Effects of Saxagliptin on Endothelial Function

NCT01319357 | Completed Phase 3 DMC

• 1 other identifier: SAXA24011980GLIPTIN
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus Type 2

Outcome Measures

Primary Outcomes (1)

• effect of saxagliptin compared to placebo on endothelial and vascular function of the retinal circulation

  retinal circulation. By applying Scanning-Laser-Doppler-Flowmetry, the change of retinal capillary flow after i.v. L-NMMA application

  after 6 weeks of treatment with saxagliptin vs. 6 weeks of treatment with placebo (12 weeks in all)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Saxagliptin

ACTIVE COMPARATOR

saxagliptin 5 mg/day during 6 weeks

Drug: Saxagliptin

Interventions

Saxagliptin DRUG

orally 5 mg/d for 6 weeks

Also known as: Onglyza

Saxagliptin

Placebo DRUG

orally for 6 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg

Erlangen, 91054, Germany

Location

Related Publications (3)

• Ott C, Raff U, Schmidt S, Kistner I, Friedrich S, Bramlage P, Harazny JM, Schmieder RE. Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes. Cardiovasc Diabetol. 2014 Jan 14;13:19. doi: 10.1186/1475-2840-13-19.

  PMID: 24423149 RESULT

• Staef M, Ott C, Kannenkeril D, Striepe K, Schiffer M, Schmieder RE, Bosch A. Determinants of arterial stiffness in patients with type 2 diabetes mellitus: a cross sectional analysis. Sci Rep. 2023 Jun 2;13(1):8944. doi: 10.1038/s41598-023-35589-4.

  PMID: 37268640 DERIVED

• Kannenkeril D, Bosch A, Harazny J, Karg M, Jung S, Ott C, Schmieder RE. Early vascular parameters in the micro- and macrocirculation in type 2 diabetes. Cardiovasc Diabetol. 2018 Sep 19;17(1):128. doi: 10.1186/s12933-018-0770-4.

  PMID: 30231923 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

saxagliptin

Condition Hierarchy (Ancestors)

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

Study Officials

• Roland E Schmieder, MD

  University of Erlangen-Nürnberg

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 21, 2011
• Study Start: October 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: February 12, 2014

Record last verified: 2014-02

Locations

DE (1)