Antidiabetic Effects of Adding a DPP-4 Inhibitor to Pre-Existing Treatment With an Incretin Mimetic in Patients With T2D

NCT01937598 | Completed Phase 3 Results

• 2 other identifiers: 120-0569-DZBL-20122013-001764-35
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin

Conditions

Type 2 Diabetes

Keywords

Incretin, DPP-4 inhibitor

Outcome Measures

Primary Outcomes (1)

• Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)

  Incremental area under the plasma glucose (BG) concentration-time profile (AUC) immediately before to 300 min after a mixed meal test. In addition, the time course of BG values will be analysed with an ANCOVA model for repeated measurements with placebo baseline values as covariate. Time points to create the curce were 0, 15, 30, 45, 60, 90, 120, 150, 180, 240 and 300 minutes post mixed meal test.

  0 to 300 min post mixed meal test

Secondary Outcomes (8)

• AUC Plasma Glucose

  Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)

• AUC Insulin

  Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)

• AUC C-peptide

  Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)

• AUC Glucagon

  Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)

• AUC Total GLP-1

  Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)

Study Arms (2)

Sitagliptin, then Placebo

EXPERIMENTAL

Drug: Placebo; Other: Mixed meal test; Drug: Liraglutide; Drug: Sitagliptin

Placebo, then Sitagliptin

EXPERIMENTAL

Drug: Placebo; Other: Mixed meal test; Drug: Liraglutide; Drug: Sitagliptin

Interventions

Placebo DRUG

Patients administered a single dose of placebo during a mixed meal challenge.

Placebo, then Sitagliptin; Sitagliptin, then Placebo

Mixed meal test OTHER

Subjects will be instructed to consume the mixed meal test within 20 minutes. The exact start and stop time of the mixed meal test consumption will be recorded in the CRF. The mixed meal test procedures will be identical for all subjects randomised in the study. To detect the plasma glucose excursion after mixed meal test, plasma glucose will be closely monitored

Placebo, then Sitagliptin; Sitagliptin, then Placebo

Liraglutide DRUG

Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week) that will be continued for the entire duration of the study.

Also known as: Victoza

Placebo, then Sitagliptin; Sitagliptin, then Placebo

Sitagliptin DRUG

Patients administered a single dose of Sitagliptin during a mixed meal challenge.

Placebo, then Sitagliptin; Sitagliptin, then Placebo

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed \& dated written informed consent
• Male \& female subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening
• Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator
• On a stable regimen of metformin for at least 1 month and liraglutide 1.2 mg for at least 1 week at the time-point of randomisation.
• Age: 25 - 75 years, both inclusive
• Body mass index (BMI): 22 - 40kg/m\^2, both inclusive
• HbA1c ≥ 6.5 and ≤ 8.5% (≥ 7.0 and ≤ 8.5% for patients without previous liraglutide treatment)
• Female must be post-menopausal, surgically sterilized or practicing an effective birth control

You may not qualify if:

• Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis
• Current or previous treatment with insulin therapy (except for treatment at diabetes' diagnosis, within a clinical trial, for surgical procedures or during an acute illness, and no insulin administration within the 6 months before screening)
• Treatment with any hypoglycaemic medication other than metformin and liraglutide within one month prior to screening
• Known of diabetic gastroparesis and / or prokinetic therapy
• Subjects that underwent surgery of the upper gastrointestinal tract
• Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods
• Any severe medical or surgical history of conditions likely to confound study assessments or study endpoints, for example but not limited to haemoglobinopathies, inflammatory bowel disease, cystic fibrosis, bariatric surgery and/or any surgery shortening the intestine, history of lactose intolerance, lactose- or glucose-galactose-malabsorption
• A suspicion of medullary thyroid cancer or a multiple endocrine neoplasia
• A personal or family history of medullar thyroid cancer or a multiple endocrine neoplasia
• Serious and/or unstable coronary heart disease (unstable angina, myocardial infarction within the preceding 6 months), congestive heart failure of New York Heart Association Class III or worse (severe limitation of physical activity; physical activity of low intensity resulting in fatigue, palpitation, or dyspnoea), second/third degree heart block, superior vena cava syndrome, uncontrolled hypertension, history of congenital QT-syndrome within family, history of stroke (within the preceding 6 months) or serious peripheral vascular disease
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (grade 3), left bundle branch block, or asymptomatic sustained ventricular tachycardia are not allowed
• Marked diabetic complications: severe autonomic or sensory neuropathy including previously diagnosed gastroparesis; proliferative retinopathy
• Any respiratory disease leading to respiratory insufficiency and/or depression including but not limited to clinically significant: bronchial asthma, chronic obstructive pulmonary disease, that might impact to the breath test, as judged by the investigator
• Clinically significant vital signs including known bradycardia with pulse rate \< 50/min or 12-lead ECG findings including QTc (corrected QT interval) \> 450 msec for males or QTc \> 470 msec for women
• Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the Investigator

Sponsors & Collaborators

• Michael A. Nauck: lead

Study Sites (1)

Diabeteszentrum Bad Lauterberg

Bad Lauterberg im Harz, 37431, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Limitations and Caveats

Results may not be interpretable for combinations of other DPP-4 Inhibitors than sitagliptin in combination with other (especially short-acting) GLP-1 receptor agonists

Results Point of Contact

• Title: Prof. Dr. M. A. Nauck, Principle Investigator
• Organization: Div. Diabetology, Med. Dep. I, St. Josef-Hospital (Ruhr-Univeristy Bochum), change of address 01.01.20015

michael.nauck@rub.de

+49-234-509

Study Officials

• Michael A. Nauck, Prof. Dr.

  Diabeteszentrum Bad Lauterberg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: September 9, 2013
• Study Start: August 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: June 1, 2015
• Last Updated: January 30, 2017
• Results First Posted: January 30, 2017

Record last verified: 2016-12

Locations

DE (1)