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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02752113
• Date of registration: 19/04/2016
• Prospective Registration: No
• Primary sponsor: Institut für Pharmakologie und Präventive Medizin
• Public title: Effects of Empagliflozin + Linagliptin vs Metformin + Insulin Glargine on Renal and Vascular Changes in Type 2 Diabetes ELMI
• Scientific title: ELMI - Prospective, Randomized, Controlled, Parallel-arm Study to Assess the Effects of the Combined Therapy of Empagliflozin and Linagliptin Compared to Metformin and Insulin Glargine on Renal and Vascular Changes in Type 2 Diabetes
• Date of first enrolment: April 2016
• Target sample size: 101
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02752113
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Germany

Contacts

• Name: Peter Bramlage, Prof MD
• Affiliation: IPPMed

• Name: Roland Schmieder, Prof MD
• Affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diabetes Mellitus Type 2

Intervention(s)

Drug: Empagliflozin and Linagliptin

Drug: Metformin and Insulin sc

Primary Outcome(s)

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]

Secondary Outcome(s)

changes in albuminuria (urinary albumin to creatinine ratio [UACR]), assessed in the 24-hour urine [Time Frame: at baseline and after three months]

changes in intraglomerular resistances (Ra and Re) and Pglom [Time Frame: at baseline and after three months]

Changes in oxidative stress level of renal vasculature (response of RPF to vitamin C infusion) [Time Frame: at baseline and after 3 months on empagliflozin plus linagliptin or metformin plus insulin glargine, respectively]

Secondary ID(s)

2016-000242-57

IPPMed-2016-01-ELMI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Erlangen-Nürnberg Medical School