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

NCT ID: NCT04061200

Last Updated: 2019-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-01

Study Completion Date

2021-08-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 2 Diabetes With Renal Manifestations

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blinded

Study Groups

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Semaglutide 1,34 mg/ml

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.

Group Type ACTIVE_COMPARATOR

Semaglutide, 1.34 mg/mL

Intervention Type 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

Intervention Type OTHER

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

Empagliflozin 25 MG

Intervention Type 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

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.

Group Type PLACEBO_COMPARATOR

Semaglutide, 1.34 mg/mL

Intervention Type 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

Intervention Type OTHER

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

Empagliflozin 25 MG

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novo Nordisk A/S

INDUSTRY

Sponsor Role collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Steno Diabetes Center Copenhagen

Gentofte Municipality, , Denmark

Site Status

Countries

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Denmark

Central Contacts

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Peter Rossing, MD

Role: CONTACT

Suvanjaa Sivalingam

Role: CONTACT

References

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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.

Reference Type DERIVED
PMID: 39963952 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38770818 (View on PubMed)

Other Identifiers

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2019-003175-19

Identifier Type: -

Identifier Source: org_study_id

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