Renal Actions of Combined Empagliflozin and LINagliptin in Type 2 diabetES

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The current study aims to explore the clinical effects and mechanistics of mono- and combination therapy with SGLT-2 inhibitor empagliflozin and DPP-4 inhibitor linagliptin on renal physiology and biomarkers in metformin-treated T2DM patients.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.H.H. Kramer
• Treatments: Empagliflozin; Gliclazide; Linagliptin

Criteria

Inclusion Criteria:

• Caucasian*

• Both genders (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L)

• Age: 35 - 75 years

• BMI: >25 kg/m2

• HbA1c: 7.0 - 9.5% Diabetes Control and Complications Trial (DCCT) or 53 - 80 mmol/mol International Federation of Clinical Chemistry (IFCC)

• Treatment with a stable dose of oral antihyperglycemic agents for at least 3 months prior to inclusion

• Metformin monotherapy

• Combination of metformin and low-dose SU derivative**

• Hypertension should be controlled, i.e. ≤140/90 mmHg, and treated with an ACE-I or ARB (unless prevented by adverse effect) for at least 3 months.

• Albuminuria should be treated with a RAAS-interfering agent (ACE-I or ARB) for at least 3 months.

• Written informed consent

• In order to increase homogeneity ** In order to accelerate inclusion, patients using combined metformin/SU derivative will be considered. In these patients, a 12 week wash-out period of the SU derivative will be observed, only when combined use has led to a HbA1c <8% at screening. Subsequently, patients will be eligible to enter the study, now using metformin monotherapy, provided that HbA1c still meets inclusion criteria.

Exclusion Criteria:

• Estimated GFR <45 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)

• Hemoglobin level < 7.0 mmol/L

• Current urinary tract infection and active nephritis

• History of unstable or rapidly progressing renal disease

• Macroalbuminuria; defined as ACR of >300 mg/g.

• Current/chronic use of the following medication: thiazolidinediones, sulfonylurea derivatives, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitor, oral glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MOAIs).

• Patients on diuretics will only be excluded when these drugs cannot be stopped 3 months prior randomization and for the duration of the study.

• Chronic use of non-steroidal anti-inflammatory drugs (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

• Pregnancy

• History of or actual severe mental disease

• History of or actual severe somatic disease (e.g. systemic disease)

• History of or actual malignancy (except basal cell carcinoma)

• History of or actual pancreatic disease

• (Unstable) thyroid disease

• Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN)

• Recent (<6 months) history of cardiovascular disease, including

• Acute coronary syndrome

• Stroke or transient ischemic neurologic disorder or chronic heart failure (NYHA grade II-IV)

• Complaints compatible with or established neurogenic bladder and/or incomplete bladder emptying (as determined by ultrasonic bladder scan)

• Substance abuse (alcohol: defined as >3 units alcohol/day)

• History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.

• Recent blood donation (< 6 months)

• Allergy to any of the agents used in the study

• Inability to understand the protocol and/or give informed consent

• 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