SAFEGUARD: Safety Evaluation of Adverse Reactions in Diabetes

Sponsor

Charles University, Czech Republic (Other)

Overall Status

Completed

CT.gov ID

NCT02092597

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effects of incretin-based antidiabetic therapies (DPP-4 inhibitors and GLP-1 agonists) on cardiovascular, gastrointestinal and renal system and to detail the mechanisms underlying their action in these systems.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Exenatide Drug: Linagliptin Drug: Gliclazide	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Oct 1, 2013

Actual Primary Completion Date :

Oct 1, 2015

Actual Study Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GLP-1 agonist Exenatide 5 ug s.c. bid for the 1st month, 10 ug s.c. bid for the next 2 months	Drug: Exenatide
Active Comparator: DPP-4 inhibitor Linagliptin 5 mg tbl qd for 3 months	Drug: Linagliptin
Active Comparator: Sulfonylurea derivate Gliclazid 30 mg tbl qd for 3 months	Drug: Gliclazide

Arm

Intervention/Treatment

Active Comparator: GLP-1 agonist

Exenatide 5 ug s.c. bid for the 1st month, 10 ug s.c. bid for the next 2 months

Drug: Exenatide

Active Comparator: DPP-4 inhibitor

Linagliptin 5 mg tbl qd for 3 months

Drug: Linagliptin

Active Comparator: Sulfonylurea derivate

Gliclazid 30 mg tbl qd for 3 months

Drug: Gliclazide

Outcome Measures

Primary Outcome Measures

Heart rate [90 days after treatment initiation]
Gastric evacuation velocity [90 days after treatment initiation]
Blood pressure [90 days after treatment initiation]
Left ventricular ejection fraction [90 days after treatment initiation]
Intimomedial thickness [90 days after treatment initiation]
Pulse wave velocity [90 days after treatment initiation]
Glomerular filtration rate [90 days after treatment initiation]
Tubular function [90 days after treatment initiation]
KIM-1 [90 days after treatment initiation]
Marker of renal damage
Exocrine pancreas function [90 days after treatment initiation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 2 diabetes mellitus
Metformin monotherapy - stable dose during last 3 months
HbA1C 48-75 mmol/mol (IFCC)
BMI 25-40 kg/m2
Age 35-70 years (women postmenopausal)
Use of ACE inhibitors or ATII receptor blockers for at least 3 months before enrollment

Exclusion Criteria:

eGFR<30 ml/min/1.73m2 (MDRD)
Treatment with incretin mimetics during 3 months before enrollment
Chronic insulin therapy
Chronic use of loop diuretics, glucocorticoids, NSAID, immune suppressants, antimicrobial agents, chemotherapeutics, bile acid sequestrants (colestyramin, colesevelam)
History of pancreatic disease or impaired pancreatic function (defined as the need to use pancreatic enzymes)
Active liver disease or a 3-fold elevation of liver transaminases (ALT, AST)
Active malignancy
History of severe cardiovascular disease including acute coronary syndrome, stroke or transient ischemic neurologic disorder during previous 6 months, atrial fibrillation or other arrhythmia requiring chronic antiarrhythmic medication, chronic heart failure (New York Heart Association grade III/IV)
History of alcohol abuse, defined as >4 units of alcohol/day (32 g or 40 ml of 100% alcohol)
History of allergy for GLP-1 receptor agonists or DPP-4 inhibitors
Any disease that could interfere with study procedures (e.g. decreased mobility, mental incapacity)
Inability to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	General University Hospital	Prague		Czechia	128 08

Sponsors and Collaborators

Charles University, Czech Republic

Investigators

Principal Investigator: Martin Haluzik, MD DSc, 3rd Department of Medicine, General University Hospital and Charles University 1st Faculty of Medicine