Renal Effects of Treatment With Empagliflozin Alone or in Combination With Semaglutide in Patients With Type 2 Diabetes and Albuminuria

Type 2 Diabetes With Renal Manifestations Clinical Trial

— EmpaSema  

Official title:

Renal Effects of Treatment With Empagliflozin Alone or in Combination With Semaglutide in Patients With Type 2 Diabetes and Albuminuria - A Double Blinded, Randomised, Placebo Controlled, Parallel, Single Center Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04061200
• Other study ID #: 2019-003175-19
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: November 1, 2019
• Est. completion date: August 1, 2021

Study information

• Verified date: August 2019
• Source: Steno Diabetes Center Copenhagen
• Contact: Peter Rossing, MD
• Phone: 30912975
• Email: peter.rossing[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the effect of treatment with semaglutide 1.34 mg/ml in combination with empagliflozin 25 mg, compared to treatment with empagliflozin 25 mg in combination with placebo on albuminuria in participants with type 2 diabetes and albuminuria.

In a randomised, placebo-controlled, double-blinded, parallel trial we will include 80 patients with type 2 diabetes and albuminuria. Patients will start in a run-in phase of 26 weeks with empagliflozin 25 mg alone. After that, the patients will be randomised 1:1 to an active treatment period with semaglutide of 26 weeks or placebo for 26 weeks.

The primary endpoint is change from randomisation to week 52 in albuminuria, measured in three morning urine samples.

Description:

Patients with type 2 diabetes are at high risk of developing diabetic nephropathy. The most promising antidiabetic agents on the market with potential to preserve renal function are endogenous glucagon like peptide (GLP-1) agonists and selective sodium-glucose cotransporter 2 (SGLT2) inhibitors. The LEADER trial demonstrated that treatment with liraglutide (GLP-1 agonist) resulted in 22% lower risk of renal composite outcome. The EMPA-REG trial demonstrated that treatment with empagliflozin (SGLT2 inhibitor) reduced the same renal composite outcome by 39%.

Previous studies have mainly focused on glycaemic parameters when combining a GLP-1 agonist and SGLT2 inhibitor. From a renal perspective, it is of major interest to investigate if a stepwise initiation of semaglutide or placebo added to ongoing empagliflozin therapy would complement or have an additive effect on renal parameters.

In a randomised, placebo-controlled, double-blinded, parallel trial we will include 80 patients with type 2 diabetes and albuminuria. Patients will start in a run-in phase of 26 weeks with empagliflozin 25 mg alone. After that, the patients will be randomised 1:1 to an active treatment period with semaglutide of 26 weeks or placebo for 26 weeks.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: August 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Given written informed consent

2. Male or female patients = 18 years with type 2 diabetes (WHO criteria).

3. UACR > 100 mg/g within a year of informed consent documented in the medical files.

4. eGFR = 30 ml/min/1.73 m2 (estimated by CKD-EPI formula) within 3 months of informed consent documented in the medical files. The eGFR measured at visit 0 has to meet the criteria as well.

5. Fertile female must use chemical, hormonal and mechanical contraceptives, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening

6. Treated with maximal tolerated dose of an angiotensin-converting-enzyme inhibitor or an angiotensin II receptor blocker, 4 weeks prior to randomisation. If the participants are not treated with maximal tolerated dosis the investigator will increase the dose 4 weeks prior randomisation if tolerated.

7. Ability to communicate with the investigator and understand informed consent.

Exclusion Criteria:

1. Type 1 diabetes

2. Known or suspected hypersensitivity to trial product(s) or related products

3. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial

4. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months.

5. Previous bowel resection

6. Body mass index < 18.5 kg/m2

7. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods

8. Known or suspected abuse of alcohol or narcotics.

9. Participant in another intervention study

Related Conditions & MeSH terms

• Albuminuria
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Type 2 Diabetes With Renal Manifestations

Intervention

Drug:
• Semaglutide, 1.34 mg/mL
After informed consent, subjects will be initiated on open-label empagliflozin 25 mg or maximal tolerated dosis once daily during a run-in period of 26 weeks. Participants will be randomized and up titrated to semaglutide 1.34 mg/ml or matching placebo once weekly during the following 26 weeks in a 1:1 ratio.

Other:
• Placebo, 1,34 mg/mL
Participants will be randomised to either semaglutide or placebo as an add on treatment after 26 weeks of intervention with empagliflozin 25 mg.

Drug:
• Empagliflozin 25 MG
After informed consent, subjects will be initiated on open-label empagliflozin 25 mg or maximal tolerated dosis once daily during a run-in period of 26 weeks.

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Copenhagen	Gentofte

Sponsors (2)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Albuminuria	Change in albuminuria	From randomisation to week 52
Secondary	Hba1c	Change in Hba1c	From randomisation to week 52
Secondary	GFR	Change in measured kidney function (GFR)	From randomisation to week 52
Secondary	24 hour blood pressure	Change in 24 hour blood pressure	From randomisation to week 52
Secondary	Vasoactive hormones	Change in vasoactive hormones (o Plasma renin concentration, plasma renin activity, angiotensin I, angiotensin II, aldosterone, copeptin)	From randomisation to week 52
Secondary	Inflammatory and endothelial biomarkers	Change in inflammatory and endothelial biomarkers (Von Willebrand factor, sVCAM-1, sICAM-1, E-selectin, b-leucocytes, s-CRP, IL-6, osteopontin, TNF-a)	From randomisation to week 52