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

• Status: Completed
• Trial end date: 2019-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut für Pharmakologie und Präventive Medizin
• Collaborator: University of Erlangen-Nürnberg Medical School
• Treatments: Empagliflozin; Insulin; Insulin Glargine; Insulin, Globin Zinc; Linagliptin; Metformin

Criteria

Inclusion Criteria:

• Type 2 diabetes mellitus, using already metformin (850 or 1000 mg twice daily) for at least 2 months prior to screening visit or type 2 diabetes switched to metformin at least 3 months prior to randomisation visit

• HbA1c ≥6.5 % if on antidiabetic montherapy or HbA1c ≥ 6.0 if on two antidiabetic drugs
• Age of 18 - 75 years

• Male and female patients (females of child bearing potential must be using adequate contraceptive precautions)

• Females of childbearing potential or within two years of the menopause must have a negative urine pregnancy test at screening visit

• Informed consent (§ 40 Abs. 1 Satz 3 Punkt 3 AMG) has to be given in written form.

Exclusion Criteria:

• Any other form of diabetes mellitus than type 2 diabetes mellitus

• Use of insulin, glitazone, gliptin or SGLT-2 inhibitor within the past 2 months

• HbA1c > 10.5% if on antidiabetic monotherapy and > 9.5% if on two antidiabetic drugs

• Fasting plasma glucose > 240 mg/dl

• Any history of stroke, transient ischemic attack, instable angina pectoris, or myocardial infarction within the last 6 months prior to study inclusion

• UACR ≥ 300 mg/g (early morning spot urine)

• Estimated GFR (eGFR) < 60 ml/min/1.73m²

• Uncontrolled arterial hypertension (blood pressure ≥ 180/110 mmHg)

• Congestive heart failure NYHA stage III and IV

• Severe disorders of the gastrointestinal tract or other diseases which interfere the pharmacodynamics and pharmacokinetics of study drugs

• Significant laboratory abnormalities such as serum Glutamate-Oxaloacetate-Transaminase (SGOT) or serum Glutamate-Pyruvate-Transaminase (SGPT) levels more than 3 x above the upper limit of normal range

• Drug or alcohol abuses

• Pregnant or breast-feeding patients

• Use of loop diuretics

• History of repetitive urogenital infection per year

• Body mass index > 40 kg/m²

• Triglyceride levels > 1000 mg/dl

• High density lipoprotein (HDL)-cholesterol levels < 25 mg/dl

• Any patient currently receiving chronic (>30 consecutive days) treatment with an oral corticosteroid

• Patients being treated for severe auto immune disease e.g. lupus

• Participation in another clinical study within 30 days prior to visit 1

• Individuals at risk for poor protocol or medication compliance

• Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V