This trial is active, not recruiting.

Conditions type 2 diabetes, coronary artery disease
Treatments linagliptin, placebo
Phase phase 4
Sponsor Medical University of Graz
Start date July 2013
End date November 2016
Trial size 42 participants
Trial identifier NCT02350478, HS-2012-01


This study is planned to evaluate if linagliptin can improve endothelial function in patients with type 2 diabetes mellitus. In addition, the effect of linagliptin on arginine bioavailability ratios and postchallenge glycaemic control will be studied.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
(Active Comparator)
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
linagliptin Trajenta
The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
(Placebo Comparator)
The subjects will receive placebo.
placebo sugar pill
The subject will receive placebo orally once daily for 12 weeks.

Primary Outcomes

Changes in endothelial function (assessed by flow mediated dilatation - FMD)
time frame: 12 weeks

Secondary Outcomes

Changes in arginine bioavailability ratios
time frame: 12 weeks
Changes in biochemical markers of endothelial function
time frame: 12 weeks
Changes in the Area under Curve (AUC) of glucose, insulin and free fatty acids during the meal tolerance test
time frame: 12 weeks

Eligibility Criteria

Male or female participants from 40 years up to 80 years old.

Inclusion Criteria: - Age: 40 to 80 years - Early diabetes (postchallenge diabetes (2h glucose >200 mg/dl or type 2 diabetes treated with diet only or on a stable dose of metformin monotherapy) - Coronary atherosclerosis (diagnosed via coronary angiography or coronary computer tomography) Exclusion Criteria: - Acute coronary syndrome or cerebrovascular event within the previous 4 weeks - Body Mass Index (BMI) > 35 kg/m2 - HbA1c <6.0% (42 mmol/mol) - Serum creatinine > 2.5 mg/dl - Aspartate Transaminase (AST)/Alanine Transaminase (ALT)>3x upper limit of normal - HbA1c >9.0% (>75 mmol/mol) - Heart failure > New York Heart Association (NYHA) class II - Uncontrolled hypertension (blood pressure > 165 / 100 mmHg) - Treatment with orally administered steroids - New onset statin or Angiotensin Converting Enzym- (ACE-) inhibitor within the previous 6 weeks - Known Malignancy - Pregnancy or breast feeding women.

Additional Information

Official title Effects of Linagliptin on Endothelial Function and Global Arginine Bioavailability Ratio in Coronary Artery Disease Patients With Early Diabetes
Principal investigator Harald Sourij, Assoc.-Prof.
Description Patients with type 2 diabetes (T2DM) are at increased risk of macrovascular events as well as microvascular complications. It is well known, that the pathophysiologic process of type 2 diabetes starts many years before the diagnosis can be made on the basis of elevated fasting blood glucose. In particular the data of the United Kingdom Prospective Diabetes Study (UKPDS) study and the UKPDS post trial monitoring highlighted the importance of an early glucose lowering intervention in patients with T2DM with respect to micro- and macrovascular complications. The investigators and in particular the Euro Heart survey on Diabetes and the Heart demonstrated, that in a cardiovascular high risk population, namely patients with coronary artery disease (CAD), about 35% suffer from manifest type 2 diabetes. In addition, another 9 to 15% of CAD patients have postchallenge diabetes, diagnosed on the basis of an oral glucose tolerance test, which means that approximately a half of all patients with CAD have diabetes. Recently the investigators could demonstrate that not only established type 2 diabetes diagnosed on the basis of fasting hyperglycaemia is associated with an increased cardiovascular risk, but also postchallenge hyperglycemia (i.e. impaired glucose tolerance or postchallenge diabetes). Dipeptidylpeptidase-4 (DPP-4) inhibitors increase endogenous glucagon like-peptide-1 (GLP-1) levels and GLP-1 in turn increases the insulin release from pancreatic beta-cells in a glucose dependent manner as well as suppresses glucagon secretion from pancreatic alpha cells. Investigations in type 2 diabetic patients showed that this drug class lowers both, fasting and postchallenge or postmeal glucose levels and hence, HbA1c and is well tolerated. However, the lowering of the surrogate measurement HbA1c has not necessarily turned out to translate into a reduced number of cardiovascular events in patients with T2DM. In contrary in particular for the thiazolidinedione Rosiglitazone concerns about an increased risk of cardiovascular events have been raised despite a robust HbA1c lowering effect.Therefore the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued in 2008 and 2010, respectively, guidance for new glucose lowering drugs, requiring proof of at least cardiovascular safety. Cardiovascular outcome trials with Linagliptin are currently being performed (CAROLINA, CARMELINA), however, it will take a couple of years until the results are available.A well known and validated cardiovascular surrogate parameter is endothelial dysfunction. The investigators and others have shown previously, that endothelial dysfunction is present in patients with coronary artery disease and early diabetes and can be improved by pharmacological intervention. This surrogate measurement could be helpful in better understanding the cardiovascular effects of Linagliptin while awaiting the results of the definitive outcome trials. The aim of this study is to investigate the effects of Linagliptin in coronary patients with early T2DM on various cardiovascular surrogate measurements including mechanical and biochemical endothelial function assessments. The overarching aim of our study is to investigate the effects of Linagliptin on endothelial function, arginine bioavailability ratios and postchallenge glycaemic control in patients with early diabetes and coronary atherosclerosis.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Medical University of Graz.