Effects of Saxagliptin on Endothelial Function

• Status: Completed
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Diabetes mellitus is a metabolic disease with a growing prevalence worldwide. Currently available therapies for type 2 diabetes have various limitations and are associated with increased risk of hypoglycemia, weight gain, gastrointestinal side effects or edema and heart failure.

A new and promising class of drugs are the gliptins. Several efficacy studies demonstrated a significant improvement of HbA1c with gliptins. In addition, gliptins improved fasting as well as prandial glucose levels and did not induce weight gain. Due to these positive metabolic effects in combination with a very small spectrum of side effects gliptins might very well be part of the standard therapy for type 2 diabetes in the future.

Apart form surrogate parameters like reduction of fasting and postprandial blood glucose levels or improvement of HbA1c, the effect of gliptins on micro- and macrovascular function and cardiovascular outcome has not been the primary focus of current studies. Diabetes mellitus is strongly associated with microangiopathy and macroangiopathy and is a strong independent risk factor for cardiovascular disease and cardiovascular mortality. Endothelial dysfunction which plays a crucial role in the atherosclerotic process is commonly observed in patients with diabetes mellitus and already prediabetes and has - amongst other factors - been linked to fasting and postprandial hyperglycemia. Taken into account that gliptins reduce hyperglycemia and hyperglycemic peaks by preventing inactivation of GLP-1, which exerted beneficial effects on the endothelium in previous studies it is of major interest whether therapy with gliptins improves endothelial function.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Erlangen-Nürnberg Medical School
• Treatments: Saxagliptin

Criteria

Inclusion criteria:

• Type 2 diabetes mellitus defined by fasting glucose ≥126 mg/dl or HbA1c ≥6.5% or on blood glucose lowering medication

• Age of 18 - 75 years

• Male and Female patients are eligible. Females of child bearing potential or within two years of the menopause are only eligible if pregnancy test at the screening visit is negative and they use adequate contraceptive precautions during the trial.

• The patient must demonstrate that she/he is able and willing to perform blood glucose measurements as necessary for Home Blood Glucose Monitoring by herself/himself after it was demonstrated to her/him.

Exclusion Criteria:

• Any other form of diabetes mellitus than type 2 diabetes mellitus

• Patients with more than on one blood glucose lowering medication or on insulin therapy

• Last measured HbA1c > 11%

• Blood pressure levels ≥180/110 mmHg

• Body mass index >50 kg/m²

• Triglyceride levels >1000 mg/dl

• HDL-cholesterol levels <25 mg/dl

• Estimated creatinine clearance < 50 ml/min/1.73m²

• Macroalbuminuria defined by urinary albumine-to-creatinine ratio > 300 mg/g

• Known liver function test >3 times upper limit of normal

• Pregnant or breast-feeding patients

• Current or previous (within 6 months) treatment with an incretin-based therapy such as DPP 4 inhibitors and/or GLP-1 mimetics

• Any patient currently receiving chronic (>30 consecutive days) treatment with an oral corticosteroid

• Acute cardiovascular event (including myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure, stroke, TIA. PRIND, intracerebral bleeding) <6 months prior to screening visit (visit 1)

• Diabetic retinopathy

• History of epilepsia or history of seizures

• Patients being treated for severe auto immune disease e.g. lupus

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and BMS or representative staff and/or staff at the study site)

• Previous randomisation in the present study

• Participation in another clinical study within 30 days prior to visit 1

• Individuals at risk for poor protocol or medication compliance

• Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V