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)

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) - RENALIS: RENoprotection in diAbetes by LInagliptin versus Sulfonylurea

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON41714

Enrollment

Registered

2013-12-11

Start date

2014-05-14

Completion date

Unknown

Last updated

2024-04-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Interventions

Subjects will be randomized to either of the following arms: Treatment arm 1: Linagliptin 5 mg oral once daily Treatment arm 2: Glimepiride 1 mg oral once daily

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: * Caucasian * Male and Female (must be post-menopausal; no menses >1 year) * Age: 35 - 75 years * BMI: >25 kg/m2 * Type 2 diabetes mellitus (HbA1c: 6.5 - 9% DCCT or 48 - 75 mmol/mol IFCC) who are being treated with a stable dose of oral antihyperglycemic agents (metformin monotherapy or combination of metformin and low dose SU derivative) for at least 3 months prior to inclusion * All patients with previously diagnosed hypertension should use a RAS-interfering agent (ACE-i / ARB) for at least 3 months

Exclusion criteria

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 (i.e. sports injury, head-ache or back ache). However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing * Estimated Glomerular Filtration Rate 4 units/day) * Allergy to any of the agents used in the study * Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study * Inability to understand the study protocol or give informed consent

Design outcomes

Primary

Measure	Time frame
Renal hemodynamics, measured as: * Glomerular filtration rate (GFR; measured by the inulin-clearance technique) * Effective renal plasma flow (ERPF; measured by the para-aminohippuric acid (PAH) clearance technique)	—

Secondary

Measure	Time frame
To assess changes from baseline following 8-week treatment with a DPP-4i versus SU derivative on: * Systolic and diastolic blood pressure, mean arterial pressure * Heart rate * Renal tubular function, measured as: o Fractional sodium- and urea excretion o Urine osmolality * Renal damage, measured by urine biomarkers as: o Albumin/creatinine-ratio (Glomerular) o NGAL and KIM1 (Tubular) Exploratory Objectives Resting heart rate variability * Cardiac autonomic nervous system function * Systemic hemodynamic variables * Microvascular function * Arterial stiffness * Glycemic variables * Lipid spectrum * Biomarkers * Plasma DPP4- and ACE activity * Body anthropometrics * Body fat content	—

Measure

Time frame

To assess changes from baseline following 8-week treatment with a DPP-4i versus SU derivative on: * Systolic and diastolic blood pressure, mean arterial pressure * Heart rate * Renal tubular function, measured as: o Fractional sodium- and urea excretion o Urine osmolality * Renal damage, measured by urine biomarkers as: o Albumin/creatinine-ratio (Glomerular) o NGAL and KIM*1 (Tubular) Exploratory Objectives * Resting heart rate variability * Cardiac autonomic nervous system function * Systemic hemodynamic variables * Microvascular function * Arterial stiffness * Glycemic variables * Lipid spectrum * Biomarkers * Plasma DPP4- and ACE activity * Body anthropometrics * Body fat content

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)