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

NCT04061200 | Unknown Phase 4 DMC

• 1 other identifier: 2019-003175-19
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes With Renal Manifestations

Outcome Measures

Primary Outcomes (1)

• Albuminuria

  Change in albuminuria

  From randomisation to week 52

Secondary Outcomes (5)

• Hba1c

  From randomisation to week 52

• GFR

  From randomisation to week 52

• 24 hour blood pressure

  From randomisation to week 52

• Vasoactive hormones

  From randomisation to week 52

• Inflammatory and endothelial biomarkers

  From randomisation to week 52

Study Arms (2)

Semaglutide 1,34 mg/ml

ACTIVE COMPARATOR

Semaglutide 1,34 mg/ml (solution for subcutaneous injection in pre-filled pen-injector). At randomisation, the participants start with doses of 0.25 mg/week for 4 weeks, then escalate to doses of 0.5 mg/week for 4 weeks, and thereafter escalate to 1.0 mg/week if tolerated until 52 weeks of total treatment.

Drug: Semaglutide, 1.34 mg/mL; Other: Placebo, 1,34 mg/mL; Drug: Empagliflozin 25 MG

Placebo 1,34 mg/ml

PLACEBO COMPARATOR

Placebo 1,34 mg/ml (solution for subcutaneous injection in pre-filled pen-injector). At randomisation, the participants start with doses of 0.25 mg/week for 4 weeks, then escalate to doses of 0.5 mg/week for 4 weeks, and thereafter escalate to 1.0 mg/week if tolerated until 52 weeks of total treatment.

Drug: Semaglutide, 1.34 mg/mL; Other: Placebo, 1,34 mg/mL; Drug: Empagliflozin 25 MG

Interventions

Semaglutide, 1.34 mg/mL DRUG

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.

Placebo 1,34 mg/ml; Semaglutide 1,34 mg/ml

Placebo, 1,34 mg/mL OTHER

Participants will be randomised to either semaglutide or placebo as an add on treatment after 26 weeks of intervention with empagliflozin 25 mg.

Placebo 1,34 mg/ml; Semaglutide 1,34 mg/ml

Empagliflozin 25 MG DRUG

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.

Placebo 1,34 mg/ml; Semaglutide 1,34 mg/ml

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Given written informed consent
• Male or female patients ≥ 18 years with type 2 diabetes (WHO criteria).
• UACR \> 100 mg/g within a year of informed consent documented in the medical files.
• 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.
• 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
• 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.
• Ability to communicate with the investigator and understand informed consent.

You may not qualify if:

• Type 1 diabetes
• Known or suspected hypersensitivity to trial product(s) or related products
• 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
• 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.
• Previous bowel resection
• Body mass index \< 18.5 kg/m2
• Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
• Known or suspected abuse of alcohol or narcotics.
• Participant in another intervention study

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

Related Publications (2)

• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

  PMID: 39963952 DERIVED

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

MeSH Terms

Interventions

semaglutide; empagliflozin

Central Study Contacts

Peter Rossing, MD

CONTACT

30912975; peter.rossing@regionh.dk

Suvanjaa Sivalingam

CONTACT

24405599; suvanjaa.sivalingam.02@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 19, 2019
• Study Start: November 1, 2019
• Primary Completion: July 1, 2021
• Study Completion: August 1, 2021
• Last Updated: August 19, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)