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

Amsterdam UMC, location VUmc

Status and phase

Completed

Phase 4

Conditions

Type 2 Diabetes

Treatments

Drug: Glimepiride 1 mg QD (N=24)

Drug: Linagliptin 5 mg QD (N=24)

Study type

Interventional

Funder types

Other

Identifiers

NCT02106104

DC2013RENALIS

NL47157.029.13 (Registry Identifier)

2013-002493-47 (EudraCT Number)

U1111-1143-9518 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

48 patients

Sex

All

Ages

35 to 75 years old

Volunteers

No Healthy Volunteers

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