Effects of Empagliflozin + Linagliptin vs Metformin + Insulin Glargine on Renal and Vascular Changes in Type 2 Diabetes

Sponsor
Institut für Pharmakologie und Präventive Medizin
Study ID
NCT02752113
Phase
PHASE3
Status
Completed

Conditions

  • Diabetes Mellitus Type 2

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

Study Details

Diabetes mellitus is a wide-spread disease accompanied by strongly increased morbidity and mortality due to micro- and macrovascular complications. However, in studies with patients suffering from diabetes mellitus type 2 (DM 2), early changes and impairments in large and small blood vessels as well as organ damage (e. g. to the kidneys) have been only insufficiently investigated (1). The newest substance class in oral antidiabetics, i. e. SGLT-2-inhibitors (such as empagliflozin) cause an increased renal excretion of glucose. In addition, the concurrent increased sodium excretion brings about an improvement of vascular function and thus a decrease in blood pressure. In the EMP-REG-OUTCOME study (2), the cardiovascular mortality rate was significantly lower in the empagliflozin group (3.7% versus 5.9%; 38% relative RR) compared to placebo.For another new substance class, the dipeptidylpeptidase-4-inhibitors, a number of pleiotropic effects have been described (3). In one of our recently conducted trials, we could demonstrate a positive effect of linagliptin on renal an inflammatory parameters compared to placebo (4). Thus, the combination of both substance classes with regard to positive effects on micro- and macrocirculation, even though not sufficiently proven as yet, suggests itself. The therapy with metformin and long-acting insulin (BOT), as well as a twofold oral medication is possible according to the recommendations of the "Deutsche Diabetes Gesellschaft (DDG)" and the positional paper of the "American Diabetes Association (ADA)". Accordingly, the aim of the present paper is the analysis of the effects of a combined therapy with empagliflozin plus linagliptin compared to metformin plus insulin glargine on renal and vascular changes in type 2 diabetes mellitus.

Key Dates

Start date
Apr 30, 2016
Status verified
Jul 2019
Primary completion
Nov 7, 2018
Completion
May 31, 2019

Study Design

Enrollment
101 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Empagliflozin and Linagliptin
    After the 4 weeks run-in phase (stable metformin medication), patients will be consecutively randomized (1:1) to empagliflozin 10 mg and linagliptin 5 mg orally once daily. After 14 days empagliflozin will be up-titrated to 25 mg (once daily), if fasting blood glucose is ≥ 100 mg /dl and no hypoglycemic symptoms are recognized.
  • Active Comparator: Metformin and Insulin sc
    Metformin p.o. and insulin sc After the 4 weeks run-in phase (stable metformin medication), patients will maintain on their metformin dosage (850 or 1000 mg orally twice daily) and insulin glargine (Lantus™) once daily subcutaneous will be added. Initially 2 - 4 U Lantus™ daily (depending on body weight) will be given, and adjusted every third day (telephone counseling) by adding 2 U if fasting blood glucose is not ≤ 125 mg/dl (16). After a stable dosage (i.e. no change of dosage for 1 week) has been reached, adjustments regarding an increment of Lantus™ will be based on confirmed fasting blood glucose of ≥ 126 mg/dl (on at least two consecutive day).

Primary Outcome Measure

Effect of empagliflozin plus linagliptin vs metformin plus insulin glargine on basal NO activity of renal vasculature (response of RPF (renal plasma flow) to L-NMMA (NG-monomethyl-L-arginine) infusion) [ Time Frame: at baseline and after 3 months on empagliflozin plus linagliptin or metformin plus insulin glargine, respectively ]

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