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

NCT ID: NCT02106104

Last Updated: 2016-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2016-04-30

Brief Summary

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.

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Linagliptin 5 mg QD (N=24)

Linagliptin 5 mg will be taken orally, once daily for 8 weeks

Group Type: EXPERIMENTAL

Linagliptin 5 mg QD (N=24)

Intervention Type: DRUG

Linagliptin 5 mg will be taken orally, once daily for 8 weeks

Glimepiride 1 mg QD (N=24)

Glimepiride 1 mg will be taken orally, once daily for 8 weeks

Group Type: ACTIVE_COMPARATOR

Glimepiride 1 mg QD (N=24)

Intervention Type: DRUG

Glimepiride 1 mg will be taken orally, once daily for 8 weeks

Interventions

Linagliptin 5 mg QD (N=24)

Linagliptin 5 mg will be taken orally, once daily for 8 weeks

Intervention Type: DRUG

Glimepiride 1 mg QD (N=24)

Glimepiride 1 mg will be taken orally, once daily for 8 weeks

Intervention Type: DRUG

Other Intervention Names

Trajenta; Amaryl

Eligibility 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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

M.H.H. Kramer

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Kramer, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

VU University Medical Center

Amsterdam, , Netherlands

Countries

Netherlands

References

Muskiet MHA, Tonneijck L, Smits MM, Kramer MHH, Ouwens DM, Hartmann B, Holst JJ, Touw DJ, Danser AHJ, Joles JA, van Raalte DH. Effects of DPP-4 Inhibitor Linagliptin Versus Sulfonylurea Glimepiride as Add-on to Metformin on Renal Physiology in Overweight Patients With Type 2 Diabetes (RENALIS): A Randomized, Double-Blind Trial. Diabetes Care. 2020 Nov;43(11):2889-2893. doi: 10.2337/dc20-0902. Epub 2020 Sep 8.

Reference Type: DERIVED

PMID: 32900785 (View on PubMed)

Other Identifiers

U1111-1143-9518

Identifier Type: OTHER

Identifier Source: secondary_id

2013-002493-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL47157.029.13

Identifier Type: REGISTRY

Identifier Source: secondary_id

DC2013RENALIS

Identifier Type: -

Identifier Source: org_study_id