The Role of Endogenous Glucagon-like Peptide 1 (GLP-1) in Type 2 Diabetes Mellitus (T2DM)

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: exendin(9-39)amide; Other: duodenal meal; Drug: saline; Other: duodenal saline

• Registration Number: NCT01449019
• Lead Sponsor: Ludwig-Maximilians - University of Munich

Brief Summary

The purpose of the study is to determine the contribution of endogenous Glucagon-like peptide 1 (GLP-1) to the postprandial secretion of insulin and glucagon and the incretin effect in healthy subjects and patients with type 2 diabetes mellitus (T2DM).

Detailed Description

Not available

Study Timeline

• Study Start: 2006-12
• Primary Completion: 2007-08
• Study Completion: 2010-07
• Status Verified: 2011-10
• Study First Submitted: 2011-10-02
• Study First Submitted QC: 2011-10-05
• Last Update Submitted: 2011-10-05
• Study First Posted: 2011-10-07
• Last Update Posted: 2011-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• male or female (postmenopausal, surgically sterile or using double-barrier method of contraception) healthy subjects and patients with type 2 diabetes mellitus (T2DM)
• must be able to complete a 1 week wash-out of current anti-diabetic medications
• Age 30-70 years
• HbA1c (Hemoglobin A1c) ≤11% at screening
• Body mass index (BMI) <40 kg/m2
• Patients with type 2 diabetes mellitus (T2DM): Must have a fasting blood glucose of ≤12.2 mmol/L (240 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

Exclusion Criteria

• Patients with type 1 diabetes mellitus (T1DM), diabetes as a result of pancreatic injury, or secondary forms of diabetes (eg Cushing, acromegaly)
• 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).
• 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.
• history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• history or clinical evidence of pancreatic injury or pancreatitis;
• history or presence of impaired renal function as indicated by abnormal creatinine or urea val-ues or abnormal urinary constituents (e.g., albuminuria);
• evidence of urinary obstruction or difficulty in voiding at screening;
• Polymorphonuclears <1500/µL at inclusion or platelet count < 100,000/μL at screening and baseline.
• History of immunocompromise.
• Evidence of liver disease as indicated by abnormal transaminases and alkaline phosphatase exceeding twice the upper limit of the normal range, and serum bilirubin should not exceed the value of 27 µmol/L (1.6 mg/dL).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
intravenous infusion	exendin(9-39)amide	-
intravenous infusion	saline	-
intraduodenal perfusion	duodenal meal	-
intraduodenal perfusion	duodenal saline	-

Primary Outcome Measures

Name	Time	Method
The incretin effect	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	The incretin effect is the difference between postprandial plasma concentrations of insulin and C-peptide, respectively, and those during the isoglycemic fasting control experiment. The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.

Secondary Outcome Measures

Name	Time	Method
Plasma concentrations of glucagon	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.
Plasma concentrations of insulin	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.
Plasma concentrations of Glucagon-like peptide-1(7-36) (GLP-1(7-36))	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.
Plasma concentrations of C-peptide	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.
Plasma concentrations of Glucose-dependent insulinotropic polpypeptide (GIP)	Area Under Curve (AUC) Time Frame: from 0 to 90 minutes under duodenal meal perfusion	The AUC is calculated after priming intravenous infusion (saline or exendin(9-39)) and under steady state duodenal meal perfusion.

Trial Locations

Locations (2)

Ludwig Maximilians-University, Clinical Research Unit; 🇩🇪 Munich, Germany

Clinical Research unit, Dept. of Internal Medicine II - Großhadern, University of Munich; 🇩🇪 Munich, Germany