Effect of Sitagliptin on Incretin Effect in Patients With Type 2 Diabetes Mellitus

NCT00551590 | Completed Phase 1 DMC

• 2 other identifiers: SITEX-02EudraCT 2007-001050-83
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of the DPP-4 inhibitor sitagliptin on the incretin effect in patients with type 2 diabetes mellitus.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes mellitus; DPP-4 inhibitor; sitagliptin; exendin(9-39); GLP-1

Outcome Measures

Primary Outcomes (1)

• To asses the effect of sitagliptin compared to placebo and to coadministration of sitagliptin and the GLP-1 receptor antagonist exendin(9-39)NH2 on the incretin effect after an oral glucose challenge.

  during 240 minutes after ingestion of an OGTT

Secondary Outcomes (1)

• Plasma glucagon, plasma GIP, plasma GLP-1, Insulin, C-peptide, plasma glucose profiles. 13CO2 exhalation kinetics assessing gastric emptying

  during 240 minutes after ingestion of an OGTT

Study Arms (4)

1

PLACEBO COMPARATOR

placebo PO (placebo control for sitagliptin) for three days. Saline IV (placebo control for exendin(9-39) on two consecutive study days.

Drug: Placebo tablet; Drug: Saline infusion

2

EXPERIMENTAL

Sitagliptin 100 mg PO for three days. Saline IV (placebo control for exendin(9-39)) on two consecutive study days

Drug: Sitagliptin tablet; Drug: Saline infusion

3

EXPERIMENTAL

Sitagliptin 100 mg PO for three days. Exendin(9-39) IV on two consecutive study days.

Drug: Sitagliptin tablet; Drug: Exendin(9-39) infusion

4

PLACEBO COMPARATOR

placebo PO (placebo control for sitagliptin) for three days. Exendin(9-39)IV on two consecutive study days.

Drug: Placebo tablet; Drug: Exendin(9-39) infusion

Interventions

Placebo tablet DRUG

placebo PO (placebo control for sitagliptin) for three days

1; 4

Sitagliptin tablet DRUG

Sitagliptin 100 mg PO for three days.

2; 3

Saline infusion DRUG

Saline IV (placebo control for exendin(9-39)) on two consecutive study days

1; 2

Exendin(9-39) infusion DRUG

Exendin(9-39) IV on two consecutive study days.

3; 4

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with T2DM without childbearing potential
• Male patients with T2DM using a double-barrier method of contraception
• must be able to complete a 1 week wash-out of current anti-diabetic medications (patients on PPARγ must be off for at least 4 weeks)
• no medications which may alter gastric motility (i.e. acetaminophen, erythromycin) except for cardiac medication at a stable dose.
• Age 30-70 years
• HbA1c ≤9% at screening
• BMI\<40 kg/m2
• Must have a fasting blood glucose of ≤11.1 mmol/L (200 mg/dL) at screening
• Able to provide written informed consent prior to study participation
• Able to communicate well with the investigator and comply with the requirements of the study
• Able to maintain dietetic restrictions and to perform measurements of blood glucose on a daily basis (fasting and two-hours postprandial). Patients must be informed the investigator if fasting glucose is above 200mg/dl or two hours postprandially blood glucose concentration above 240mg/dl is being measured.

You may not qualify if:

• T1DM, diabetes as a result of pancreatic injury, or secondary forms of diabetes (eg. Cushing, acromegaly)
• Females with childbearing potential, breastfeeding and pregnant women
• Need for insulin within the previous 3 months
• Use of Thiazolidinediones in the previous 4 weeks
• Significant concomitant disease or complications of diabetes (i.e. nephropathy, autonomic dysfunction, orthostasis).
• Fasting triglycerides \>5.1 mmol/L (\>450 mg/dL) within the past 4 weeks.
• Treatment with systemic steroids and thyroid hormone (unstable dosage).
• Patients with any history of gastrointestinal surgery, e.g. partial bowel resections, partial gastric resections, etc.
• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
• Significant illness within the two weeks prior to dosing.
• Past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.
• History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following:
• history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich

Munich, 81377, Germany

Location

Related Publications (4)

• Schirra J, Sturm K, Leicht P, Arnold R, Goke B, Katschinski M. Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans. J Clin Invest. 1998 Apr 1;101(7):1421-30. doi: 10.1172/JCI1349.

  PMID: 9525985 BACKGROUND

• Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, Goke B. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006 Feb;55(2):243-51. doi: 10.1136/gut.2004.059741. Epub 2005 Jun 28.

  PMID: 15985560 BACKGROUND

• Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280.

  PMID: 3514343 BACKGROUND

• Aulinger BA, Bedorf A, Kutscherauer G, de Heer J, Holst JJ, Goke B, Schirra J. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes. 2014 Mar;63(3):1079-92. doi: 10.2337/db13-1455. Epub 2013 Dec 2.

  PMID: 24296715 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Sitagliptin Phosphate; exendin (9-39)

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Joerg Schirra, MD

  Clinical Research Unit, Dept. of Internal Medicine II, University of Munich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: October 30, 2007
• First Posted: October 31, 2007
• Study Start: December 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: September 1, 2011
• Last Updated: October 4, 2011

Record last verified: 2011-10

Locations

DE (1)