Renal Effects of DPP-4 Inhibitor Linagliptin in Type 2 Diabetes - Full Text View

Purpose

The aim of this study is to detail the (mechanisms underlying the) actions of the DPP-4 inhibitor linagliptin on the renal system in patients with type 2 diabetes mellitus.

Condition	Intervention	Phase
Type 2 Diabetes	Drug: Linagliptin 5 mg QD (N=24) Drug: Glimepiride 1 mg QD (N=24)	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 4, Monocenter, Randomized, Double-blind, Comparator-controlled, Parallel-group, Mechanistic Intervention Trial to Assess the Effect of 8-week Treatment With the Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Linagliptin Versus the Sulfonylurea (SU) Derivative Glimepiride on Renal Physiology and Biomarkers in Metformin-treated Patients With Type 2 Diabetes Mellitus (T2DM)

Resource links provided by NLM:

Drug Information available for: Glimepiride Linagliptin

U.S. FDA Resources

Further study details as provided by M.H.H. Kramer, VU University Medical Center:

Primary Outcome Measures:

Changes from baseline following 8-week treatment with linagliptin vs glimepiride on fasting and postprandial renal hemodynamics, measured as GFR / ERPF (determined by inulin/para-aminohippuric-acid clearance) [ Time Frame: 8 weeks ]

Secondary Outcome Measures:

Renal tubular function [ Time Frame: 8 weeks ]
Renal damage, measured by urine biomarkers [ Time Frame: 8 weeks ]
Blood Pressure and Heart Rate [ Time Frame: 8 weeks ]

Other Outcome Measures:

Body anthropometrics: body weight, height, body mass index, waist circumference [ Time Frame: 8 weeks ]
Body fat content [ Time Frame: 8 weeks ]
Systemic hemodynamic variables (blood pressure, heart rate, stroke volume, cardiac output/-index, total systemic vascular resistance) [ Time Frame: 8 weeks ]
Derived from non-invasive beat-to-beat finger blood pressure measurements
Cardiac autonomic nervous system function [ Time Frame: 8 weeks ]
Microvascular function [ Time Frame: 8 weeks ]
Arterial stiffness [ Time Frame: 8 weeks ]
Glycemic variables [ Time Frame: 8 weeks ]
Glycated hemoglobin (HbA1c) and fasting glucose
Lipid spectrum [ Time Frame: 8 weeks ]
DPP4- and ACE activity [ Time Frame: 8 weeks ]


Enrollment:	48
Study Start Date:	March 2014
Study Completion Date:	April 2016
Primary Completion Date:	April 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Linagliptin 5 mg QD (N=24) Linagliptin 5 mg will be taken orally, once daily for 8 weeks	Drug: Linagliptin 5 mg QD (N=24) Linagliptin 5 mg will be taken orally, once daily for 8 weeks Other Name: Trajenta
Active Comparator: Glimepiride 1 mg QD (N=24) Glimepiride 1 mg will be taken orally, once daily for 8 weeks	Drug: Glimepiride 1 mg QD (N=24) Glimepiride 1 mg will be taken orally, once daily for 8 weeks Other Name: Amaryl

Detailed Description:

Based on preclinical and small-sized studies in non-diabetic individuals, incretin-based therapies, i.e. glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i), may hold promise in preventing the onset and progression of diabetic kidney disease. However, the potential renoprotective effects of these agents, that are believed to be effectuated "beyond glucose control", have not been sufficiently detailed in human diabetes.

Therefore, the present study aims to explore the mechanistic and clinical effects of DPP-4i on fasting and postprandial renal physiology and biomarkers in patients with type 2 diabetes.

Forty-eight patients with type 2 diabetes will undergo an eight week intervention with linagliptin or glimepiride in order to assess changes in the outcome parameters.

Eligibility


Ages Eligible for Study:	35 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with type 2 diabetes (HbA1c: 6.5-9.0% DCCT or 48-75 mmol/mol IFCC)
Metformin monotherapy; using a stable dose for at least 3 months prior to inclusion
Both genders (females must be post-menopausal)
Caucasian
Age: 35-75 years
Body Mass Index: >25 kg/m2
All patients with previously diagnosed hypertension should use a RAS-interfering agent (angiotensin converting enzyme inhibitor/angiotensin II receptor blocker) for at least 3 months

Exclusion Criteria:

Current / chronic use of the following medication: thiazolidinediones, insulin, glucocorticoids, immune suppressants, antimicrobial agents or chemotherapeutics. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study
Chronic use of NSAIDs will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications. However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
Pregnancy
Frequent occurrence of (confirmed) hypoglycemia (plasma glucose <3.9 mmol/L)
Estimated Glomerular Filtration Rate < 60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
Current urinary tract infection and active nephritis
Recent (<6 months) history of cardiovascular disease, including: acute coronary syndrome, chronic heart failure (New York Heart Association grade II-IV), stroke, transient ischemic neurologic disorder
Complaints compatible with or established gastroparesis and/or neurogenic bladder
Active liver disease
History of or actual pancreatic disease
History of or actual malignancy (except for basal cell carcinoma)
History of or actual severe mental disease
Substance abuse (alcohol: defined as >4 units/day; smoking/nicotine: defined as daily smoking/use)
Allergy to any of the agents used in the study
Inability to understand the study protocol or give informed consent

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02106104

Locations


Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV

Sponsors and Collaborators

VU University Medical Center

Investigators


Principal Investigator:	Mark Kramer, MD PhD	VU University Medical Center

More Information


Responsible Party:	M.H.H. Kramer, MD PhD, VU University Medical Center
ClinicalTrials.gov Identifier:	NCT02106104 History of Changes
Other Study ID Numbers:	DC2013RENALIS U1111-1143-9518 ( Other Identifier: Universal Trial Number ) 2013-002493-47 ( EudraCT Number ) NL47157.029.13 ( Registry Identifier: CCMO )
Study First Received:	March 28, 2014
Last Updated:	May 16, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by M.H.H. Kramer, VU University Medical Center:


Type 2 diabetes mellitus Diabetic kidney disease Diabetic nephropathy Renoprotection	DPP-4 inhibitors Linagliptin SU derivatives Glimepiride

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Glimepiride Linagliptin Dipeptidyl-Peptidase IV Inhibitors Anti-Arrhythmia Agents Hypoglycemic Agents	Physiological Effects of Drugs Immunosuppressive Agents Immunologic Factors Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 17, 2017

Renal Effects of DPP-4 Inhibitor Linagliptin in Type 2 Diabetes (RENALIS)