to 24 weeks. Washout 4 weeks Second intervention: treatment with sitagliptin tablets (100 mg/day) for up to 24 weeks.
First Intervention Withdrawal by Subject	1	1
First Intervention Protocol Violation	0	1

Baseline Characteristics

Sitagliptin and the Risk for Hypoglycaemia in Type 2 Diabetes Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=20 Participants Drug: Sitagliptin or placebo The treatment consists of sitagliptin 100 mg/day or placebo for up to 24 weeks.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	15 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment Germany	20 participants n=93 Participants
Body mass index (BMI, kg/m2)	29.19 kg/m^2 STANDARD_DEVIATION 4.139 • n=93 Participants
Waist circumference (cm)	105.9 cm STANDARD_DEVIATION 9.02 • n=93 Participants
Height (cm)	178.1 cm STANDARD_DEVIATION 9.20 • n=93 Participants
Weight (kg)	92.32 kg STANDARD_DEVIATION 13.79 • n=93 Participants
HbA1c (%)	7.35 percent STANDARD_DEVIATION 0.661 • n=93 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sitagliptin Arm n=17 Participants Drug: Sitagliptin The treatment consists of sitagliptin 100 mg/day up to a maximum of 24 weeks.	Placebo Arm n=18 Participants Drug: Placebo The treatment consists of placebo up to a maximum of 24 weeks.
The Frequency of Hypoglycaemic Episodes With Sitagliptin vs Placebo Treatment.	5.35 Hypoglycaemic episodes Standard Deviation 4.137	5.72 Hypoglycaemic episodes Standard Deviation 3.045

Adverse Events

Sitagliptin Arm

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin Arm n=17 participants at risk Drug: Sitagliptin The treatment consists of sitagliptin 100 mg/day up to a maximum of 24 weeks.	Placebo Arm n=19 participants at risk Drug: Placebo The treatment consists of placebo up to a maximum of 24 weeks.
Cardiac disorders Coronary heart diesease	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.

Other adverse events

Additional Information

Dr. Christoph Kapitza

Profil Institut für Stoffwechselforschung GmbH

Phone: +49 2131 4018

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sitagliptin Arm n=17 participants at risk Drug: Sitagliptin The treatment consists of sitagliptin 100 mg/day up to a maximum of 24 weeks.	Placebo Arm n=19 participants at risk Drug: Placebo The treatment consists of placebo up to a maximum of 24 weeks.
Injury, poisoning and procedural complications Traumatic amputation	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	0.00% 0/19 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Investigations Electrocardiogram ST segment depression	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	10.5% 2/19 • Number of events 2 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Musculoskeletal and connective tissue disorders Fibromyalgia	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Gastrointestinal disorders Diarrhoea	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	21.1% 4/19 • Number of events 4 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Gastrointestinal disorders Nausea	17.6% 3/17 • Number of events 3 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Gastrointestinal disorders Vomiting	11.8% 2/17 • Number of events 3 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	10.5% 2/19 • Number of events 2 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Injury, poisoning and procedural complications Arthropod bite	11.8% 2/17 • Number of events 2 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Injury, poisoning and procedural complications Infusion site thrombosis	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	0.00% 0/19 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Injury, poisoning and procedural complications Decapitation	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Cardiac disorders Cardiovascular disorder	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Cardiac disorders Coronary artery disease	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Cardiac disorders Tachyarrhythmia	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	0.00% 0/19 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Cardiac disorders Ventricular extrasystoles	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Ear and labyrinth disorders Ear discomfort	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Musculoskeletal and connective tissue disorders Intervertebral disc displacement	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Musculoskeletal and connective tissue disorders Muscle contractions involuntary	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	0.00% 0/19 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Nervous system disorders Allodynia	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	0.00% 0/19 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Nervous system disorders Dizziness	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 4 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Nervous system disorders Headache	35.3% 6/17 • Number of events 6 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	15.8% 3/19 • Number of events 3 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Psychiatric disorders Sleep disorder	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Respiratory, thoracic and mediastinal disorders Rhinitis	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Vascular disorders Orthostatic intolerance	5.9% 1/17 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	0.00% 0/19 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.
Vascular disorders Syncope	0.00% 0/17 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.	5.3% 1/19 • Number of events 1 • For each participant from baseline to end of trial, with a range from 7-53 weeks per participant, on average 11 weeks In this report, only treatment-emergent adverse events (TEAEs) are reported, occurring after randomisation. No AEs were reported for the washout period.